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The XENERA™ 1 Study Tests Xentuzumab in Combination With Everolimus and Exemestane in Women With Hormone Receptor Positive and HER2-negative Breast Cancer That Has Spread

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ClinicalTrials.gov Identifier: NCT03659136
Recruitment Status : Completed
First Posted : September 6, 2018
Results First Posted : September 29, 2022
Last Update Posted : September 29, 2022
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Breast Neoplasms
Interventions Drug: Xentuzumab
Drug: Placebo
Drug: Everolimus
Drug: Exemestane
Enrollment 103
Recruitment Details A multi-centre, double-blind, placebo-controlled, randomised trial which assess the efficacy of of xentuzumab in combination with everolimus and exemestane over everolimus and exemestane in patients with Hormon Receptor+ (HR+)/ Human epidermal growth factor receptor 2 (HER2)- advanced or metastatic breast cancer and non-visceral disease.
Pre-assignment Details All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist sites which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.
Arm/Group Title 1000 mg Xentuzumab + 10 mg Everolimus + 25 mg Exemestane Placebo + 10 mg Everolimus + 25 mg Exemestane
Hide Arm/Group Description 1000 mg concentrate for solution for infusion of Xentuzumab (BI 836845) (10 mg/mL supplied in 20 mL vials (200 mg/vial)) was administered once weekly as intravenous infusion over 1 hour on day 1, 8, 15 and 22 of 28-days cycles and on day 1, 8, 15, 22, 29, 36, 43 and 50 of 56-day cycles and tablets of Everolimus (Afinitor®) (unit strength 2.5 mg and 5 mg, total dose: 10 mg) and tablets of 25 mg Exemestane (Aromasin®) were administered orally once per day at approximately the same time of day, after a meal. Concentrate for solution for infusion of Placebo was administered once weekly as intravenous infusion of 1 hour on day 1, 8, 15 and 22 of 28-days cycles and on day 1, 8, 15, 22, 29, 36, 43 and 50 of 56-day cycles and tablets of 10 mg of Everolimus (Afinitor®) and tablets of 25 mg Exemestane (Aromasin®) were administered orally once per day at approximately the same time of day, after a meal.
Period Title: Overall Study
Started [1] 52 51
Treated 50 51
Completed 9 12
Not Completed 43 39
Reason Not Completed
COVID-19 related             1             1
Withdrawal by Subject             0             6
Adverse Event             4             7
Progressive disease             34             24
Not treated             2             0
Not specified above             2             1
[1]
Randomised
Arm/Group Title 1000 mg Xentuzumab + 10 mg Everolimus + 25 mg Exemestane Placebo + 10 mg Everolimus + 25 mg Exemestane Total
Hide Arm/Group Description 1000 mg concentrate for solution for infusion of Xentuzumab (BI 836845) (10 mg/mL supplied in 20 mL vials (200 mg/vial)) was administered once weekly as intravenous infusion over 1 hour on day 1, 8, 15 and 22 of 28-days cycles and on day 1, 8, 15, 22, 29, 36, 43 and 50 of 56-day cycles and tablets of Everolimus (Afinitor®) (unit strength 2.5 mg and 5 mg, total dose: 10 mg) and tablets of 25 mg Exemestane (Aromasin®) were administered orally once per day at approximately the same time of day, after a meal. Concentrate for solution for infusion of Placebo was administered once weekly as intravenous infusion of 1 hour on day 1, 8, 15 and 22 of 28-days cycles and on day 1, 8, 15, 22, 29, 36, 43 and 50 of 56-day cycles and tablets of 10 mg of Everolimus (Afinitor®) and tablets of 25 mg Exemestane (Aromasin®) were administered orally once per day at approximately the same time of day, after a meal. Total of all reporting groups
Overall Number of Baseline Participants 52 51 103
Hide Baseline Analysis Population Description
Randomised Set (RS): The randomised set included all randomised patients, regardless of whether they received treatment or not.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 52 participants 51 participants 103 participants
