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A Study of Olaratumab (LY3012207) in Participants With Advanced Soft Tissue Sarcoma (ANNOUNCE 2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02659020
Recruitment Status : Completed
First Posted : January 20, 2016
Results First Posted : October 11, 2021
Last Update Posted : October 27, 2021
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Soft Tissue Sarcoma
Interventions Drug: Olaratumab
Drug: Gemcitabine
Drug: Docetaxel
Drug: Placebo
Enrollment 310
Recruitment Details  
Pre-assignment Details Completers included participants who died from any cause.
Arm/Group Title Phase 1b: Cohort 1 - 15 mg/kg Olaratumab + Gemcitabine + Docetaxel Phase 1b: Cohort 2 - 20 mg/kg Olaratumab + Gemcitabine + Docetaxel Phase 1b: Cohort 2 Expansion - 20 mg/kg Olaratumab + Gemcitabine + Docetaxel Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab-naive) Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab Pre-treated) Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab-naive) Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab Pre-treated)
Hide Arm/Group Description Participants received intravenous infusions of olaratumab 15 milligrams per kilogram (mg/kg) on days 1, 8 plus gemcitabine 900 milligrams per meter square (mg/m^2) on days 1, 8 plus docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met. Participants received intravenous infusions of olaratumab 20 mg/kg on days 1, 8 in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met. Following a protocol amendment, additional participants were enrolled into this group to confirm the safety of the 20 mg/kg dose level prior to opening the Phase 2. Participants received intravenous infusions of olaratumab 20 milligrams per kilogram (mg/kg) on days 1, 8 plus gemcitabine 900 milligrams per meter square (mg/m^2) on days 1, 8 plus docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met. This cohort included participants who never received olaratumab prior to enrollment. Participants received intravenous infusions of olaratumab loading dose 20 mg/kg on days 1, 8 of cycle 1 followed by 15 mg/kg on days 1, 8 of all subsequent cycles in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met. This cohort included participants who received commercially available olaratumab prior to enrollment. Participants received intravenous infusions of olaratumab loading dose 20 mg/kg on days 1, 8 of cycle 1 followed by 15 mg/kg on days 1, 8 of all subsequent cycles in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met. This cohort included participants who never received olaratumab prior to enrollment. Participants received intravenous infusions of placebo on days 1, 8 in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met. This cohort included participants who received commercially available olaratumab prior to enrollment. Participants received intravenous infusions of placebo on days 1, 8 in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.
Period Title: Overall Study
Started 21 18 15 81 46 86 43
Received at Least 1 Dose of Study Drug 21 18 15 81 45 86 43
Completed 15 11 10 51 26 58 28
Not Completed 6 7 5 30 20 28 15
Reason Not Completed
Adverse Event             1             0             0             6             3             4             4
Lost to Follow-up             1             2             1             4             1             5             0
Physician Decision             0             0             1             1             6             3             1
Withdrawal by Subject             2             3             1             4             4             9             3
Progressive Disease             2             2             2             15             6             7             6
On Treatment             0             0             0             0             0             0             1
Arm/Group Title Phase 1b: Cohort 1 - 15 mg/kg Olaratumab + Gemcitabine + Docetaxel Phase 1b: Cohort 2 - 20 mg/kg Olaratumab + Gemcitabine + Docetaxel Phase 1b: Cohort 2 Expansion - 20 mg/kg Olaratumab + Gemcitabine + Docetaxel Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab-naive) Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab Pre-treated) Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab-naive) Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab Pre-treated) Total
Hide Arm/Group Description Participants received intravenous infusions of olaratumab 15 milligrams per kilogram (mg/kg) on days 1, 8 plus gemcitabine 900 milligrams per meter square (mg/m^2) on days 1, 8 plus docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met. Participants received intravenous infusions of olaratumab 20 mg/kg on days 1, 8 in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met. Following a protocol amendment, additional participants were enrolled into this group to confirm the safety of the 20 mg/kg dose level prior to opening the Phase 2. Participants received intravenous infusions of olaratumab 20 milligrams per kilogram (mg/kg) on days 1, 8 plus gemcitabine 900 milligrams per meter square (mg/m^2) on days 1, 8 plus docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met. This cohort included participants who never received olaratumab prior to enrollment. Participants received intravenous infusions of olaratumab loading dose 20 mg/kg on days 1, 8 of cycle 1 followed by 15 mg/kg on days 1, 8 of all subsequent cycles in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met. This cohort included participants who received commercially available olaratumab prior to enrollment. Participants received intravenous infusions of olaratumab loading dose 20 mg/kg on days 1, 8 of cycle 1 followed by 15 mg/kg on days 1, 8 of all subsequent cycles in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met. This cohort included participants who never received olaratumab prior to enrollment. Participants received intravenous infusions of placebo on days 1, 8 in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met. This cohort included participants who received commercially available olaratumab prior to enrollment. Participants received intravenous infusions of placebo on days 1, 8 in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met. Total of all reporting groups
Overall Number of Baseline Participants 21 18 15 81 46 86 43 310
Hide Baseline Analysis Population Description
All participants from phase 1b/2.
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 21 participants 18 participants 15 participants 81 participants 46 participants 86 participants 43 participants 310 participants
<65 years 20 12 6 66 27 66 30 227
>=65 years 1 6 9 15 19 20 13 83
<=18 years 0 0 0 0 0 0 0 0
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 21 participants 18 participants 15 participants 81 participants 46 participants 86 participants 43 participants 310 participants
Female 11 8 7 48 28 58 28 188
Male 10 10 8 33 18 28 15 122
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 21 participants 18 participants 15 participants 81 participants 46 participants 86 participants 43 participants 310 participants
Hispanic or Latino 5 0 1 8 4 6 4 28
Not Hispanic or Latino 16 18 11 71 39 73 36 264
Unknown or Not Reported 0 0 3 2 3 7 3 18
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 21 participants 18 participants 15 participants 81 participants 46 participants 86 participants 43 participants 310 participants
American Indian or Alaska Native 0 0 1 0 0 0 0 1
Asian 0 1 1 3 2 2 2 11
Native Hawaiian or Other Pacific Islander 0 0 0 0 1 0 0 1
Black or African American 0 2 0 1 8 1 2 14
White 15 10 13 61 30 70 34 233
More than one race 6 5 0 15 3 10 3 42
Unknown or Not Reported 0 0 0 1 2 3 2 8
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 21 participants 18 participants 15 participants 81 participants 46 participants 86 participants 43 participants 310 participants
Hungary 0 0 0 5 0 6 0 11
United States 10 14 14 29 36 28 30 161
Poland 0 0 0 6 0 2 0 8
United Kingdom 0 0 0 11 3 12 5 31
Italy 0 0 0 2 0 4 0 6
Israel 0 0 0 4 3 7 4 18
France 0 0 0 2 0 3 0 5
Australia 0 0 1 6 0 2 0 9
Germany 0 0 0 7 4 11 2 24
Spain 11 4 0 9 0 11 2 37
1.Primary Outcome
Title Phase 1b: Number of Participants With Dose Limiting Toxicity (DLT)
Hide Description

A Dose Limiting Toxicity is defined as an Adverse Event (AE) that is likely related to the study medication or combination, and fulfils any one of the following criteria, graded according to the NCI-CTCAE Version 4.0:

  1. Febrile neutropenia with documented Grade ≥3 infection or sepsis
  2. Grade 4 neutropenia lasting 7 days or longer.
  3. Grade 4 thrombocytopenia, or Grade 3 thrombocytopenia complicated by hemorrhage.
  4. Nonhematologic Grade ≥3 toxicity, except for toxicities such as nausea, vomiting, transient electrolyte abnormalities, or diarrhoea that can be controlled with optimal medical management within 48 hours.
Time Frame Cycle 1 (Up To 21 Days)
Hide Outcome Measure Data
Hide Analysis Population Description
Phase 1b: All participants who received at least one dose of Olaratumab.
Arm/Group Title Phase 1b: Cohort 1 - 15 mg/kg Olaratumab + Gemcitabine + Docetaxel Phase 1b: Cohort 2 - 20 mg/kg Olaratumab + Gemcitabine + Docetaxel Phase 1b: Cohort 2 Expansion - 20 mg/kg Olaratumab + Gemcitabine + Docetaxel
Hide Arm/Group Description:
Participants received intravenous infusions of olaratumab 15 milligrams per kilogram (mg/kg) on days 1, 8 plus gemcitabine 900 milligrams per meter square (mg/m^2) on days 1, 8 plus docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.
Participants received intravenous infusions of olaratumab 20 mg/kg on days 1, 8 in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.
Following a protocol amendment, additional participants were enrolled into this group to confirm the safety of the 20 mg/kg dose level prior to opening the Phase 2. Participants received intravenous infusions of olaratumab 20 milligrams per kilogram (mg/kg) on days 1, 8 plus gemcitabine 900 milligrams per meter square (mg/m^2) on days 1, 8 plus docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.
Overall Number of Participants Analyzed 21 18 15
Measure Type: Count of Participants
Unit of Measure: Participants
1 4 3
2.Primary Outcome
Title Phase 2: Overall Survival (OS) (Olaratumab-Naive)
Hide Description OS was defined as the time from the date of randomization to the date of death from any cause. For each participant who is not known to have died as of the data-inclusion cut-off date for a particular analysis, overall survival duration was censored for that analysis at the date of last prior contact.
Time Frame Baseline to Date of Death Due to Any Cause (Up To 38 Months)
Hide Outcome Measure Data
Hide Analysis Population Description
Phase 2: All randomized participants (including the censored participants). Number of participants censored in "Olaratumab + Gemcitabine + Docetaxel (Olaratumab-naive) =30," "Placebo + Gemcitabine + Docetaxel (Olaratumab-naive) =28."
Arm/Group Title Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab-naive) Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab-naive)
Hide Arm/Group Description:
This cohort included participants who never received olaratumab prior to enrollment. Participants received intravenous infusions of olaratumab loading dose 20 mg/kg on days 1, 8 of cycle 1 followed by 15 mg/kg on days 1, 8 of all subsequent cycles in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.
This cohort included participants who never received olaratumab prior to enrollment. Participants received intravenous infusions of placebo on days 1, 8 in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.
