Neoplasms
Conditions
Brief summary
Phase Ib / II study to determine the Maximum Tolerated Dose and Recommended Phase II Dose, and to evaluate the safety and antitumour activity, of BI 836845 and everolimus in combination with exemestane in women with HR+/HER2- advanced breast cancer
Interventions
DRUGEverolimus
10mg dose
DRUGExemestane
Fixed dose at 25mg
DRUGBI 836845
1000 mg, recommended dose per Phase Ib part. Human monoclonal antibody. Dose escalation in Phase Ib. 2 dose levels (high or low) depending on the dose cohort explored
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Histologically-confirmed locally advanced (aBC) or metastatic breast cancer (mBC) not deemed amenable to curative surgery or curative radiation therapy * Tumors are positive for estrogen-receptor (ER) and/or progesterone receptor (PgR). * Tumors must be negative for HER2 per local lab testing. * Must have adequate archival tumor tissue from surgery or biopsy. * Postmenopausal female patients aged \>=18 years old. * Objective evidence of recurrence or progressive disease on or after the last line of systemic therapy for breast cancer prior to study entry * The patient is disease refractory to non-steroidal aromatase inhibitor (letrozole and/or anastrozole) * Patients must have: a) Measurable lesion according to RECIST version 1.1 (R09-0262) or b) Bone lesions: lytic or mixed (lytic + sclerotic) in the absence of measurable lesion as defined above * Eastern Cooperative Oncology Group performance score \<= 2. * Life expectancy of \>= 6 months in the opinion of the investigator * Fasting plasma glucose \< 8.9 mmol/L (\< 160 mg/dL) and HbA1c \< 8.0% * Adequate organ function * Recovered from any previous therapy related toxicity to \<= Grade 1 at study entry (except for stable sensory neuropathy \<=Grade 2 and alopecia) * Written informed consent that is consistent with ICH-GCP guidelines and local regulations Inclusion criteria for the biopsy substudy are identical to the main study of the phase II part except for the following two inclusion criteria: * Fresh tumor biopsy should be taken when deemed safe and feasible by the investigator and upon informed consent by the patient. Bone lesion is not recommended for biopsy * Patients eligible to undergo tumor biopsy should have normal coagulation parameters (INR and PTT within normal range)
Exclusion criteria
* Previous treatment with agents targeting on IGF pathway, phosphoinositide 3-kinase (PI3K) signaling pathway, protein kinase B (AKT), or mammalian target of rapamycin (mTOR) pathways * Prior treatment with exemestane (except adjuvant exemestane stopped \>12 months prior to start of study treatment as long as the patient did not recur during or within 12 months after the end of adjuvant exemestane) * Known hypersensitivity to monoclonal antibody, mTOR inhibitors (e.g. sirolimus), or to the excipients of any study drugs * Ovarian suppression by ovarian radiation or treatment with a luteinizing hormone-releasing hormone (LH-RH) agonist * Less than one week after receiving immunization with attenuated live vaccines prior to study treatment * Radiotherapy within 4 weeks prior to the start of the study treatment, except in case of localized radiotherapy for analgesic purpose or for lytic lesions at risk of fracture which can then be completed within two weeks prior to study treatment * Chemotherapy, biological therapy (other than bevacizumab), immunotherapy or investigational agents within 5 half-life of the drug or within two weeks prior to the start of study treatment, whichever is longer; bevacizumab treatment within 4 weeks prior to start of study treatment (this criterion concerns anti-cancer therapy only) * Hormonal treatment for breast cancer within 2 weeks prior to start of study treatment * Major surgery in the judgement of the investigator within 4 weeks before starting study treatment or scheduled for surgery during the projected course of the study * Patients receiving concomitant immunosuppressive agents or chronic corticosteroids use except Topical applications, inhaled sprays, eye drops or local injections or Patients on stable low dose of corticosteroids for at least two weeks before study entry * Chronic hepatitis B infection, chronic hepatitis C infection and/or known HIV carrier * QTcF prolongation \> 470 ms or QT prolongation deemed clinically relevant by the investigator * Disease that is considered by the investigator to be rapidly progressing or life threatening such as extensive symptomatic visceral disease including hepatic involvement and pulmonary lymphangitic spread of tumor * History or current presence of brain or other CNS metastases * Bilateral diffuse lymphangitic carcinomatosis (in lung) * Hypokalemia of Grade \>1 * History of another primary malignancy within 5 years, with the exception of adequately treated in-situ carcinoma of the cervix, uteri, basal or squamous cell carcinoma or non-melanomatous skin cancer * Family history of long QT syndrome * Any concomitant serious illness or organ system dysfunction which in the opinion of the investigator would either compromise patient