60.9  (11.3) 60.3  (9.6) 60.6  (10.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 52 participants 51 participants 103 participants
Female
52
 100.0%
51
 100.0%
103
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 52 participants 51 participants 103 participants
Hispanic or Latino
3
   5.8%
2
   3.9%
5
   4.9%
Not Hispanic or Latino
43
  82.7%
41
  80.4%
84
  81.6%
Unknown or Not Reported
6
  11.5%
8
  15.7%
14
  13.6%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 52 participants 51 participants 103 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
1
   1.9%
0
   0.0%
1
   1.0%
Native Hawaiian or Other Pacific Islander
1
   1.9%
0
   0.0%
1
   1.0%
Black or African American
0
   0.0%
1
   2.0%
1
   1.0%
White
44
  84.6%
41
  80.4%
85
  82.5%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
6
  11.5%
9
  17.6%
15
  14.6%
1.Primary Outcome
Title Progression Free Survival (PFS)
Hide Description Progression-free survival (PFS) defined as the time from randomisation until progressive disease (PD) according to Response Evaluation Criteria In Solid Tumors (RECIST, version 1.1) in combination with modified MD Anderson Criteria (for bone lesion assessment), based on blinded independent assessment or death from any cause, whichever occurred earlier. As per RECIST, PD is defined as at least a 20% increase in the sum of diameters of target lesions, unequivocal progression of non-target lesions or the appearance of new lesions.
Time Frame From randomisation until the earliest of disease progression, death or the time point of primary PFS analysis, up to 892 days.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomised Set (RS): The randomised set included all randomised patients, regardless of whether they received treatment or not.
Arm/Group Title 1000 mg Xentuzumab + 10 mg Everolimus + 25 mg Exemestane Placebo + 10 mg Everolimus + 25 mg Exemestane
Hide Arm/Group Description:
1000 mg concentrate for solution for infusion of Xentuzumab (BI 836845) (10 mg/mL supplied in 20 mL vials (200 mg/vial)) was administered once weekly as intravenous infusion over 1 hour on day 1, 8, 15 and 22 of 28-days cycles and on day 1, 8, 15, 22, 29, 36, 43 and 50 of 56-day cycles and tablets of Everolimus (Afinitor®) (unit strength 2.5 mg and 5 mg, total dose: 10 mg) and tablets of 25 mg Exemestane (Aromasin®) were administered orally once per day at approximately the same time of day, after a meal.
Concentrate for solution for infusion of Placebo was administered once weekly as intravenous infusion of 1 hour on day 1, 8, 15 and 22 of 28-days cycles and on day 1, 8, 15, 22, 29, 36, 43 and 50 of 56-day cycles and tablets of 10 mg of Everolimus (Afinitor®) and tablets of 25 mg Exemestane (Aromasin®) were administered orally once per day at approximately the same time of day, after a meal.
Overall Number of Participants Analyzed 52 51
Median (95% Confidence Interval)
Unit of Measure: Months
12.7
(6.8 to 29.3)
11.0
(7.7 to 19.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 1000 mg Xentuzumab + 10 mg Everolimus + 25 mg Exemestane, Placebo + 10 mg Everolimus + 25 mg Exemestane
Comments Cox proportional hazards model stratified for presence of baseline bone-only metastases, prior cyclin-dependent kinase (CDK) 4/6 inhibitor treatment and menopause status.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6534
Comments [Not Specified]
Method Log-rank test
Comments Two-sided log-rank test stratified for presence of baseline bone-only metastases, prior (CDK) 4/6 inhibitor treatment and menopause status.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.19
Confidence Interval (2-Sided) 95%
0.55 to 2.59
Estimation Comments Comparison vs. Placebo+Everolimus+Exemestane.
2.Secondary Outcome
Title Overall Survival (OS)
Hide Description