Overall Number of Participants Analyzed 81 86
Median (95% Confidence Interval)
Unit of Measure: Months
16.76
(15.28 to 25.40)
18.04
(13.17 to 22.90)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab-naive), Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab-naive)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.775
Comments Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and Eastern Cooperative Oncology Group Performance Status (ECOG PS) (0 vs1).
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.945
Confidence Interval (2-Sided) 95%
0.639 to 1.397
Estimation Comments Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).
3.Secondary Outcome
Title Phase 1b: Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of Olaratumab
Hide Description Cmax of Olaratumab.
Time Frame Pre-dose, 5 minutes (min), 1, 4, 4.5, 24, 96, 168, 336 hours (h) post-dose on Cycle 1 Day 1, Cycle 1 Day 8, Cycle 3 Day 1, Cycle 3 Day 8
Hide Outcome Measure Data
Hide Analysis Population Description
Phase 1b: All participants who received at least one dose of Olaratumab and had evaluable PK data.
Arm/Group Title Phase 1b: Cohort 1 - 15 mg/kg Olaratumab + Gemcitabine + Docetaxel Phase 1b: Cohort 2 Overall - 20 mg/kg Olaratumab + Gemcitabine + Docetaxel
Hide Arm/Group Description:
Participants received intravenous infusions of olaratumab 15 milligrams per kilogram (mg/kg) on days 1, 8 plus gemcitabine 900 milligrams per meter square (mg/m^2) on days 1, 8 plus docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.
Participants received intravenous infusions of olaratumab 20 mg/kg on days 1, 8 in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met (cohort 2). Following a protocol amendment, additional participants were enrolled into this group to confirm the safety of the 20 mg/kg dose level prior to opening the Phase 2 (cohort 2 expansion).
Overall Number of Participants Analyzed 20 33
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: micrograms per milliliter (μg/mL)
Cycle 1 (Day 1) Number Analyzed 19 participants 33 participants
432
(24%)
572
(25%)
Cycle 1 (Day 8) Number Analyzed 20 participants 33 participants
460
(25%)
697
(20%)
Cycle 3 (Day 1) Number Analyzed 14 participants 23 participants
523
(38%)
644
(20%)
Cycle 3 (Day 8) Number Analyzed 14 participants 22 participants
513
(21%)
689
(20%)
4.Secondary Outcome
Title Phase 1b: PK: Minimum Serum Concentration (Cmin) of Olaratumab
Hide Description Cmin of Olaratumab.
Time Frame Pre-dose, 5 min, 1, 4, 4.5, 24, 96, 168, 336 h post-dose on Cycle 1 Day 1, Cycle 1 Day 8, Cycle 3 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
Phase 1b: All participants who received at least one dose of Olaratumab and had evaluable PK data.
Arm/Group Title Phase 1b: Cohort 1 - 15 mg/kg Olaratumab + Gemcitabine + Docetaxel Phase 1b: Cohort 2 Overall - 20 mg/kg Olaratumab + Gemcitabine + Docetaxel
Hide Arm/Group Description:
Participants received intravenous infusions of olaratumab 15 milligrams per kilogram (mg/kg) on days 1, 8 plus gemcitabine 900 milligrams per meter square (mg/m^2) on days 1, 8 plus docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.
Participants received intravenous infusions of olaratumab 20 mg/kg on days 1, 8 in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met (cohort 2). Following a protocol amendment, additional participants were enrolled into this group to confirm the safety of the 20 mg/kg dose level prior to opening the Phase 2 (cohort 2 expansion).
Overall Number of Participants Analyzed 20 31
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: μg/mL
Cycle 1 (Day 1) Number Analyzed 20 participants 31 participants
95.9
(37%)
142
(38%)
Cycle 1 (Day 8) Number Analyzed 19 participants 30 participants
64.3
(64%)
93.3
(47%)
Cycle 3 (Day 1) Number Analyzed 14 participants 22 participants
137
(40%)
252
(36%)
5.Secondary Outcome
Title Phase 1b: PK: Elimination Half-Life (T1/2) of Olaratumab
Hide Description T1/2 of Olaratumab.
Time Frame Pre-dose, 5 min, 1, 4, 4.5, 24, 96, 168, 336 h post-dose on Cycle 1 Day 1, Cycle 1 Day 8, Cycle 3 Day 1, Cycle 3 Day 8
Hide Outcome Measure Data
Hide Analysis Population Description
Phase 1b: All participants who received at least one dose of Olaratumab and had evaluable PK data.
Arm/Group Title Phase 1b: Cohort 1 - 15 mg/kg Olaratumab + Gemcitabine + Docetaxel Phase 1b: Cohort 2 Overall - 20 mg/kg Olaratumab + Gemcitabine + Docetaxel
Hide Arm/Group Description:
Participants received intravenous infusions of olaratumab 15 milligrams per kilogram (mg/kg) on days 1, 8 plus gemcitabine 900 milligrams per meter square (mg/m^2) on days 1, 8 plus docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.
Participants received intravenous infusions of olaratumab 20 mg/kg on days 1, 8 in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met (cohort 2). Following a protocol amendment, additional participants were enrolled into this group to confirm the safety of the 20 mg/kg dose level prior to opening the Phase 2 (cohort 2 expansion).
Overall Number of Participants Analyzed 19 33
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: days
Cycle 1 (Day 1) Number Analyzed 19 participants 33 participants
4.60
(34%)
4.29
(28%)
Cycle 1 (Day 8) Number Analyzed 19 participants 33 participants
6.25
(25%)
6.62
(27%)
Cycle 3 (Day 1) Number Analyzed 14 participants 23 participants
5.17
(36%)
6.36
(41%)
Cycle 3 (Day 8) Number Analyzed 14 participants 21 participants
5.82
(30%)
6.39
(32%)
6.Secondary Outcome
Title Phase 1b/2: PK: Cmax of Gemcitabine
Hide Description Cmax of Gemcitabine.
Time Frame Day 8 of Cycle 1 (end of infusion, 1, 2, 4, 24 hours post-infusion)
Hide Outcome Measure Data
Hide Analysis Population Description
Phase 1b/2: All participants who received at least one dose of Gemcitabine and had evaluable PK data.
Arm/Group Title Phase 1b: Cohort 1 - 15 mg/kg Olaratumab + Gemcitabine + Docetaxel Phase 1b: Cohort 2 Overall - 20 mg/kg Olaratumab + Gemcitabine + Docetaxel Phase 2: Olaratumab + Gemcitabine + Docetaxel Phase 2: Placebo + Gemcitabine + Docetaxel
Hide Arm/Group Description:
Participants received intravenous infusions of olaratumab 15 milligrams per kilogram (mg/kg) on days 1, 8 plus gemcitabine 900 milligrams per meter square (mg/m^2) on days 1, 8 plus docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.
Participants received intravenous infusions of olaratumab 20 mg/kg on days 1, 8 in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met (cohort 2). Following a protocol amendment, additional participants were enrolled into this group to confirm the safety of the 20 mg/kg dose level prior to opening the Phase 2 (cohort 2 expansion).
Participants received intravenous infusions of olaratumab loading dose 20 mg/kg on days 1, 8 of cycle 1 followed by 15 mg/kg on days 1, 8 of all subsequent cycles in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met. This cohort is a combination of participants who never received olaratumab (olaratumab-naive) and who received commercially available olaratumab (olaratumab pre-treated) prior to enrollment.
Participants received intravenous infusions of placebo on days 1, 8 in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met. This cohort is a combination of participants who never received olaratumab (olaratumab-naive) and who received commercially available olaratumab (olaratumab pre-treated) prior to enrollment.
Overall Number of Participants Analyzed 18 24 87 88
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: μg/mL
2.79
(70%)
3.49
(50%)
3.01
(122%)
2.35
(105%)
7.Secondary Outcome
Title Phase 1b/2: PK: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC[0-∞]) of Gemcitabine
Hide Description AUC[0-∞] of Gemcitabine
Time Frame Day 8 of Cycle 1 (end of infusion, 1, 2, 4, 24 hours post-infusion)
Hide Outcome Measure Data
Hide Analysis Population Description
Phase 1b/2: Zero participants analysed. Due to short half-life of Gemcitabine, there was insufficient quantifiable data in the elimination phase to calculate AUC[0-∞] for any of the participants.
Arm/Group Title Phase 1b: Cohort 1 - 15 mg/kg Olaratumab + Gemcitabine + Docetaxel Phase 1b: Cohort 2 Overall - 20 mg/kg Olaratumab + Gemcitabine + Docetaxel Phase 2: Olaratumab + Gemcitabine + Docetaxel Phase 2: Placebo + Gemcitabine + Docetaxel
Hide Arm/Group Description:
Participants received intravenous infusions of olaratumab 15 milligrams per kilogram (mg/kg) on days 1, 8 plus gemcitabine 900 milligrams per meter square (mg/m^2) on days 1, 8 plus docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.
Participants received intravenous infusions of olaratumab 20 mg/kg on days 1, 8 in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met (cohort 2). Following a protocol amendment, additional participants were enrolled into this group to confirm the safety of the 20 mg/kg dose level prior to opening the Phase 2 (cohort 2 expansion).
Participants received intravenous infusions of olaratumab loading dose 20 mg/kg on days 1, 8 of cycle 1 followed by 15 mg/kg on days 1, 8 of all subsequent cycles in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met. This cohort is a combination of participants who never received olaratumab (olaratumab-naive) and who received commercially available olaratumab (olaratumab pre-treated) prior to enrollment.
Participants received intravenous infusions of placebo on days 1, 8 in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met. This cohort is a combination of participants who never received olaratumab (olaratumab-naive) and who received commercially available olaratumab (olaratumab pre-treated) prior to enrollment.
Overall Number of Participants Analyzed 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
8.Secondary Outcome
Title Phase 1b/2: PK: Cmax of Docetaxel
Hide Description Cmax of Docetaxel.
Time Frame 5 min, 1, 3, 24, 48 h post-dose on Cycle 1 Day 8
Hide Outcome Measure Data
Hide Analysis Population Description
Phase 1b/2: All participants who received at least one dose of Docetaxel and had evaluable PK data.