safety or interfere with the evaluation of the safety and anti-tumor activity of the test drug(s) * Patients being treated with drugs recognized being strong or moderate CYP3A4 and/or PgP inhibitors and/or strong CYP3A4 inducers within 2 weeks prior to study entry * Patients received more than two lines of chemotherapy for locally advanced or metastatic breast cancer (For the Phase II: more than one line)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) - Phase II Part | From randomisation until radiological tumour progression according to RECIST 1.1, or death from any cause or data cut-off (25Nov2016), up to 30 months. | Progression-free survival (PFS) in the phase II part is presented. Progression-free survival (PFS) was defined as the time from randomisation until radiological tumour progression according to RECIST 1.1, or death from any cause, whichever occurred earlier. Clinical disease progression was not considered for determination of a PFS event, unless the outcome of the progression was death. The cut-off date was 25th November 2016. At cut-off date, xentuzumab was discontinued in all patients in the experimental arm per sponsor decision, recruitment was also terminated. Patients who discontinued xentuzumab treatment continued with everolimus 10 mg + exemestane 25 mg treatment. |
| Number of Patients With Dose Limiting Toxicity (DLT) - Phase Ib Part | From first administration of study treatment until end of first treatment cycle, up to 28 days. | Number of patients with dose limiting toxicity (DLT) in phase Ib part is presented. |
| Maximum Tolerated Dose (MTD) - Phase Ib Part | up to 28 days. | The Maximum Tolerated Dose (MTD) in this study was defined as the highest dose level examined of trial medication, at which no more than 1 out of 6 patients experienced a DLT during the MTD evaluation period. The MTD evaluation period was defined as the time from the first administration of xentuzumab up to start of cycle 2. A 3+3 Phase Ib dose finding phase was performed to determine the MTD. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Objective Response - Phase II Part | From randomisation until first documented complete response (CR) or partial response (PR) or data cut-off (25Nov2016), up to 30 months. | Time to objective response is presented. Time to objective response is defined as the time from randomisation until first documented complete response (CR) or partial response (PR). |
| Number of Patients With Objective Response (OR) - Phase II Part | From randomisation until the earliest of disease progression, death or last evaluable tumour assessment before start of subsequent anti-cancer therapy or data cut-off (25Nov2016), up to 30 months. | Objective response (OR) - phase II part is presented. Objective response (OR), defined as best overall response of complete response (CR) or partial response (PR), where best overall response was determined according to RECIST 1.1 from date of randomisation until the earliest of disease progression, death or last evaluable tumour assessment before start of subsequent anti-cancer therapy. |
| Duration of Disease Control - Phase II Part | From randomisation until the earliest of disease progression or death or data cut-off (25Nov2016), up to 30 months. | Duration of disease control is presented. Duration of disease control is defined as the time from randomisation until the earliest of disease progression or death, among patients with disease control. |
| Duration of Objective Response - Phase II Part | From randomisation until the earliest of disease progression or death or data cut-off (25Nov2016), up to 30 months. | Duration of objective response is presented. Duration of objective response is defined as the time from first documented complete response (CR) or partial response (PR) until the earliest of disease progression or death among patients with objective response (OR). |
| Time to Progression (TTP) - Phase II Part | From randomisation until the date of the first objective tumour progression according to RECIST 1.1. or data cut-off (25Nov2016), up to 30 months. | Time to progression (TTP) is presented. Time to progression (TTP), defined as the time from the date of randomization until the date of the first objective tumour progression according to RECIST 1.1. |
| Number of Patients With Disease Control (DC) - Phase II Part | From randomisation until data cut-off (25Nov2016), up to 30 months. | Disease control is defined as best overall response of complete response (CR) or partial response (PR), or stable disease (SD) \>= 24 weeks, or Non-CR/Non-PD for \>= 24 weeks. PD=Progressive disease. |
Countries
Austria, Belgium, France, Ireland, Netherlands, South Korea, Spain, Sweden, Taiwan, United Kingdom
Participant flow
Recruitment details
This is a phase Ib/II, randomized, open label study to determine the maximum tolerated dose (MTD) and the recommended phase II dose and to evaluate the anti-tumor activity of BI 836845 (xentuzumab) in combination with exemestane and everolimus versus exemestane and everolimus alone in women with locally advanced or metastatic breast cancer.