Overall survival (OS) defined as the time from randomisation until death from any cause. For patients with 'event' as an outcome for OS:

OS[days] = date of outcome - date of randomisation + 1.

For patients with 'censored' as an outcome for OS:

OS (censored)[days] = date of outcome - date of randomisation + 1.

Time Frame From randomisation until death from any cause, up to 941 days.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomised Set (RS): The randomised set included all randomised patients, regardless of whether they received treatment or not.
Arm/Group Title 1000 mg Xentuzumab + 10 mg Everolimus + 25 Mgexemestane Placebo + 10 mg Everolimus + 25 mg Exemestane
Hide Arm/Group Description:
1000 mg concentrate for solution for infusion of Xentuzumab (BI 836845) (10mg/mL supplied in 20mL vials (200mg/vial)) was administered once weekly as intravenous infusion over 1 hour on day 1, 8, 15 and 22 of 28-days cycles and on day 1, 8, 15, 22, 29, 36, 43 and 50 of 56-day cycles and tablets of 10 mg of Everolimus (Afinitor®) and tablets of 25 mg Exemestane (Aromasin®) were administered orally once per day at approximately the same time of day, after a meal.
Concentrate for solution for infusion of Placebo was administered once weekly as intravenous infusion of 1 hour on day 1, 8, 15 and 22 of 28-days cycles and on day 1, 8, 15, 22, 29, 36, 43 and 50 of 56-day cycles and tablets of 10 mg of Everolimus (Afinitor®) and tablets of 25 mg Exemestane (Aromasin®) were administered orally once per day at approximately the same time of day, after a meal.
Overall Number of Participants Analyzed 52 51
Median (95% Confidence Interval)
Unit of Measure: Months
NA [1] 
(22.3 to NA)
NA [1] 
(21.1 to NA)
[1]
Median and upper bound of 95% CI could not be estimated due to insufficient events and data immaturity.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 1000 mg Xentuzumab + 10 mg Everolimus + 25 Mgexemestane, Placebo + 10 mg Everolimus + 25 mg Exemestane
Comments Cox proportional hazards model stratified for presence of baseline bone-only metastases, prior cyclin-dependent kinase (CDK) 4/6 inhibitor treatment and menopause status.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1983
Comments [Not Specified]
Method Log rank test
Comments Two-sided log-rank test stratified for presence of baseline bone-only metastases, prior CDK 4/6 inhibitor treatment and menopause status.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.48
Confidence Interval (2-Sided) 95%
0.16 to 1.50
Estimation Comments Comparison vs. Placebo+Everolimus+Exemestane.
3.Secondary Outcome
Title Number of Patients With Disease Control (DC)
Hide Description Disease control (DC) was defined as a best overall response (BOR) of either complete response (CR), partial response (PR), stable disease (SD) or Non-CR/No-PD. SD and Non-CR/Non-PR must have been observed up until at least week 24 tumor assessment. BOR was defined according to RECIST v1.1 in combination with modified MD Anderson Criteria (for bone lesion assessment) based on all evaluable tumor assessments from randomisation until the earliest of PD, start of subsequent anti-cancer therapy, loss to follow-up, withdrawal of consent or death. To be aligned with the primary endpoint derivation, tumor assessments after two or more consecutively misses assessments were not considered. DC was assessed by independent reviewers.
Time Frame From randomisation until the earliest of progressive disease or death from any cause, up to 892 days.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomised Set (RS): The randomised set included all randomised patients, regardless of whether they received treatment or not.
Arm/Group Title 1000 mg Xentuzumab + 10 mg Everolimus + 25 Mgexemestane Placebo + 10 mg Everolimus + 25 mg Exemestane
Hide Arm/Group Description:
1000 mg concentrate for solution for infusion of Xentuzumab (BI 836845) (10mg/mL supplied in 20mL vials (200mg/vial)) was administered once weekly as intravenous infusion over 1 hour on day 1, 8, 15 and 22 of 28-days cycles and on day 1, 8, 15, 22, 29, 36, 43 and 50 of 56-day cycles and tablets of 10 mg of Everolimus (Afinitor®) and tablets of 25 mg Exemestane (Aromasin®) were administered orally once per day at approximately the same time of day, after a meal.
Concentrate for solution for infusion of Placebo was administered once weekly as intravenous infusion of 1 hour on day 1, 8, 15 and 22 of 28-days cycles and on day 1, 8, 15, 22, 29, 36, 43 and 50 of 56-day cycles and tablets of 10 mg of Everolimus (Afinitor®) and tablets of 25 mg Exemestane (Aromasin®) were administered orally once per day at approximately the same time of day, after a meal.
Overall Number of Participants Analyzed 52 51
Measure Type: Count of Participants
Unit of Measure: Participants
29
  55.8%
25
  49.0%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 1000 mg Xentuzumab + 10 mg Everolimus + 25 Mgexemestane, Placebo + 10 mg Everolimus + 25 mg Exemestane
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4932
Comments [Not Specified]
Method Regression, Logistic
Comments Logistic regression model adjusted for presence of baseline bone-only metastases, prior CDK 4/6 inhibitor treatment and menopause status.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.31
Confidence Interval (2-Sided) 95%
0.60 to 2.86
Estimation Comments Comparison vs. Placebo+everolimus+exemestane. An odds ratio >1 indicates a benefit to the xentuzumab arm.
4.Secondary Outcome
Title Duration of Disease Control (DC)
Hide Description

Duration of disease control (DC), defined as the time from randomisation until the earliest of disease progression (according to Response Evaluation Criteria In Solid Tumors (RECIST, version 1.1) in combination with modified MD Anderson Criteria (for bone lesion assessment) or death from any cause, among patients with DC. Duration of DC was assessed by independent reviewers.