Arm/Group Title Phase 1b: Cohort 1 - 15 mg/kg Olaratumab + Gemcitabine + Docetaxel Phase 1b: Cohort 2 Overall - 20 mg/kg Olaratumab + Gemcitabine + Docetaxel Phase 2: Olaratumab + Gemcitabine + Docetaxel Phase 2: Placebo + Gemcitabine + Docetaxel
Hide Arm/Group Description:
Participants received intravenous infusions of olaratumab 15 milligrams per kilogram (mg/kg) on days 1, 8 plus gemcitabine 900 milligrams per meter square (mg/m^2) on days 1, 8 plus docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.
Participants received intravenous infusions of olaratumab 20 mg/kg on days 1, 8 in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met (cohort 2). Following a protocol amendment, additional participants were enrolled into this group to confirm the safety of the 20 mg/kg dose level prior to opening the Phase 2 (cohort 2 expansion).
Participants received intravenous infusions of olaratumab loading dose 20 mg/kg on days 1, 8 of cycle 1 followed by 15 mg/kg on days 1, 8 of all subsequent cycles in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met. This cohort is a combination of participants who never received olaratumab (olaratumab-naive) and who received commercially available olaratumab (olaratumab pre-treated) prior to enrollment.
Participants received intravenous infusions of placebo on days 1, 8 in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met. This cohort is a combination of participants who never received olaratumab (olaratumab-naive) and who received commercially available olaratumab (olaratumab pre-treated) prior to enrollment.
Overall Number of Participants Analyzed 18 30 71 73
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Nanograms per milliliter
903
(143%)
1110
(84%)
1030
(134%)
827
(102%)
9.Secondary Outcome
Title Phase 1b/2: PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC [0-∞]) of Docetaxel
Hide Description AUC [0-∞] of Docetaxel.
Time Frame 5 min, 1, 3, 24, 48 h post-dose on Cycle 1 Day 8
Hide Outcome Measure Data
Hide Analysis Population Description
Phase 1b/2: All participants who received at least one dose of Docetaxel and had evaluable PK data. For phase 2, zero participants analysed due to data not collected for AUC [0-∞] of Docetaxel.
Arm/Group Title Phase 1b: Cohort 1 - 15 mg/kg Olaratumab + Gemcitabine + Docetaxel Phase 1b: Cohort 2 Overall - 20 mg/kg Olaratumab + Gemcitabine + Docetaxel Phase 2: Olaratumab + Gemcitabine + Docetaxel Phase 2: Placebo + Gemcitabine + Docetaxel
Hide Arm/Group Description:
Participants received intravenous infusions of olaratumab 15 milligrams per kilogram (mg/kg) on days 1, 8 plus gemcitabine 900 milligrams per meter square (mg/m^2) on days 1, 8 plus docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.
Participants received intravenous infusions of olaratumab 20 mg/kg on days 1, 8 in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met (cohort 2). Following a protocol amendment, additional participants were enrolled into this group to confirm the safety of the 20 mg/kg dose level prior to opening the Phase 2 (cohort 2 expansion).
Participants received intravenous infusions of olaratumab loading dose 20 mg/kg on days 1, 8 of cycle 1 followed by 15 mg/kg on days 1, 8 of all subsequent cycles in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met. This cohort is a combination of participants who never received olaratumab (olaratumab-naive) and who received commercially available olaratumab (olaratumab pre-treated) prior to enrollment.
Participants received intravenous infusions of placebo on days 1, 8 in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met. This cohort is a combination of participants who never received olaratumab (olaratumab-naive) and who received commercially available olaratumab (olaratumab pre-treated) prior to enrollment.
Overall Number of Participants Analyzed 7 18 0 0
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanograms*hours per milliliter
4440
(103%)
2990
(83%)
10.Secondary Outcome
Title Phase 1b/2: Population PK: Clearance of Olaratumab
Hide Description Population PK: Clearance of Olaratumab
Time Frame Cycle 1-19: Pre-dose, 5 min, 1, 4, 4.5, 24, 96, 168, 336 h post-dose on days 1, 8
Hide Outcome Measure Data
Hide Analysis Population Description
Phase 1b/2: All participants who received at least one dose of Olaratumab and had evaluable PK data. Phase 1b and phase 2 participants olaratumab PK data was planned to be pooled for the population PK analysis and compared to a validated PK model to confirm that PK parameters were similar to analyses from previous olaratumab studies.
Arm/Group Title Olaratumab + Gemcitabine + Docetaxel
Hide Arm/Group Description:
Participants received intravenous infusions of olaratumab on days 1, 8 (phase 1: 15 or 20 mg/kg; phase 2: 20 mg/kg only in cycle 1 and 15 mg/kg in subsequent cycles) plus gemcitabine 900 mg/m^2 on days 1, 8 plus docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.
Overall Number of Participants Analyzed 178
Mean (95% Confidence Interval)
Unit of Measure: Liter Per Hour
0.0186
(0.0175 to 0.0192)
11.Secondary Outcome
Title Phase 1b/2: Population PK: Volume of Distribution at Steady State (Vss) of Olaratumab
Hide Description The Vss is the sum of central volume of distribution (V1) + peripheral volume of distribution (V2).
Time Frame Cycle 1-19: Pre-dose, 5 min, 1, 4, 4.5, 24, 96, 168, 336 h post-dose on days 1, 8
Hide Outcome Measure Data
Hide Analysis Population Description
Phase 1b/2: All participants who received at least one dose of Olaratumab and had evaluable PK data. Phase 1b and phase 2 participants olaratumab PK data was planned to be pooled for the population PK analysis and compared to a validated PK model to confirm that PK parameters were similar to analyses from previous olaratumab studies.
Arm/Group Title Olaratumab + Gemcitabine + Docetaxel
Hide Arm/Group Description:
Participants received intravenous infusions of olaratumab on days 1, 8 (phase 1: 15 or 20 mg/kg; phase 2: 20 mg/kg only in cycle 1 and 15 mg/kg in subsequent cycles) plus gemcitabine 900 mg/m^2 on days 1, 8 plus docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.
Overall Number of Participants Analyzed 178
Mean (95% Confidence Interval)
Unit of Measure: Liter
5.14
(4.68 to 5.54)
12.Secondary Outcome
Title Phase 2: Overall Survival (Olaratumab Pre-Treated)
Hide Description OS was defined as the time from the date of randomization to the date of death from any cause. For each participant who is not known to have died as of the data-inclusion cut-off date for a particular analysis, overall survival duration was censored for that analysis at the date of last prior contact.
Time Frame Baseline to Date of Death Due to Any Cause (Up To 38 Months)
Hide Outcome Measure Data
Hide Analysis Population Description
Phase 2: All randomized participants (including the censored participants). Number of participants censored in "Olaratumab + Gemcitabine + Docetaxel (Olaratumab Pre-Treated) = 20," "Placebo + Gemcitabine + Docetaxel (Olaratumab Pre-Treated) =15."
Arm/Group Title Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab Pre-treated) Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab Pre-treated)
Hide Arm/Group Description:
This cohort included participants who received commercially available olaratumab prior to enrollment. Participants received intravenous infusions of olaratumab loading dose 20 mg/kg on days 1, 8 of cycle 1 followed by 15 mg/kg on days 1, 8 of all subsequent cycles in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.
This cohort included participants who received commercially available olaratumab prior to enrollment. Participants received intravenous infusions of placebo on days 1, 8 in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.
Overall Number of Participants Analyzed 46 43
Median (95% Confidence Interval)
Unit of Measure: Months
19.84 [1] 
(14.19 to NA)
17.31
(10.81 to 20.30)
[1]
There were not enough events to estimate the upper confidence limit.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab Pre-treated), Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab Pre-treated)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.148
Comments Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.667
Confidence Interval (2-Sided) 95%
0.385 to 1.158
Estimation Comments Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).
13.Secondary Outcome
Title Phase 2: Progression Free Survival (PFS)
Hide Description PFS was defined as the time from randomization to the first date of radiologic disease progression (as defined by Response Evaluation Criteria In Solid Tumors, Version 1.1 [RECIST v.1.1]) or death due to any cause. Progressive disease (PD) was defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. Participants who have neither progressed nor died were censored at the day of their last radiographic tumor assessment, if available, or date of randomization if no post-baseline radiographic assessment is available.
Time Frame Baseline to Objective Disease Progression or Death from Any Cause (Up To 38 Months)
Hide Outcome Measure Data
Hide Analysis Population Description
Phase 2: All randomized participants (including the censored participants). Number of participants censored in "Olaratumab + Gemcitabine + Docetaxel (Olaratumab-naive)=20" "Placebo + Gemcitabine + Docetaxel (Olaratumab-naive)=21," "Olaratumab + Gemcitabine + Docetaxel (Olaratumab pre-treated)=12," "Placebo + Gemcitabine + Docetaxel (Olaratumab pre-treated)=16."
Arm/Group Title Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab-naive) Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab-naive) Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab Pre-treated) Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab Pre-treated)
Hide Arm/Group Description:
This cohort included participants who never received olaratumab prior to enrollment. Participants received intravenous infusions of olaratumab loading dose 20 mg/kg on days 1, 8 of cycle 1 followed by 15 mg/kg on days 1, 8 of all subsequent cycles in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.
This cohort included participants who never received olaratumab prior to enrollment. Participants received intravenous infusions of placebo on days 1, 8 in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.
This cohort included participants who received commercially available olaratumab prior to enrollment. Participants received intravenous infusions of olaratumab loading dose 20 mg/kg on days 1, 8 of cycle 1 followed by 15 mg/kg on days 1, 8 of all subsequent cycles in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.
This cohort included participants who received commercially available olaratumab prior to enrollment. Participants received intravenous infusions of placebo on days 1, 8 in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.
Overall Number of Participants Analyzed 81 86 46 43
Median (95% Confidence Interval)
Unit of Measure: Months
7.62
(5.13 to 8.54)
4.37
(2.86 to 6.87)
5.45
(2.76 to 8.71)
4.17
(2.20 to 6.90)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab-naive), Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab-naive)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.055
Comments Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.692
Confidence Interval (2-Sided) 95%
0.476 to 1.007
Estimation Comments Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab Pre-treated), Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab Pre-treated)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.482
Comments Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.828
Confidence Interval (2-Sided) 95%
0.490 to 1.398
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Phase 2: Percentage of Participants With a Complete or Partial Response (Objective Response Rate [ORR])
Hide Description ORR is the best overall tumor response of complete response (CR) or partial response (PR) as classified by the investigator according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1). CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions.
