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

• ClinicalTrials.gov Identifier: NCT02659020
• Recruitment Status: Completed
• First Posted: January 20, 2016
• Results First Posted: October 11, 2021
• Last Update Posted: May 9, 2022
• Sponsor: Eli Lilly and Company
• 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

Participant Flow

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)
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	18	15	14	65	40	75	35
Not Completed	3	3	1	16	6	11	8
Reason Not Completed
Adverse Event	0	0	0	2	0	0	2
Lost to Follow-up	1	2	1	6	1	5	0
Physician Decision	0	0	0	1	1	0	1
Withdrawal by Subject	2	1	0	3	3	6	3
Progressive Disease	0	0	0	4	1	0	2

Baseline Characteristics

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
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
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

Outcome Measures

1. Primary Outcome

Title	Phase 1b: Number of Participants With Dose Limiting Toxicity (DLT)
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: Febrile neutropenia with documented Grade ≥3 infection or sepsis; Grade 4 neutropenia lasting 7 days or longer.; Grade 4 thrombocytopenia, or Grade 3 thrombocytopenia complicated by hemorrhage.; 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)

Outcome Measure Data

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
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)
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)

Outcome Measure Data

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)
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)

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
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

Outcome Measure Data

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
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
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

Outcome Measure Data

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
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
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

Outcome Measure Data

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
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
Description	Cmax of Gemcitabine.
Time Frame	Day 8 of Cycle 1 (end of infusion, 1, 2, 4, 24 hours post-infusion)

Outcome Measure Data

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
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
Description	AUC[0-∞] of Gemcitabine
Time Frame	Day 8 of Cycle 1 (end of infusion, 1, 2, 4, 24 hours post-infusion)

Outcome Measure Data

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
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
Description	Cmax of Docetaxel.
Time Frame	5 min, 1, 3, 24, 48 h post-dose on Cycle 1 Day 8

Outcome Measure Data

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
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
Description	AUC [0-∞] of Docetaxel.
Time Frame	5 min, 1, 3, 24, 48 h post-dose on Cycle 1 Day 8

Outcome Measure Data

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
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
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

Outcome Measure Data

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
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
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

Outcome Measure Data

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
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)
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)

Outcome Measure Data

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)
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.

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)
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)

Outcome Measure Data

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)
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)

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).

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])
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)

Outcome Measure Data

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)
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)

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).

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)
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)

Outcome Measure Data

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)
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)

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).

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"
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)

Outcome Measure Data

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)
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)

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).

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.
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)

Outcome Measure Data

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)
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.

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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).

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)
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)

Outcome Measure Data

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)
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
Description	Number of Participants with Treatment Emergent Anti-Olaratumab Antibodies
Time Frame	Baseline through Follow-Up (Up to 38 Months)

Outcome Measure Data

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)
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

Adverse Events

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)
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	15/21 (71.43%)		11/18 (61.11%)		12/15 (80.00%)		54/81 (66.67%)		28/45 (62.22%)		58/86 (67.44%)		28/43 (65.12%)
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
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%)	7	5/86 (5.81%)	5	1/43 (2.33%)	1
Haemorrhoids † 1	1/21 (4.76%)	1	0/18 (0.00%)	0	0/15 (0.00%)	0	1/81&nb