The duration of DC was calculated as followed:

For patients with disease progression or death:

Duration of DC [days] = date of outcome - date of randomisation + 1

For patients without disease progression or death:

Duration of DC (censored) [days] = date of outcome - date of randomisation + 1

Time Frame From randomisation until the earliest of progressive disease or death from any cause, up to 892 days.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomised Set (RS): The randomised set included all randomised patients, regardless of whether they received treatment or not. Only participants with disease control are reported.
Arm/Group Title 1000 mg Xentuzumab + 10 mg Everolimus + 25 Mgexemestane Placebo + 10 mg Everolimus + 25 mg Exemestane
Hide Arm/Group Description:
1000 mg concentrate for solution for infusion of Xentuzumab (BI 836845) (10mg/mL supplied in 20mL vials (200mg/vial)) was administered once weekly as intravenous infusion over 1 hour on day 1, 8, 15 and 22 of 28-days cycles and on day 1, 8, 15, 22, 29, 36, 43 and 50 of 56-day cycles and tablets of 10 mg of Everolimus (Afinitor®) and tablets of 25 mg Exemestane (Aromasin®) were administered orally once per day at approximately the same time of day, after a meal.
Concentrate for solution for infusion of Placebo was administered once weekly as intravenous infusion of 1 hour on day 1, 8, 15 and 22 of 28-days cycles and on day 1, 8, 15, 22, 29, 36, 43 and 50 of 56-day cycles and tablets of 10 mg of Everolimus (Afinitor®) and tablets of 25 mg Exemestane (Aromasin®) were administered orally once per day at approximately the same time of day, after a meal.
Overall Number of Participants Analyzed 29 25
Median (95% Confidence Interval)
Unit of Measure: Months
14.6
(9.2 to 29.3)
18.4 [1] 
(9.2 to NA)
[1]
Insufficient events to estimate upper bound of 95% CI for median.
5.Secondary Outcome
Title Number of Participants With Objective Response (OR)
Hide Description Number of participants with objective response (OR) by independent assessment. OR is defined as a best overall response of complete response (CR) or partial response (PR). Best overall response is defined according to RECIST v1.1 in combination with modified MD Anderson Criteria (for bone lesion assessment) and will consider all tumor assessments from randomisation until the earliest of PD, start of subsequent anti-cancer therapy, loss to follow-up, withdrawal of consent or death. To be aligned with the primary endpoint derivation, tumor assessments after two or more consecutively misses assessments were not considered.
Time Frame From randomisation until end of treatment, up to 892 days.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomised Set (RS): The randomised set included all randomised patients, regardless of whether they received treatment or not.
Arm/Group Title 1000 mg Xentuzumab + 10 mg Everolimus + 25 mg Exemestane Placebo + 10 mg Everolimus + 25 mg Exemestane
Hide Arm/Group Description:
1000 mg concentrate for solution for infusion of Xentuzumab (BI 836845) (10 mg/mL supplied in 20 mL vials (200 mg/vial)) was administered once weekly as intravenous infusion over 1 hour on day 1, 8, 15 and 22 of 28-days cycles and on day 1, 8, 15, 22, 29, 36, 43 and 50 of 56-day cycles and tablets of Everolimus (Afinitor®) (unit strength 2.5 mg and 5 mg, total dose: 10 mg) and tablets of 25 mg Exemestane (Aromasin®) were administered orally once per day at approximately the same time of day, after a meal.
Concentrate for solution for infusion of Placebo was administered once weekly as intravenous infusion of 1 hour on day 1, 8, 15 and 22 of 28-days cycles and on day 1, 8, 15, 22, 29, 36, 43 and 50 of 56-day cycles and tablets of 10 mg of Everolimus (Afinitor®) and tablets of 25 mg Exemestane (Aromasin®) were administered orally once per day at approximately the same time of day, after a meal.
Overall Number of Participants Analyzed 52 51
Measure Type: Count of Participants
Unit of Measure: Participants
6
  11.5%
5
   9.8%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 1000 mg Xentuzumab + 10 mg Everolimus + 25 mg Exemestane, Placebo + 10 mg Everolimus + 25 mg Exemestane
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7759
Comments [Not Specified]
Method Regression, Logistic
Comments Logistic regression model adjusted for presence of baseline bone-only metastases, prior CDK 4/6 inhibitor treatment and menopause status.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.20
Confidence Interval (2-Sided) 95%
0.34 to 4.43
Estimation Comments Comparison vs. Placebo+everolimus+exemestane. An odds ratio >1 indicates a benefit to the xentuzumab arm.
6.Secondary Outcome
Title Time to Pain Progression or Intensification of Pain Palliation
Hide Description

Time to pain progression or intensification of pain palliation was defined as the time from randomisation until the earliest of:

  • 2 point increase from baseline in the Brief Pain Inventory - Short Form (BPI-SF), Item 3 (worst pain), without a decrease (of ≥1 point) from baseline analgesics use (via the 8-point Analgesic Quantification Algorithm [AQA]), or
  • 2 point increase from baseline in the AQA, or Death.
Time Frame From randomisation until the earliest of pain progression, intensification of pain palliation, death or the time point of progression free survival analysis, up to 843 days.
Hide Outcome Measure Data
Hide Analysis Population Description
Randomised Set (RS): The randomised set included all randomised patients, regardless of whether they received treatment or not.
Arm/Group Title 1000 mg Xentuzumab + 10 mg Everolimus + 25 Mgexemestane Placebo + 10 mg Everolimus + 25 mg Exemestane
Hide Arm/Group Description:
1000 mg concentrate for solution for infusion of Xentuzumab (BI 836845) (10mg/mL supplied in 20mL vials (200mg/vial)) was administered once weekly as intravenous infusion over 1 hour on day 1, 8, 15 and 22 of 28-days cycles and on day 1, 8, 15, 22, 29, 36, 43 and 50 of 56-day cycles and tablets of 10 mg of Everolimus (Afinitor®) and tablets of 25 mg Exemestane (Aromasin®) were administered orally once per day at approximately the same time of day, after a meal.
Concentrate for solution for infusion of Placebo was administered once weekly as intravenous infusion of 1 hour on day 1, 8, 15 and 22 of 28-days cycles and on day 1, 8, 15, 22, 29, 36, 43 and 50 of 56-day cycles and tablets of 10 mg of Everolimus (Afinitor®) and tablets of 25 mg Exemestane (Aromasin®) were administered orally once per day at approximately the same time of day, after a meal.
Overall Number of Participants Analyzed 52 51
Median (95% Confidence Interval)
Unit of Measure: Months
5.6
(3.2 to 9.3)
3.0 [1] 
(1.9 to NA)
[1]
Insufficient events to estimate upper bound of 95% CI for median.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 1000 mg Xentuzumab + 10 mg Everolimus + 25 Mgexemestane, Placebo + 10 mg Everolimus + 25 mg Exemestane
Comments Cox proportional hazards model stratified for presence of baseline bone-only metastases, prior cyclin-dependent kinase (CDK) 4/6 inhibitor treatment and menopause status.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9279
Comments [Not Specified]
Method Log Rank
Comments Two-sided log-rank test stratified for presence of baseline bone-only metastases, prior CDK4/6 inhibitor treatment and menopause status.
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 0.97
Confidence Interval (2-Sided) 95%
0.54 to 1.76
Estimation Comments Comparison versus Placebo+everolimus+exemestane.
Time Frame [All-cause mortality]: From signing informed consent until end of study, up to 1106 days. [Serious and other adverse events]: From first drug administration until end of treatment + 42 days of residual effect period, up to 924 days.
Adverse Event Reporting Description

[All-cause mortality]: Randomised Set (RS) including all randomised patients, regardless of whether they received treatment or not.

[Serious and other adverse events]: Treated Set (TS) including all patients who are documented to have received and taken at least one dose of any study medication.