Time Frame Baseline to Objective Disease Progression or Start of New Anti-Cancer Therapy (Up To 38 Months)
Hide Outcome Measure Data
Hide Analysis Population Description
Phase 2: All randomized participants.
Arm/Group Title Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab-naive) Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab-naive) Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab Pre-treated) Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab Pre-treated)
Hide Arm/Group Description:
This cohort included participants who never received olaratumab prior to enrollment. Participants received intravenous infusions of olaratumab loading dose 20 mg/kg on days 1, 8 of cycle 1 followed by 15 mg/kg on days 1, 8 of all subsequent cycles in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.
This cohort included participants who never received olaratumab prior to enrollment. Participants received intravenous infusions of placebo on days 1, 8 in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.
This cohort included participants who received commercially available olaratumab prior to enrollment. Participants received intravenous infusions of olaratumab loading dose 20 mg/kg on days 1, 8 of cycle 1 followed by 15 mg/kg on days 1, 8 of all subsequent cycles in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.
This cohort included participants who received commercially available olaratumab prior to enrollment. Participants received intravenous infusions of placebo on days 1, 8 in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.
Overall Number of Participants Analyzed 81 86 46 43
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
32.1
(22.2 to 43.4)
23.3
(14.8 to 33.6)
30.4
(17.7 to 45.8)
14
(5.3 to 27.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab-naive), Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab-naive)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1891
Comments Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).
Method Exact Mantel-Haenszel test
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.589
Confidence Interval (2-Sided) 95%
0.794 to 3.179
Estimation Comments Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab Pre-treated), Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab Pre-treated)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0642
Comments Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).
Method Exact Mantel-Haenszel test
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.668
Confidence Interval (2-Sided) 95%
0.923 to 7.710
Estimation Comments Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).
15.Secondary Outcome
Title Phase 2: Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR), and Stable Disease (SD)
Hide Description DCR is the percentage of participants with a best overall response of CR, PR or SD as defined by RECIST v1.1. CR is defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD) for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.
Time Frame Baseline to Measured Progressive Disease or Start of New Anti-Cancer Therapy (Up To 38 Months)
Hide Outcome Measure Data
Hide Analysis Population Description
Phase 2: All randomized participants.
Arm/Group Title Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab-naive) Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab-naive) Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab Pre-treated) Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab Pre-treated)
Hide Arm/Group Description:
This cohort included participants who never received olaratumab prior to enrollment. Participants received intravenous infusions of olaratumab loading dose 20 mg/kg on days 1, 8 of cycle 1 followed by 15 mg/kg on days 1, 8 of all subsequent cycles in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.
This cohort included participants who never received olaratumab prior to enrollment. Participants received intravenous infusions of placebo on days 1, 8 in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.
This cohort included participants who received commercially available olaratumab prior to enrollment. Participants received intravenous infusions of olaratumab loading dose 20 mg/kg on days 1, 8 of cycle 1 followed by 15 mg/kg on days 1, 8 of all subsequent cycles in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.
This cohort included participants who received commercially available olaratumab prior to enrollment. Participants received intravenous infusions of placebo on days 1, 8 in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.
Overall Number of Participants Analyzed 81 86 46 43
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
74.1
(63.1 to 83.2)
72.1
(61.4 to 81.2)
67.4
(52.0 to 80.5)
62.8
(46.7 to 77.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab-naive), Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab-naive)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7724
Comments Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).
Method Exact Mantel-Haenszel test
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.106
Confidence Interval (2-Sided) 95%
0.558 to 2.194
Estimation Comments Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab Pre-treated), Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab Pre-treated)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6508
Comments Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).
Method Exact Mantel-Haenszel test
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.222
Confidence Interval (2-Sided) 95%
0.513 to 2.911
Estimation Comments Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).
16.Secondary Outcome
Title Phase 2: Time to First Worsening of the Brief Pain Inventory Short Form Modified (mBPI-sf) "Worst Pain Score"
Hide Description The mBPI-sf is a 11-item instrument used as a multiple-item measure of cancer pain intensity ranging from 0 (no pain or does not interfere) and ranged through 10 (pain as bad as you can imagine or completely interferes). Time to first worsening of the mBPI-sf "worst pain score" (TWP) was defined as the time from the date of randomization to the first date of either a "worst pain" score increase of greater than or equal to (≥) 2 points from baseline or an analgesic drug class increase of ≥1 level. If the patient has not worsened by either of these criteria, TWP was censored for analysis on the last date the mBPI-sf was administered.
Time Frame Baseline to Follow-up (Up To 24 Months)
Hide Outcome Measure Data
Hide Analysis Population Description
Phase 2: All randomized participants who had baseline and at least one post-baseline assessment (including the censored participants). Number of participants censored in "Olaratumab + Gemcitabine + Docetaxel (Olaratumab-naive) = 30," "Placebo + Gemcitabine + Docetaxel (Olaratumab-naive)=23," "Olaratumab + Gemcitabine + Docetaxel (Olaratumab pre-treated)=17," "Placebo + Gemcitabine + Docetaxel (Olaratumab pre-treated)=8."
Arm/Group Title Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab-naive) Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab-naive) Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab Pre-treated) Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab Pre-treated)
Hide Arm/Group Description:
This cohort included participants who never received olaratumab prior to enrollment. Participants received intravenous infusions of olaratumab loading dose 20 mg/kg on days 1, 8 of cycle 1 followed by 15 mg/kg on days 1, 8 of all subsequent cycles in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.
This cohort included participants who never received olaratumab prior to enrollment. Participants received intravenous infusions of placebo on days 1, 8 in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.
This cohort included participants who received commercially available olaratumab prior to enrollment. Participants received intravenous infusions of olaratumab loading dose 20 mg/kg on days 1, 8 of cycle 1 followed by 15 mg/kg on days 1, 8 of all subsequent cycles in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.
This cohort included participants who received commercially available olaratumab prior to enrollment. Participants received intravenous infusions of placebo on days 1, 8 in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.
Overall Number of Participants Analyzed 68 71 41 34
Median (95% Confidence Interval)
Unit of Measure: Months
3.61
(2.66 to 8.57)
2.27
(1.41 to 6.54)
3.15
(1.41 to 7.62)
2.20
(0.76 to 3.02)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab-naive), Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab-naive)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.073
Comments Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.661
Confidence Interval (2-Sided) 95%
0.419 to 1.041
Estimation Comments Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab Pre-treated), Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab Pre-treated)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.225
Comments Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.703
Confidence Interval (2-Sided) 95%
0.395 to 1.253
Estimation Comments Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).
17.Secondary Outcome
Title Phase 2: Time to First Worsening of Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) - Symptom Scales.
Hide Description The EORTC QLQ-C30 is a self-reported general cancer instrument consisting of 30 items covered by 1 of 3 dimensions: global health status/quality of life (2 items), functional scales (15 total items addressing either physical, role, emotional, cognitive, or social functioning), symptom scales (13 total items addressing either fatigue, nausea/vomiting, pain, dyspnoea, insomnia, appetite loss, constipation, diarrhoea, or financial impact). Time to first worsening of Symptom Burden was defined as the time from randomization to the first observation of worsening on symptom scales (i.e.,) increase of at least 10 points from baseline. For symptom scales, a linear transformation was used to obtain total score ranging from 0 to 100, a high score represents a high level of symptomatology or problems.
Time Frame Baseline to Follow-up (Up to 33 months)
Hide Outcome Measure Data
Hide Analysis Population Description
Phase 2: All randomized participants who had baseline and at least one post-baseline assessment.
Arm/Group Title Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab-naive) Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab-naive) Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab Pre-treated) Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab Pre-treated)
Hide Arm/Group Description:
This cohort included participants who never received olaratumab prior to enrollment. Participants received intravenous infusions of olaratumab loading dose 20 mg/kg on days 1, 8 of cycle 1 followed by 15 mg/kg on days 1, 8 of all subsequent cycles in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.
This cohort included participants who never received olaratumab prior to enrollment. Participants received intravenous infusions of placebo on days 1, 8 in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.
This cohort included participants who received commercially available olaratumab prior to enrollment. Participants received intravenous infusions of olaratumab loading dose 20 mg/kg on days 1, 8 of cycle 1 followed by 15 mg/kg on days 1, 8 of all subsequent cycles in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.
This cohort included participants who received commercially available olaratumab prior to enrollment. Participants received intravenous infusions of placebo on days 1, 8 in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.
Overall Number of Participants Analyzed 75 80 45 41
Median (95% Confidence Interval)
Unit of Measure: Months
Fatigue Number Analyzed 75 participants 77 participants 44 participants 39 participants
0.95
(0.76 to 1.12)
0.95
(0.76 to 1.45)
0.85
(0.72 to 1.41)
0.76
(0.72 to 1.84)
Nausea and vomiting Number Analyzed 74 participants 78 participants 44 participants 41 participants
3.78 [1] 
(2.14 to NA)
2.46
(0.99 to 13.34)
3.98 [1] 
(1.41 to NA)
13.17 [1] 
(1.64 to NA)
Pain Number Analyzed 73 participants 77 participants 44 participants 35 participants
4.67
(2.33 to 9.53)
0.99
(0.79 to 2.76)
2.43
(1.41 to 8.77)
3.06
(0.76 to 5.55)
Dyspnoea Number Analyzed 74 participants 78 participants 43 participants 39 participants
2.14
(1.51 to 3.06)
2.14
(1.48 to 2.86)
2.33
(1.45 to 14.09)
2.79
(1.45 to 8.05)
Insomnia Number Analyzed 68 participants 74 participants 41 participants 38 participants
5.32
(2.33 to 7.72)
4.24
(1.48 to 16.82)
1.91
(1.41 to 6.47)
5.09 [1] 
(1.45 to NA)
Appetite loss Number Analyzed 73 participants 76 participants 45 participants 37 participants
1.12
(0.82 to 2.14)
2.56
(1.64 to 3.98)
1.41
(0.85 to 3.52)
1.97
(1.38 to 4.04)
Constipation Number Analyzed 73 participants 77 participants 44 participants 40 participants
3.25
(2.14 to 5.98)
2.86 [1] 
(1.48 to NA)
4.63
(1.91 to 12.91)
3.81 [1] 
(1.97 to NA)
Diarrhoea Number Analyzed 75 participants 80 participants 44 participants 41 participants
1.41
(0.99 to 3.68)
1.81
(1.41 to 4.24)
3.55
(1.41 to 6.05)
3.52 [1] 
(1.97 to NA)
Financial difficulties Number Analyzed 67 participants 71 participants 43 participants 35 participants
NA [2] 
(5.32 to NA)
7.66 [1] 
(3.29 to NA)
7.29
(2.33 to 7.85)
NA [1] 
(3.94 to NA)
[1]
There were not enough events to estimate the upper confidence limit.
[2]
There were not enough events to estimate the median, upper confidence limit.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab-naive), Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab-naive)
Comments Fatigue
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.332
Comments Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.213
Confidence Interval (2-Sided) 95%
0.834 to 1.764
Estimation Comments Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab-naive), Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab-naive)
Comments Nausea and vomiting
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.389
Comments Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.813
Confidence Interval (2-Sided) 95%
0.514 to 1.287
Estimation Comments Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab-naive), Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab-naive)
Comments Pain
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.020
Comments Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.598
Confidence Interval (2-Sided) 95%
0.386 to 0.926
Estimation Comments Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab-naive), Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab-naive)
Comments Dyspnoea
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.821
Comments Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.947
Confidence Interval (2-Sided) 95%
0.622 to 1.442
Estimation Comments Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab-naive), Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab-naive)
Comments Insomnia
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.812
Comments Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.931
Confidence Interval (2-Sided) 95%
0.574 to 1.509
Estimation Comments Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab-naive), Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab-naive)
Comments Appetite loss
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.162
Comments Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.355
Confidence Interval (2-Sided) 95%
0.893 to 2.055
Estimation Comments Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab-naive), Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab-naive)
Comments Constipation
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.619
Comments Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.881
Confidence Interval (2-Sided) 95%
0.550 to 1.413
Estimation Comments Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab-naive), Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab-naive)
Comments Diarrhoea
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.597
Comments Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.134
Confidence Interval (2-Sided) 95%
0.746 to 1.724
Estimation Comments Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab-naive), Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab-naive)
Comments Financial difficulties
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.380
Comments Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.766
Confidence Interval (2-Sided) 95%
0.425 to 1.381
Estimation Comments Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab Pre-treated), Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab Pre-treated)
Comments Fatigue
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.877
Comments Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.046
Confidence Interval (2-Sided) 95%
0.635 to 1.723
Estimation Comments Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab Pre-treated), Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab Pre-treated)
Comments Nausea and vomiting
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.791
Comments Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.102
Confidence Interval (2-Sided) 95%
0.568 to 2.139
Estimation Comments Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab Pre-treated), Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab Pre-treated)
Comments Pain
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.487
Comments Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.810
Confidence Interval (2-Sided) 95%
0.454 to 1.443
Estimation Comments Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).
Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab Pre-treated), Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab Pre-treated)
Comments Dyspnoea
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.976
Comments Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.014
Confidence Interval (2-Sided) 95%
0.556 to 1.850
Estimation Comments Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).
Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab Pre-treated), Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab Pre-treated)
Comments Insomnia
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.111
Comments Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.694
Confidence Interval (2-Sided) 95%
0.882 to 3.250
Estimation Comments Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).
Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab Pre-treated), Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab Pre-treated)
Comments Appetite loss
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.760
Comments Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.108
Confidence Interval (2-Sided) 95%
0.620 to 1.979
Estimation Comments Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).
Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab Pre-treated), Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab Pre-treated)
Comments Constipation
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.747
Comments Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.119
Confidence Interval (2-Sided) 95%
0.586 to 2.135
Estimation Comments Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).
Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab Pre-treated), Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab Pre-treated)
Comments Diarrhoea
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.330
Comments Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.367
Confidence Interval (2-Sided) 95%
0.726 to 2.576
Estimation Comments Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).
Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab Pre-treated), Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab Pre-treated)
Comments Financial difficulties
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.411
Comments Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.373
Confidence Interval (2-Sided) 95%
0.636 to 2.965
Estimation Comments Stratified by number of prior systemic therapies for locally advanced or metastatic disease (0 vs ≥1), histological tumor type (leiomyosarcoma vs non-leiomyosarcoma), and ECOG PS (0 vs1).
18.Secondary Outcome
Title Phase 2: Health Status on the EuroQol 5-Dimension 5 Level (EQ-5D-5L)
Hide Description The EQ-5D-5L is a standardized instrument for use as a measure of self-reported health status. Five dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) of health status are each assessed with 5 response options (1=no problem, 2=slight, 3=moderate, 4=severe, and 5=extreme problem) and scored as a composite index which were anchored on a scale of 0 to 1 with a higher score representing better health status. Additionally, current health status was assessed on a visual analogue scale (VAS) ranging from 0 to 100 with a higher score representing better health status.
Time Frame Cycle 1 (Day 1), Follow-up (Up to 38 Months)
Hide Outcome Measure Data
Hide Analysis Population Description
Phase 2: All randomized participants who completed EQ-5D-5L.
Arm/Group Title Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab-naive) Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab-naive) Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab Pre-treated) Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab Pre-treated)
Hide Arm/Group Description:
This cohort included participants who never received olaratumab prior to enrollment. Participants received intravenous infusions of olaratumab loading dose 20 mg/kg on days 1, 8 of cycle 1 followed by 15 mg/kg on days 1, 8 of all subsequent cycles in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.
This cohort included participants who never received olaratumab prior to enrollment. Participants received intravenous infusions of placebo on days 1, 8 in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.
This cohort included participants who received commercially available olaratumab prior to enrollment. Participants received intravenous infusions of olaratumab loading dose 20 mg/kg on days 1, 8 of cycle 1 followed by 15 mg/kg on days 1, 8 of all subsequent cycles in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.
This cohort included participants who received commercially available olaratumab prior to enrollment. Participants received intravenous infusions of placebo on days 1, 8 in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.
Overall Number of Participants Analyzed 71 75 42 35
Mean (Standard Deviation)
Unit of Measure: score on a scale
EQ-5D-5L - Index Value [Cycle 1 (Day 1)] Number Analyzed 71 participants 74 participants 39 participants 35 participants
0.80  (0.17) 0.81  (0.17) 0.83  (0.15) 0.83  (0.22)
EQ-5D-5L - VAS Score [Cycle 1 (Day 1)] Number Analyzed 71 participants 75 participants 42 participants 35 participants
73.5  (18.9) 72.7  (18.1) 76.2  (19.6) 70.3  (23.8)
EQ-5D-5L - Index Value [Follow-up (Up to 38 Months)] Number Analyzed 42 participants 50 participants 26 participants 25 participants
0.74  (0.21) 0.71  (0.26) 0.80  (0.20) 0.76  (0.24)
EQ-5D-5L - VAS Score [Follow-up (Up to 38 Months)] Number Analyzed 42 participants 50 participants 26 participants 25 participants
68.7  (16.5) 63.0  (21.6) 74.8  (21.8) 70.8  (24.2)
19.Secondary Outcome
Title Phase 2: Number of Participants With Treatment Emergent Anti-Olaratumab Antibodies
Hide Description Number of Participants with Treatment Emergent Anti-Olaratumab Antibodies
Time Frame Baseline through Follow-Up (Up to 38 Months)
Hide Outcome Measure Data
Hide Analysis Population Description
Phase 2: All randomized participants who received at least one dose of Olaratumab and had evaluable immunogenicity data.
Arm/Group Title Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab-naive) Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab Pre-treated)
Hide Arm/Group Description:
This cohort included participants who never received olaratumab prior to enrollment. Participants received intravenous infusions of olaratumab loading dose 20 mg/kg on days 1, 8 of cycle 1 followed by 15 mg/kg on days 1, 8 of all subsequent cycles in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.
This cohort included participants who received commercially available olaratumab prior to enrollment. Participants received intravenous infusions of olaratumab loading dose 20 mg/kg on days 1, 8 of cycle 1 followed by 15 mg/kg on days 1, 8 of all subsequent cycles in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.
Overall Number of Participants Analyzed 77 43
Measure Type: Count of Participants
Unit of Measure: Participants
0 0
Time Frame Baseline to Follow-up (Up To 38 Months)
Adverse Event Reporting Description Phase 1b/2: All participants who received at least one dose of study drug. Gender specific events only occurring in male or female participants have had the number of participants At Risk adjusted accordingly.
 
Arm/Group Title Phase 1b: Cohort 1 - 15 mg/kg Olaratumab + Gemcitabine + Docetaxel Phase 1b: Cohort 2 - 20 mg/kg Olaratumab + Gemcitabine + Docetaxel Phase 1b: Cohort 2 Expansion - 20 mg/kg Olaratumab + Gemcitabine + Docetaxel Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab-naive) Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab Pre-treated) Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab-naive) Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab Pre-treated)
Hide Arm/Group Description Participants received intravenous infusions of olaratumab 15 milligrams per kilogram (mg/kg) on days 1, 8 plus gemcitabine 900 milligrams per meter square (mg/m^2) on days 1, 8 plus docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met. Participants received intravenous infusions of olaratumab 20 mg/kg on days 1, 8 in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met. Following a protocol amendment, additional participants were enrolled into this group to confirm the safety of the 20 mg/kg dose level prior to opening the Phase 2. Participants received intravenous infusions of olaratumab 20 milligrams per kilogram (mg/kg) on days 1, 8 plus gemcitabine 900 milligrams per meter square (mg/m^2) on days 1, 8 plus docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met. This cohort included participants who never received olaratumab prior to enrollment. Participants received intravenous infusions of olaratumab loading dose 20 mg/kg on days 1, 8 of cycle 1 followed by 15 mg/kg on days 1, 8 of all subsequent cycles in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met. This cohort included participants who received commercially available olaratumab prior to enrollment. Participants received intravenous infusions of olaratumab loading dose 20 mg/kg on days 1, 8 of cycle 1 followed by 15 mg/kg on days 1, 8 of all subsequent cycles in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met. This cohort included participants who never received olaratumab prior to enrollment. Participants received intravenous infusions of placebo on days 1, 8 in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met. This cohort included participants who received commercially available olaratumab prior to enrollment. Participants received intravenous infusions of placebo on days 1, 8 in combination with gemcitabine 900 mg/m^2 on days 1, 8 and docetaxel 75 mg/m^2 on day 8 of a 21-day cycle until disease progression, unacceptable toxicity, death, or other discontinuation criteria were met.