 
Arm/Group Title 1000 mg Xentuzumab + 10 mg Everolimus + 25 mg Exemestane Placebo + 10 mg Everolimus + 25 mg Exemestane
Hide Arm/Group Description 1000 mg concentrate for solution for infusion of Xentuzumab (BI 836845) (10 mg/mL supplied in 20 mL vials (200 mg/vial)) was administered once weekly as intravenous infusion over 1 hour on day 1, 8, 15 and 22 of 28-days cycles and on day 1, 8, 15, 22, 29, 36, 43 and 50 of 56-day cycles and tablets of Everolimus (Afinitor®) (unit strength 2.5 mg and 5 mg, total dose: 10 mg) and tablets of 25 mg Exemestane (Aromasin®) were administered orally once per day at approximately the same time of day, after a meal. Concentrate for solution for infusion of Placebo was administered once weekly as intravenous infusion of 1 hour on day 1, 8, 15 and 22 of 28-days cycles and on day 1, 8, 15, 22, 29, 36, 43 and 50 of 56-day cycles and tablets of 10 mg of Everolimus (Afinitor®) and tablets of 25 mg Exemestane (Aromasin®) were administered orally once per day at approximately the same time of day, after a meal.
All-Cause Mortality
1000 mg Xentuzumab + 10 mg Everolimus + 25 mg Exemestane Placebo + 10 mg Everolimus + 25 mg Exemestane
Affected / at Risk (%) Affected / at Risk (%)
Total   5/52 (9.62%)   8/51 (15.69%) 
Hide Serious Adverse Events
1000 mg Xentuzumab + 10 mg Everolimus + 25 mg Exemestane Placebo + 10 mg Everolimus + 25 mg Exemestane
Affected / at Risk (%) Affected / at Risk (%)
Total   13/50 (26.00%)   17/51 (33.33%) 
Blood and lymphatic system disorders     
Anaemia  1  0/50 (0.00%)  1/51 (1.96%) 
Febrile neutropenia  1  1/50 (2.00%)  0/51 (0.00%) 
Cardiac disorders     
Atrial fibrillation  1  0/50 (0.00%)  1/51 (1.96%) 
Cardiac failure  1  1/50 (2.00%)  0/51 (0.00%) 
Endocrine disorders     
Adrenal insufficiency  1  0/50 (0.00%)  1/51 (1.96%) 
Goitre  1  1/50 (2.00%)  0/51 (0.00%) 
Gastrointestinal disorders     
Abdominal pain  1  1/50 (2.00%)  0/51 (0.00%) 
Abdominal pain upper  1  1/50 (2.00%)  0/51 (0.00%) 
Intestinal obstruction  1  0/50 (0.00%)  1/51 (1.96%) 
Nausea  1  1/50 (2.00%)  0/51 (0.00%) 
Proctitis  1  0/50 (0.00%)  1/51 (1.96%) 
Salivary gland calculus  1  0/50 (0.00%)  1/51 (1.96%) 
Vomiting  1  1/50 (2.00%)  0/51 (0.00%) 
General disorders     
Chest pain  1  0/50 (0.00%)  1/51 (1.96%) 
Generalised oedema  1  1/50 (2.00%)  0/51 (0.00%) 
Mucosal inflammation  1  0/50 (0.00%)  1/51 (1.96%) 
Oedema peripheral  1  0/50 (0.00%)  1/51 (1.96%) 
Pyrexia  1  1/50 (2.00%)  0/51 (0.00%) 
Infections and infestations     
Appendicitis  1  1/50 (2.00%)  0/51 (0.00%) 
COVID-19  1  0/50 (0.00%)  1/51 (1.96%) 
COVID-19 pneumonia  1  0/50 (0.00%)  2/51 (3.92%) 
Cellulitis  1  0/50 (0.00%)  1/51 (1.96%) 
Periorbital cellulitis  1  0/50 (0.00%)  1/51 (1.96%) 
Pneumonia  1  1/50 (2.00%)  1/51 (1.96%) 
Tongue abscess  1  1/50 (2.00%)  0/51 (0.00%) 
Urinary tract infection  1  0/50 (0.00%)  1/51 (1.96%) 
Investigations     
Blood creatinine increased  1  0/50 (0.00%)  1/51 (1.96%) 
Metabolism and nutrition disorders     
Hyperglycaemia  1  2/50 (4.00%)  1/51 (1.96%) 
Musculoskeletal and connective tissue disorders     
Bone pain  1  0/50 (0.00%)  1/51 (1.96%) 
Spinal pain  1  1/50 (2.00%)  0/51 (0.00%) 
Tenosynovitis  1  0/50 (0.00%)  1/51 (1.96%) 
Nervous system disorders     
Dizziness  1  0/50 (0.00%)  1/51 (1.96%) 
Lethargy  1  0/50 (0.00%)  1/51 (1.96%) 
Monoparesis  1  0/50 (0.00%)  1/51 (1.96%) 
Psychiatric disorders     
Anxiety  1  0/50 (0.00%)  1/51 (1.96%) 
Mental status changes  1  1/50 (2.00%)  0/51 (0.00%) 
Renal and urinary disorders     