All-Cause Mortality
Phase 1b: Cohort 1 - 15 mg/kg Olaratumab + Gemcitabine + Docetaxel Phase 1b: Cohort 2 - 20 mg/kg Olaratumab + Gemcitabine + Docetaxel Phase 1b: Cohort 2 Expansion - 20 mg/kg Olaratumab + Gemcitabine + Docetaxel Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab-naive) Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab Pre-treated) Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab-naive) Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab Pre-treated)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   5/21 (23.81%)      5/18 (27.78%)      0/15 (0.00%)      51/81 (62.96%)      26/45 (57.78%)      58/86 (67.44%)      28/43 (65.12%)    
Hide Serious Adverse Events
Phase 1b: Cohort 1 - 15 mg/kg Olaratumab + Gemcitabine + Docetaxel Phase 1b: Cohort 2 - 20 mg/kg Olaratumab + Gemcitabine + Docetaxel Phase 1b: Cohort 2 Expansion - 20 mg/kg Olaratumab + Gemcitabine + Docetaxel Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab-naive) Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab Pre-treated) Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab-naive) Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab Pre-treated)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/21 (28.57%)      9/18 (50.00%)      9/15 (60.00%)      44/81 (54.32%)      21/45 (46.67%)      38/86 (44.19%)      23/43 (53.49%)    
Blood and lymphatic system disorders               
Anaemia  1  0/21 (0.00%)  0 1/18 (5.56%)  1 0/15 (0.00%)  0 4/81 (4.94%)  7 2/45 (4.44%)  2 4/86 (4.65%)  5 0/43 (0.00%)  0
Bandaemia  1  0/21 (0.00%)  0 1/18 (5.56%)  1 0/15 (0.00%)  0 0/81 (0.00%)  0 0/45 (0.00%)  0 0/86 (0.00%)  0 0/43 (0.00%)  0
Febrile neutropenia  1  0/21 (0.00%)  0 1/18 (5.56%)  1 1/15 (6.67%)  1 6/81 (7.41%)  6 1/45 (2.22%)  1 3/86 (3.49%)  3 1/43 (2.33%)  1
Haemolytic uraemic syndrome  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 0/81 (0.00%)  0 0/45 (0.00%)  0 1/86 (1.16%)  2 0/43 (0.00%)  0
Hypochromic anaemia  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 0/81 (0.00%)  0 0/45 (0.00%)  0 0/86 (0.00%)  0 1/43 (2.33%)  1
Neutropenia  1  0/21 (0.00%)  0 1/18 (5.56%)  1 0/15 (0.00%)  0 1/81 (1.23%)  1 2/45 (4.44%)  2 2/86 (2.33%)  2 1/43 (2.33%)  1
Neutrophilia  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 0/81 (0.00%)  0 0/45 (0.00%)  0 0/86 (0.00%)  0 1/43 (2.33%)  1
Normocytic anaemia  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 1/81 (1.23%)  1 0/45 (0.00%)  0 0/86 (0.00%)  0 0/43 (0.00%)  0
Pancytopenia  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 1/81 (1.23%)  1 0/45 (0.00%)  0 2/86 (2.33%)  2 0/43 (0.00%)  0
Thrombocytopenia  1  0/21 (0.00%)  0 0/18 (0.00%)  0 1/15 (6.67%)  1 2/81 (2.47%)  3 3/45 (6.67%)  5 3/86 (3.49%)  5 2/43 (4.65%)  2
Thrombotic microangiopathy  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 1/81 (1.23%)  1 0/45 (0.00%)  0 0/86 (0.00%)  0 0/43 (0.00%)  0
Cardiac disorders               
Atrial fibrillation  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 0/81 (0.00%)  0 0/45 (0.00%)  0 1/86 (1.16%)  1 1/43 (2.33%)  1
Atrial tachycardia  1  0/21 (0.00%)  0 0/18 (0.00%)  0 1/15 (6.67%)  1 0/81 (0.00%)  0 0/45 (0.00%)  0 0/86 (0.00%)  0 0/43 (0.00%)  0
Cardiac failure  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 1/81 (1.23%)  1 0/45 (0.00%)  0 1/86 (1.16%)  1 0/43 (0.00%)  0
Myocardial infarction  1  0/21 (0.00%)  0 1/18 (5.56%)  1 0/15 (0.00%)  0 0/81 (0.00%)  0 0/45 (0.00%)  0 1/86 (1.16%)  1 0/43 (0.00%)  0
Pericardial effusion  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 0/81 (0.00%)  0 0/45 (0.00%)  0 1/86 (1.16%)  1 0/43 (0.00%)  0
Supraventricular tachycardia  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 1/81 (1.23%)  1 0/45 (0.00%)  0 0/86 (0.00%)  0 0/43 (0.00%)  0
Ear and labyrinth disorders               
Hypoacusis  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 0/81 (0.00%)  0 0/45 (0.00%)  0 1/86 (1.16%)  1 0/43 (0.00%)  0
Gastrointestinal disorders               
Abdominal pain  1  0/21 (0.00%)  0 1/18 (5.56%)  1 0/15 (0.00%)  0 1/81 (1.23%)  1 0/45 (0.00%)  0 0/86 (0.00%)  0 1/43 (2.33%)  1
Constipation  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 0/81 (0.00%)  0 1/45 (2.22%)  1 0/86 (0.00%)  0 1/43 (2.33%)  1
Diarrhoea  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 2/81 (2.47%)  2 1/45 (2.22%)  1 1/86 (1.16%)  1 0/43 (0.00%)  0
Enterocolitis  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 1/81 (1.23%)  1 0/45 (0.00%)  0 0/86 (0.00%)  0 0/43 (0.00%)  0
Gastritis  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 0/81 (0.00%)  0 0/45 (0.00%)  0 1/86 (1.16%)  1 0/43 (0.00%)  0
Haemorrhoidal haemorrhage  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 0/81 (0.00%)  0 1/45 (2.22%)  1 0/86 (0.00%)  0 0/43 (0.00%)  0
Nausea  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 2/81 (2.47%)  3 0/45 (0.00%)  0 0/86 (0.00%)  0 0/43 (0.00%)  0
Oesophageal ulcer  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 0/81 (0.00%)  0 0/45 (0.00%)  0 0/86 (0.00%)  0 1/43 (2.33%)  1
Rectal haemorrhage  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 0/81 (0.00%)  0 1/45 (2.22%)  1 0/86 (0.00%)  0 0/43 (0.00%)  0
Small intestinal obstruction  1  0/21 (0.00%)  0 0/18 (0.00%)  0 1/15 (6.67%)  1 0/81 (0.00%)  0 1/45 (2.22%)  1 1/86 (1.16%)  1 0/43 (0.00%)  0
Stomatitis  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 0/81 (0.00%)  0 1/45 (2.22%)  3 0/86 (0.00%)  0 0/43 (0.00%)  0
Vomiting  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 2/81 (2.47%)  2 0/45 (0.00%)  0 1/86 (1.16%)  1 0/43 (0.00%)  0
General disorders               
Chest pain  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 1/81 (1.23%)  1 0/45 (0.00%)  0 0/86 (0.00%)  0 0/43 (0.00%)  0
Fatigue  1  0/21 (0.00%)  0 0/18 (0.00%)  0 1/15 (6.67%)  1 3/81 (3.70%)  3 1/45 (2.22%)  1 0/86 (0.00%)  0 0/43 (0.00%)  0
Influenza like illness  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 0/81 (0.00%)  0 1/45 (2.22%)  1 1/86 (1.16%)  1 0/43 (0.00%)  0
Mucosal inflammation  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 0/81 (0.00%)  0 0/45 (0.00%)  0 1/86 (1.16%)  1 0/43 (0.00%)  0
Non-cardiac chest pain  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 1/81 (1.23%)  1 0/45 (0.00%)  0 0/86 (0.00%)  0 1/43 (2.33%)  1
Oedema  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 0/81 (0.00%)  0 0/45 (0.00%)  0 1/86 (1.16%)  1 1/43 (2.33%)  1
Oedema peripheral  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 2/81 (2.47%)  2 2/45 (4.44%)  2 0/86 (0.00%)  0 0/43 (0.00%)  0
Peripheral swelling  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 0/81 (0.00%)  0 0/45 (0.00%)  0 0/86 (0.00%)  0 1/43 (2.33%)  1
Pyrexia  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 7/81 (8.64%)  10 2/45 (4.44%)  2 7/86 (8.14%)  8 6/43 (13.95%)  6
Sudden death  1  0/21 (0.00%)  0 1/18 (5.56%)  1 0/15 (0.00%)  0 0/81 (0.00%)  0 0/45 (0.00%)  0 0/86 (0.00%)  0 0/43 (0.00%)  0
Hepatobiliary disorders               
Hepatic failure  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 0/81 (0.00%)  0 1/45 (2.22%)  1 0/86 (0.00%)  0 0/43 (0.00%)  0
Jaundice cholestatic  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 0/81 (0.00%)  0 0/45 (0.00%)  0 0/86 (0.00%)  0 1/43 (2.33%)  1
Immune system disorders               
Anaphylactic reaction  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 1/81 (1.23%)  1 0/45 (0.00%)  0 0/86 (0.00%)  0 0/43 (0.00%)  0
Anaphylactic shock  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 0/81 (0.00%)  0 0/45 (0.00%)  0 1/86 (1.16%)  1 0/43 (0.00%)  0
Infections and infestations               
Anorectal infection  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 0/81 (0.00%)  0 1/45 (2.22%)  1 0/86 (0.00%)  0 0/43 (0.00%)  0
Appendicitis  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 1/81 (1.23%)  1 0/45 (0.00%)  0 0/86 (0.00%)  0 0/43 (0.00%)  0
Arthritis infective  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 0/81 (0.00%)  0 0/45 (0.00%)  0 1/86 (1.16%)  1 0/43 (0.00%)  0
Bacteraemia  1  0/21 (0.00%)  0 1/18 (5.56%)  1 0/15 (0.00%)  0 0/81 (0.00%)  0 0/45 (0.00%)  0 1/86 (1.16%)  1 0/43 (0.00%)  0
Bronchitis  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 0/81 (0.00%)  0 1/45 (2.22%)  1 0/86 (0.00%)  0 1/43 (2.33%)  1
Campylobacter infection  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 0/81 (0.00%)  0 1/45 (2.22%)  1 0/86 (0.00%)  0 0/43 (0.00%)  0
Cellulitis  1  1/21 (4.76%)  4 1/18 (5.56%)  1 1/15 (6.67%)  1 2/81 (2.47%)  2 1/45 (2.22%)  1 1/86 (1.16%)  1 0/43 (0.00%)  0
Clostridium difficile colitis  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 1/81 (1.23%)  1 0/45 (0.00%)  0 0/86 (0.00%)  0 0/43 (0.00%)  0
Cystitis  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 0/81 (0.00%)  0 0/45 (0.00%)  0 2/86 (2.33%)  2 0/43 (0.00%)  0
Device related infection  1  0/21 (0.00%)  0 1/18 (5.56%)  1 0/15 (0.00%)  0 1/81 (1.23%)  1 0/45 (0.00%)  0 1/86 (1.16%)  1 0/43 (0.00%)  0
Diverticulitis  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 2/81 (2.47%)  2 1/45 (2.22%)  1 0/86 (0.00%)  0 0/43 (0.00%)  0
Erysipelas  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 1/81 (1.23%)  1 0/45 (0.00%)  0 0/86 (0.00%)  0 0/43 (0.00%)  0
Gastrointestinal infection  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 0/81 (0.00%)  0 1/45 (2.22%)  1 0/86 (0.00%)  0 0/43 (0.00%)  0
Influenza  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 0/81 (0.00%)  0 1/45 (2.22%)  1 1/86 (1.16%)  1 0/43 (0.00%)  0
Lower respiratory tract infection  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 2/81 (2.47%)  2 1/45 (2.22%)  1 1/86 (1.16%)  1 0/43 (0.00%)  0
Neutropenic sepsis  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 0/81 (0.00%)  0 0/45 (0.00%)  0 1/86 (1.16%)  1 0/43 (0.00%)  0
Pneumonia  1  2/21 (9.52%)  3 0/18 (0.00%)  0 0/15 (0.00%)  0 5/81 (6.17%)  5 3/45 (6.67%)  3 6/86 (6.98%)  6 5/43 (11.63%)  5
Pneumonia bacterial  1  1/21 (4.76%)  1 0/18 (0.00%)  0 0/15 (0.00%)  0 0/81 (0.00%)  0 0/45 (0.00%)  0 1/86 (1.16%)  1 0/43 (0.00%)  0
Pneumonia viral  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 0/81 (0.00%)  0 1/45 (2.22%)  1 0/86 (0.00%)  0 0/43 (0.00%)  0
Rectal abscess  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 0/81 (0.00%)  0 1/45 (2.22%)  1 0/86 (0.00%)  0 0/43 (0.00%)  0
Respiratory tract infection  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 1/81 (1.23%)  1 0/45 (0.00%)  0 1/86 (1.16%)  1 0/43 (0.00%)  0
Sepsis  1  0/21 (0.00%)  0 1/18 (5.56%)  1 0/15 (0.00%)  0 2/81 (2.47%)  2 0/45 (0.00%)  0 1/86 (1.16%)  1 2/43 (4.65%)  2
Septic shock  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 0/81 (0.00%)  0 0/45 (0.00%)  0 0/86 (0.00%)  0 1/43 (2.33%)  1
Skin infection  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 1/81 (1.23%)  1 0/45 (0.00%)  0 0/86 (0.00%)  0 1/43 (2.33%)  1
Staphylococcal bacteraemia  1  0/21 (0.00%)  0 0/18 (0.00%)  0 1/15 (6.67%)  1 0/81 (0.00%)  0 0/45 (0.00%)  0 0/86 (0.00%)  0 0/43 (0.00%)  0
Urinary tract infection  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 4/81 (4.94%)  4 0/45 (0.00%)  0 1/86 (1.16%)  1 0/43 (0.00%)  0
Viral infection  1  0/21 (0.00%)  0 1/18 (5.56%)  1 0/15 (0.00%)  0 0/81 (0.00%)  0 0/45 (0.00%)  0 0/86 (0.00%)  0 0/43 (0.00%)  0
Injury, poisoning and procedural complications               
Arterial bypass occlusion  1  1/21 (4.76%)  5 0/18 (0.00%)  0 0/15 (0.00%)  0 0/81 (0.00%)  0 0/45 (0.00%)  0 0/86 (0.00%)  0 0/43 (0.00%)  0
Fall  1  0/21 (0.00%)  0 0/18 (0.00%)  0 1/15 (6.67%)  1 0/81 (0.00%)  0 1/45 (2.22%)  1 1/86 (1.16%)  1 0/43 (0.00%)  0
Femoral neck fracture  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 0/81 (0.00%)  0 1/45 (2.22%)  1 0/86 (0.00%)  0 0/43 (0.00%)  0
Femur fracture  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 0/81 (0.00%)  0 1/45 (2.22%)  1 0/86 (0.00%)  0 0/43 (0.00%)  0
Hip fracture  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 0/81 (0.00%)  0 1/45 (2.22%)  1 0/86 (0.00%)  0 1/43 (2.33%)  1
Infusion related reaction  1  1/21 (4.76%)  1 0/18 (0.00%)  0 0/15 (0.00%)  0 1/81 (1.23%)  1 0/45 (0.00%)  0 0/86 (0.00%)  0 0/43 (0.00%)  0
Skull fracture  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 0/81 (0.00%)  0 0/45 (0.00%)  0 1/86 (1.16%)  1 0/43 (0.00%)  0
Investigations               
Alanine aminotransferase increased  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 1/81 (1.23%)  1 0/45 (0.00%)  0 0/86 (0.00%)  0 0/43 (0.00%)  0
International normalised ratio increased  1  0/21 (0.00%)  0 0/18 (0.00%)  0 1/15 (6.67%)  1 0/81 (0.00%)  0 0/45 (0.00%)  0 0/86 (0.00%)  0 0/43 (0.00%)  0
Neutrophil count decreased  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 1/81 (1.23%)  1 1/45 (2.22%)  1 1/86 (1.16%)  1 0/43 (0.00%)  0
Platelet count decreased  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 2/81 (2.47%)  2 1/45 (2.22%)  2 2/86 (2.33%)  2 1/43 (2.33%)  1
Troponin increased  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 0/81 (0.00%)  0 0/45 (0.00%)  0 0/86 (0.00%)  0 1/43 (2.33%)  1
White blood cell count decreased  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 0/81 (0.00%)  0 1/45 (2.22%)  1 0/86 (0.00%)  0 0/43 (0.00%)  0
Metabolism and nutrition disorders               
Dehydration  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 2/81 (2.47%)  2 0/45 (0.00%)  0 1/86 (1.16%)  1 0/43 (0.00%)  0
Hypokalaemia  1  0/21 (0.00%)  0 1/18 (5.56%)  1 0/15 (0.00%)  0 0/81 (0.00%)  0 0/45 (0.00%)  0 1/86 (1.16%)  1 0/43 (0.00%)  0
Musculoskeletal and connective tissue disorders               
Arthralgia  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 0/81 (0.00%)  0 0/45 (0.00%)  0 1/86 (1.16%)  1 0/43 (0.00%)  0
Arthritis  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 0/81 (0.00%)  0 0/45 (0.00%)  0 1/86 (1.16%)  1 0/43 (0.00%)  0
Back pain  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 1/81 (1.23%)  1 0/45 (0.00%)  0 0/86 (0.00%)  0 1/43 (2.33%)  1
Muscular weakness  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 0/81 (0.00%)  0 0/45 (0.00%)  0 1/86 (1.16%)  1 0/43 (0.00%)  0
Myalgia  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 0/81 (0.00%)  0 1/45 (2.22%)  1 0/86 (0.00%)  0 0/43 (0.00%)  0
Myositis  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 0/81 (0.00%)  0 1/45 (2.22%)  1 0/86 (0.00%)  0 0/43 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)               
Tumour haemorrhage  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 0/81 (0.00%)  0 0/45 (0.00%)  0 1/86 (1.16%)  2 0/43 (0.00%)  0
Nervous system disorders               
Dizziness  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 0/81 (0.00%)  0 0/45 (0.00%)  0 1/86 (1.16%)  1 0/43 (0.00%)  0
Epilepsy  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 0/81 (0.00%)  0 0/45 (0.00%)  0 1/86 (1.16%)  1 0/43 (0.00%)  0
Facial paralysis  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 0/81 (0.00%)  0 0/45 (0.00%)  0 1/86 (1.16%)  1 0/43 (0.00%)  0
Headache  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 0/81 (0.00%)  0 0/45 (0.00%)  0 1/86 (1.16%)  1 0/43 (0.00%)  0
Nervous system disorder  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 0/81 (0.00%)  0 1/45 (2.22%)  1 0/86 (0.00%)  0 0/43 (0.00%)  0
Polyneuropathy  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 0/81 (0.00%)  0 0/45 (0.00%)  0 1/86 (1.16%)  1 0/43 (0.00%)  0
Seizure  1  1/21 (4.76%)  1 0/18 (0.00%)  0 0/15 (0.00%)  0 0/81 (0.00%)  0 0/45 (0.00%)  0 0/86 (0.00%)  0 0/43 (0.00%)  0
Spinal cord compression  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 1/81 (1.23%)  1 0/45 (0.00%)  0 0/86 (0.00%)  0 0/43 (0.00%)  0