Acute kidney injury  1  0/50 (0.00%)  1/51 (1.96%) 
Dysuria  1  0/50 (0.00%)  1/51 (1.96%) 
Micturition urgency  1  0/50 (0.00%)  1/51 (1.96%) 
Renal failure  1  1/50 (2.00%)  0/51 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  1/50 (2.00%)  0/51 (0.00%) 
Dyspnoea  1  0/50 (0.00%)  1/51 (1.96%) 
Pneumonitis  1  1/50 (2.00%)  3/51 (5.88%) 
Respiratory failure  1  0/50 (0.00%)  1/51 (1.96%) 
Skin and subcutaneous tissue disorders     
Angioedema  1  3/50 (6.00%)  0/51 (0.00%) 
Erythema  1  0/50 (0.00%)  1/51 (1.96%) 
Surgical and medical procedures     
Oophorectomy bilateral  1  0/50 (0.00%)  1/51 (1.96%) 
Vascular disorders     
Jugular vein thrombosis  1  1/50 (2.00%)  0/51 (0.00%) 
1
Term from vocabulary, MedDRA 24.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
1000 mg Xentuzumab + 10 mg Everolimus + 25 mg Exemestane Placebo + 10 mg Everolimus + 25 mg Exemestane
Affected / at Risk (%) Affected / at Risk (%)
Total   48/50 (96.00%)   49/51 (96.08%) 
Blood and lymphatic system disorders     
Anaemia  1  10/50 (20.00%)  13/51 (25.49%) 
Neutropenia  1  9/50 (18.00%)  3/51 (5.88%) 
Thrombocytopenia  1  11/50 (22.00%)  1/51 (1.96%) 
Ear and labyrinth disorders     
Ear pain  1  3/50 (6.00%)  0/51 (0.00%) 
Vertigo  1  5/50 (10.00%)  2/51 (3.92%) 
Eye disorders     
Dry eye  1  5/50 (10.00%)  3/51 (5.88%) 
Lacrimation increased  1  3/50 (6.00%)  1/51 (1.96%) 
Gastrointestinal disorders     
Abdominal pain  1  5/50 (10.00%)  3/51 (5.88%) 
Abdominal pain upper  1  7/50 (14.00%)  3/51 (5.88%) 
Constipation  1  5/50 (10.00%)  8/51 (15.69%) 
Diarrhoea  1  28/50 (56.00%)  17/51 (33.33%) 
Dry mouth  1  5/50 (10.00%)  7/51 (13.73%) 
Dyspepsia  1  4/50 (8.00%)  3/51 (5.88%) 
Haemorrhoids  1  0/50 (0.00%)  3/51 (5.88%) 
Nausea  1  18/50 (36.00%)  14/51 (27.45%) 
Oral pain  1  3/50 (6.00%)  1/51 (1.96%) 
Stomatitis  1  14/50 (28.00%)  15/51 (29.41%) 
Toothache  1  3/50 (6.00%)  0/51 (0.00%) 
Vomiting  1  9/50 (18.00%)  8/51 (15.69%) 
General disorders     
Asthenia  1  10/50 (20.00%)  13/51 (25.49%) 
Chest pain  1  3/50 (6.00%)  4/51 (7.84%) 
Fatigue  1  22/50 (44.00%)  17/51 (33.33%) 
Influenza like illness  1  5/50 (10.00%)  3/51 (5.88%) 
Mucosal inflammation  1  15/50 (30.00%)  16/51 (31.37%) 
Oedema peripheral  1  3/50 (6.00%)  9/51 (17.65%) 
Pain  1  3/50 (6.00%)  5/51 (9.80%) 
Pyrexia  1  7/50 (14.00%)  9/51 (17.65%) 
Infections and infestations     
COVID-19  1  0/50 (0.00%)  4/51 (7.84%) 
Cellulitis  1  1/50 (2.00%)  4/51 (7.84%) 
Gingivitis  1  0/50 (0.00%)  3/51 (5.88%) 
Oral candidiasis  1  0/50 (0.00%)  3/51 (5.88%) 
Tooth abscess  1  0/50 (0.00%)  4/51 (7.84%) 
Upper respiratory tract infection  1  3/50 (6.00%)  3/51 (5.88%) 
Urinary tract infection  1  9/50 (18.00%)  8/51 (15.69%) 
Injury, poisoning and procedural complications     
Contusion  1  7/50 (14.00%)  3/51 (5.88%) 
Fall  1  3/50 (6.00%)  2/51 (3.92%) 
Investigations     
Alanine aminotransferase increased  1  8/50 (16.00%)  7/51 (13.73%) 
Aspartate aminotransferase increased  1  5/50 (10.00%)  8/51 (15.69%) 
Blood albumin decreased  1  3/50 (6.00%)  0/51 (0.00%) 
Blood calcium decreased  1  4/50 (8.00%)  0/51 (0.00%) 
Blood cholesterol increased  1  4/50 (8.00%)  3/51 (5.88%) 
Blood creatine phosphokinase increased  1  7/50 (14.00%)  4/51 (7.84%) 
Blood creatinine increased  1  5/50 (10.00%)  2/51 (3.92%) 
Blood glucose increased  1  4/50 (8.00%)  1/51 (1.96%) 
Blood lactate dehydrogenase increased  1  2/50 (4.00%)  6/51 (11.76%) 
Blood triglycerides increased  1  4/50 (8.00%)  0/51 (0.00%) 