Syncope  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 0/81 (0.00%)  0 1/45 (2.22%)  1 0/86 (0.00%)  0 0/43 (0.00%)  0
Psychiatric disorders               
Confusional state  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 1/81 (1.23%)  1 0/45 (0.00%)  0 0/86 (0.00%)  0 0/43 (0.00%)  0
Renal and urinary disorders               
Acute kidney injury  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 0/81 (0.00%)  0 1/45 (2.22%)  1 2/86 (2.33%)  2 0/43 (0.00%)  0
Renal failure  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 2/81 (2.47%)  2 0/45 (0.00%)  0 0/86 (0.00%)  0 0/43 (0.00%)  0
Urinary retention  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 0/81 (0.00%)  0 1/45 (2.22%)  1 0/86 (0.00%)  0 0/43 (0.00%)  0
Respiratory, thoracic and mediastinal disorders               
Cough  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 1/81 (1.23%)  1 0/45 (0.00%)  0 1/86 (1.16%)  1 0/43 (0.00%)  0
Dyspnoea  1  0/21 (0.00%)  0 1/18 (5.56%)  1 0/15 (0.00%)  0 3/81 (3.70%)  4 2/45 (4.44%)  2 4/86 (4.65%)  4 1/43 (2.33%)  1
Epistaxis  1  0/21 (0.00%)  0 0/18 (0.00%)  0 1/15 (6.67%)  1 0/81 (0.00%)  0 0/45 (0.00%)  0 2/86 (2.33%)  2 1/43 (2.33%)  1
Hypoxia  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 0/81 (0.00%)  0 0/45 (0.00%)  0 1/86 (1.16%)  1 0/43 (0.00%)  0
Interstitial lung disease  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 1/81 (1.23%)  1 0/45 (0.00%)  0 0/86 (0.00%)  0 0/43 (0.00%)  0
Pneumonitis  1  0/21 (0.00%)  0 0/18 (0.00%)  0 1/15 (6.67%)  1 1/81 (1.23%)  1 1/45 (2.22%)  1 2/86 (2.33%)  2 4/43 (9.30%)  4
Pneumothorax  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 1/81 (1.23%)  3 0/45 (0.00%)  0 0/86 (0.00%)  0 1/43 (2.33%)  1
Pulmonary embolism  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 0/81 (0.00%)  0 0/45 (0.00%)  0 1/86 (1.16%)  1 1/43 (2.33%)  1
Pulmonary haemorrhage  1  0/21 (0.00%)  0 0/18 (0.00%)  0 1/15 (6.67%)  1 0/81 (0.00%)  0 0/45 (0.00%)  0 0/86 (0.00%)  0 0/43 (0.00%)  0
Pulmonary oedema  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 1/81 (1.23%)  1 0/45 (0.00%)  0 0/86 (0.00%)  0 0/43 (0.00%)  0
Respiratory failure  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 0/81 (0.00%)  0 0/45 (0.00%)  0 0/86 (0.00%)  0 2/43 (4.65%)  2
Skin and subcutaneous tissue disorders               
Eczema  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 0/81 (0.00%)  0 0/45 (0.00%)  0 1/86 (1.16%)  1 0/43 (0.00%)  0
Petechiae  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 1/81 (1.23%)  1 0/45 (0.00%)  0 0/86 (0.00%)  0 0/43 (0.00%)  0
Vascular disorders               
Capillary leak syndrome  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 0/81 (0.00%)  0 0/45 (0.00%)  0 1/86 (1.16%)  1 0/43 (0.00%)  0
Deep vein thrombosis  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 1/81 (1.23%)  1 2/45 (4.44%)  3 1/86 (1.16%)  1 0/43 (0.00%)  0
Embolism  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 0/81 (0.00%)  0 1/45 (2.22%)  1 1/86 (1.16%)  1 0/43 (0.00%)  0
Haematoma  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 0/81 (0.00%)  0 0/45 (0.00%)  0 1/86 (1.16%)  1 0/43 (0.00%)  0
Haemorrhage  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 1/81 (1.23%)  1 0/45 (0.00%)  0 0/86 (0.00%)  0 0/43 (0.00%)  0
Hypotension  1  1/21 (4.76%)  1 0/18 (0.00%)  0 0/15 (0.00%)  0 1/81 (1.23%)  1 0/45 (0.00%)  0 0/86 (0.00%)  0 0/43 (0.00%)  0
Peripheral artery stenosis  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 0/81 (0.00%)  0 0/45 (0.00%)  0 1/86 (1.16%)  1 0/43 (0.00%)  0
1
Term from vocabulary, MedDRA 21.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Phase 1b: Cohort 1 - 15 mg/kg Olaratumab + Gemcitabine + Docetaxel Phase 1b: Cohort 2 - 20 mg/kg Olaratumab + Gemcitabine + Docetaxel Phase 1b: Cohort 2 Expansion - 20 mg/kg Olaratumab + Gemcitabine + Docetaxel Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab-naive) Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab Pre-treated) Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab-naive) Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab Pre-treated)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   21/21 (100.00%)      18/18 (100.00%)      15/15 (100.00%)      78/81 (96.30%)      45/45 (100.00%)      81/86 (94.19%)      42/43 (97.67%)    
Blood and lymphatic system disorders               
Anaemia  1  13/21 (61.90%)  42 12/18 (66.67%)  54 9/15 (60.00%)  24 43/81 (53.09%)  168 33/45 (73.33%)  145 47/86 (54.65%)  147 20/43 (46.51%)  57
Leukopenia  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 7/81 (8.64%)  13 1/45 (2.22%)  4 3/86 (3.49%)  6 1/43 (2.33%)  4
Neutropenia  1  3/21 (14.29%)  4 3/18 (16.67%)  4 2/15 (13.33%)  5 20/81 (24.69%)  55 6/45 (13.33%)  6 24/86 (27.91%)  43 4/43 (9.30%)  10
Neutrophilia  1  0/21 (0.00%)  0 0/18 (0.00%)  0 1/15 (6.67%)  1 0/81 (0.00%)  0 0/45 (0.00%)  0 0/86 (0.00%)  0 0/43 (0.00%)  0
Thrombocytopenia  1  2/21 (9.52%)  8 3/18 (16.67%)  3 4/15 (26.67%)  12 10/81 (12.35%)  21 9/45 (20.00%)  18 13/86 (15.12%)  21 6/43 (13.95%)  12
Cardiac disorders               
Atrial fibrillation  1  0/21 (0.00%)  0 0/18 (0.00%)  0 1/15 (6.67%)  1 0/81 (0.00%)  0 0/45 (0.00%)  0 1/86 (1.16%)  1 0/43 (0.00%)  0
Sinus tachycardia  1  0/21 (0.00%)  0 0/18 (0.00%)  0 1/15 (6.67%)  1 3/81 (3.70%)  5 3/45 (6.67%)  3 5/86 (5.81%)  8 2/43 (4.65%)  4
Tachycardia  1  0/21 (0.00%)  0 0/18 (0.00%)  0 1/15 (6.67%)  1 3/81 (3.70%)  3 2/45 (4.44%)  2 3/86 (3.49%)  3 1/43 (2.33%)  2
Ear and labyrinth disorders               
Ear pain  1  0/21 (0.00%)  0 1/18 (5.56%)  1 1/15 (6.67%)  1 1/81 (1.23%)  1 1/45 (2.22%)  2 0/86 (0.00%)  0 0/43 (0.00%)  0
Endocrine disorders               
Adrenal insufficiency  1  0/21 (0.00%)  0 0/18 (0.00%)  0 1/15 (6.67%)  1 0/81 (0.00%)  0 0/45 (0.00%)  0 0/86 (0.00%)  0 0/43 (0.00%)  0
Hypothyroidism  1  0/21 (0.00%)  0 2/18 (11.11%)  2 0/15 (0.00%)  0 3/81 (3.70%)  5 3/45 (6.67%)  3 0/86 (0.00%)  0 0/43 (0.00%)  0
Eye disorders               
Dry eye  1  1/21 (4.76%)  2 0/18 (0.00%)  0 1/15 (6.67%)  1 2/81 (2.47%)  2 2/45 (4.44%)  2 0/86 (0.00%)  0 0/43 (0.00%)  0
Lacrimation increased  1  1/21 (4.76%)  1 0/18 (0.00%)  0 0/15 (0.00%)  0 4/81 (4.94%)  4 3/45 (6.67%)  3 3/86 (3.49%)  3 3/43 (6.98%)  3
Photopsia  1  0/21 (0.00%)  0 1/18 (5.56%)  1 0/15 (0.00%)  0 0/81 (0.00%)  0 0/45 (0.00%)  0 0/86 (0.00%)  0 0/43 (0.00%)  0
Vision blurred  1  0/21 (0.00%)  0 0/18 (0.00%)  0 1/15 (6.67%)  1 4/81 (4.94%)  5 3/45 (6.67%)  3 2/86 (2.33%)  2 1/43 (2.33%)  1
Gastrointestinal disorders               
Abdominal distension  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 3/81 (3.70%)  3 5/45 (11.11%)  5 1/86 (1.16%)  1 0/43 (0.00%)  0
Abdominal pain  1  2/21 (9.52%)  4 0/18 (0.00%)  0 0/15 (0.00%)  0 9/81 (11.11%)  11 7/45 (15.56%)  12 10/86 (11.63%)  10 6/43 (13.95%)  7
Abdominal pain upper  1  3/21 (14.29%)  3 0/18 (0.00%)  0 0/15 (0.00%)  0 3/81 (3.70%)  5 0/45 (0.00%)  0 2/86 (2.33%)  2 2/43 (4.65%)  2
Anorectal discomfort  1  0/21 (0.00%)  0 1/18 (5.56%)  1 0/15 (0.00%)  0 0/81 (0.00%)  0 1/45 (2.22%)  1 0/86 (0.00%)  0 0/43 (0.00%)  0
Aphthous ulcer  1  0/21 (0.00%)  0 1/18 (5.56%)  1 0/15 (0.00%)  0 0/81 (0.00%)  0 0/45 (0.00%)  0 0/86 (0.00%)  0 0/43 (0.00%)  0
Constipation  1  6/21 (28.57%)  8 3/18 (16.67%)  7 4/15 (26.67%)  6 21/81 (25.93%)  29 12/45 (26.67%)  14 20/86 (23.26%)  24 12/43 (27.91%)  13
Diarrhoea  1  7/21 (33.33%)  22 8/18 (44.44%)  14 5/15 (33.33%)  8 36/81 (44.44%)  84 21/45 (46.67%)  42 30/86 (34.88%)  50 14/43 (32.56%)  21
Dry mouth  1  0/21 (0.00%)  0 0/18 (0.00%)  0 0/15 (0.00%)  0 5/81 (6.17%)  5 6/45 (13.33%)  6 3/86 (3.49%)  3 4/43 (9.30%)  4
Dyspepsia  1  0/21 (0.00%)  0 3/18 (16.67%)  3 1/15 (6.67%)  2 6/81 (7.41%)  9 2/45 (4.44%)  2 8/86 (9.30%)  9 3/43 (6.98%)  3
Gastrooesophageal reflux disease  1  2/21 (9.52%)  2 0/18 (0.00%)  0 1/15 (6.67%)  2 0/81 (0.00%)  0 6/45 (13.33%)