Gamma-glutamyltransferase increased  1  6/50 (12.00%)  4/51 (7.84%) 
Glycosylated haemoglobin increased  1  5/50 (10.00%)  3/51 (5.88%) 
Lymphocyte count decreased  1  3/50 (6.00%)  2/51 (3.92%) 
Neutrophil count decreased  1  4/50 (8.00%)  6/51 (11.76%) 
Platelet count decreased  1  9/50 (18.00%)  5/51 (9.80%) 
Weight decreased  1  7/50 (14.00%)  5/51 (9.80%) 
White blood cell count decreased  1  2/50 (4.00%)  3/51 (5.88%) 
Metabolism and nutrition disorders     
Decreased appetite  1  18/50 (36.00%)  17/51 (33.33%) 
Dehydration  1  2/50 (4.00%)  3/51 (5.88%) 
Hypercholesterolaemia  1  6/50 (12.00%)  1/51 (1.96%) 
Hyperglycaemia  1  10/50 (20.00%)  13/51 (25.49%) 
Hypertriglyceridaemia  1  5/50 (10.00%)  6/51 (11.76%) 
Hypocalcaemia  1  3/50 (6.00%)  2/51 (3.92%) 
Hypokalaemia  1  6/50 (12.00%)  3/51 (5.88%) 
Hypophosphataemia  1  4/50 (8.00%)  4/51 (7.84%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  16/50 (32.00%)  16/51 (31.37%) 
Back pain  1  3/50 (6.00%)  9/51 (17.65%) 
Bone pain  1  4/50 (8.00%)  6/51 (11.76%) 
Muscle spasms  1  12/50 (24.00%)  5/51 (9.80%) 
Musculoskeletal chest pain  1  3/50 (6.00%)  2/51 (3.92%) 
Myalgia  1  6/50 (12.00%)  4/51 (7.84%) 
Neck pain  1  4/50 (8.00%)  3/51 (5.88%) 
Pain in extremity  1  7/50 (14.00%)  6/51 (11.76%) 
Pain in jaw  1  3/50 (6.00%)  1/51 (1.96%) 
Nervous system disorders     
Dizziness  1  8/50 (16.00%)  4/51 (7.84%) 
Dysgeusia  1  10/50 (20.00%)  5/51 (9.80%) 
Headache  1  20/50 (40.00%)  11/51 (21.57%) 
Paraesthesia  1  6/50 (12.00%)  4/51 (7.84%) 
Peripheral sensory neuropathy  1  3/50 (6.00%)  0/51 (0.00%) 
Tremor  1  3/50 (6.00%)  1/51 (1.96%) 
Psychiatric disorders     
Anxiety  1  2/50 (4.00%)  5/51 (9.80%) 
Depression  1  1/50 (2.00%)  3/51 (5.88%) 
Insomnia  1  7/50 (14.00%)  5/51 (9.80%) 
Renal and urinary disorders     
Dysuria  1  4/50 (8.00%)  3/51 (5.88%) 
Pollakiuria  1  4/50 (8.00%)  2/51 (3.92%) 
Proteinuria  1  1/50 (2.00%)  3/51 (5.88%) 
Reproductive system and breast disorders     
Pelvic pain  1  3/50 (6.00%)  0/51 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  12/50 (24.00%)  8/51 (15.69%) 
Dysphonia  1  0/50 (0.00%)  3/51 (5.88%) 
Dyspnoea  1  7/50 (14.00%)  8/51 (15.69%) 
Epistaxis  1  15/50 (30.00%)  7/51 (13.73%) 
Nasal dryness  1  3/50 (6.00%)  1/51 (1.96%) 
Oropharyngeal pain  1  5/50 (10.00%)  2/51 (3.92%) 
Pleural effusion  1  3/50 (6.00%)  0/51 (0.00%) 
Pneumonitis  1  4/50 (8.00%)  12/51 (23.53%) 
Skin and subcutaneous tissue disorders     
Alopecia  1  5/50 (10.00%)  3/51 (5.88%) 
Dermatitis acneiform  1  4/50 (8.00%)  3/51 (5.88%) 
Dry skin  1  6/50 (12.00%)  3/51 (5.88%) 
Eczema  1  0/50 (0.00%)  3/51 (5.88%) 
Erythema  1  6/50 (12.00%)  2/51 (3.92%) 
Pruritus  1  9/50 (18.00%)  9/51 (17.65%) 
Rash  1  13/50 (26.00%)  9/51 (17.65%) 
Rash maculo-papular  1  3/50 (6.00%)  2/51 (3.92%) 
Rash pruritic  1  0/50 (0.00%)  3/51 (5.88%) 
Vascular disorders     
Hypertension  1  6/50 (12.00%)  8/51 (15.69%) 
1
Term from vocabulary, MedDRA 24.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Boehringer Ingelheim
Organization: Boehringer Ingelheim, Call Centre
Phone: 018002430127
EMail: clintriage.rdg@boehringer-ingelheim.com
Layout table for additonal information
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT03659136    
Other Study ID Numbers: 1280-0022
2017-003131-11 ( EudraCT Number )
First Submitted: September 3, 2018
First Posted: September 6, 2018
Results First Submitted: August 10, 2022
Results First Posted: September 29, 2022
Last Update Posted: September 29, 2022