Pre-assignment details
Only subjects that met all inclusion + none of exclusion criteria were to be entered. Subjects were free to withdraw from clinical trial at any time for any reason given. If subject continued to take trial drug, close monitoring was adhered to + adverse events recorded. Rules were implemented in all trials whereby doses would be reduced if required. If further events were reported, subject would be withdrawn from trial. Symptomatic treatment of tumor associated symptoms were allowed throughout.
Participants by arm
| Arm | Count |
|---|---|
| Xentuzumab (BI 836845) 750 mg + Everolimus 10 mg + Exemestane 25 mg - Phase Ib Subjects received a single dose of 750 milligram (mg) BI 836845 (xentuzumab) as a 1 hour (h) intravenous infusion once a week on Day 1, 8, 15 and 22 in a 28-day course until disease progression, intolerable AEs or other reason necessitating withdrawal.
Subjects also received a single oral dose once daily (qd) of 2x 5 mg (10 mg total) tablets of everolimus and 1 tablet of 25 mg exemestane starting 7 days before first administration of BI 836845 (xentuzumab) continously until disease progression, intolerable AEs or other reason necessitating withdrawal. | 3 |
| Xentuzumab (BI 836845) 1000 mg + Everolimus 10 mg + Exemestane 25 mg - Phase Ib Subjects received a single dose of 1000 milligram (mg) BI 836845 (xentuzumab) as a 1 hour (h) intravenous infusion once a week on Day 1, 8, 15 and 22 in a 28-day course until disease progression, intolerable AEs or other reason necessitating withdrawal.
Subjects also received a single oral dose once daily (qd) of 2x 5 mg (10 mg total) tablets of everolimus and 1 tablet of 25 mg exemestane starting 7 days before first administration of BI 836845 (xentuzumab) continously until disease progression, intolerable AEs or other reason necessitating withdrawal. | 21 |
| Xentuzumab (BI 836845) 1000 mg + Everolimus 10 mg + Exemestane 25 mg - Phase II Subjects received a single dose of 1000 milligram (mg) BI 836845 (xentuzumab) as a 1 hour (h) intravenous infusion once a week on Day 1, 8, 15 and 22 in a 28-day course until disease progression, intolerable AEs or other reason necessitating withdrawal.
Subjects also received a single oral dose once daily (qd) of 2x 5 mg (10 mg total) tablets of everolimus and 1 tablet of 25 mg exemestane starting on Day 1 continously until disease progression, intolerable AEs or other reason necessitating withdrawal.
Administration of xentuzumab was stopped after 28th October 2016, and participants in this group who remained in the trial could continue with everolimus 10 mg + exemestane 25 mg. | 70 |
| Everolimus 10 mg + Exemestane 25 mg - Phase II Subjects received a single oral dose once daily (qd) of 2x 5 mg (10 mg total) tablets of everolimus and 1 tablet of 25 mg exemestane starting on Day 1 continously until disease progression, intolerable AEs or other reason necessitating withdrawal. | 70 |
| Total | 164 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 3 | 5 |
| Overall Study | Lack of Efficacy | 0 | 2 | 8 | 10 |
| Overall Study | Progressive disease | 3 | 19 | 52 | 53 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 7 | 2 |
Baseline characteristics
| Characteristic | Xentuzumab (BI 836845) 750 mg + Everolimus 10 mg + Exemestane 25 mg - Phase Ib | Xentuzumab (BI 836845) 1000 mg + Everolimus 10 mg + Exemestane 25 mg - Phase Ib | Xentuzumab (BI 836845) 1000 mg + Everolimus 10 mg + Exemestane 25 mg - Phase II | Everolimus 10 mg + Exemestane 25 mg - Phase II | Total |
|---|---|---|---|---|---|
| Age, Continuous | 59.00 Years STANDARD_DEVIATION 8 | 64.33 Years STANDARD_DEVIATION 7.84 | 60.17 Years STANDARD_DEVIATION 9.61 | 60.67 Years STANDARD_DEVIATION 9.07 | 60.90 Years STANDARD_DEVIATION 9.17 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 2 Participants | 1 Participants | 5 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 19 Participants | 62 Participants | 57 Participants | 141 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 7 Participants | 8 Participants | 15 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 12 Participants | 12 Participants | 24 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 5 Participants | 7 Participants | 12 Participants |
| Race (NIH/OMB) White | 3 Participants | 21 Participants | 53 Participants | 51 Participants | 128 Participants |
| Sex: Female, Male Female | 3 Participants | 21 Participants | 70 Participants | 70 Participants | 164 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 2 / 21 | 9 / 70 | 11 / 69 |
| other Total, other adverse events | 3 / 3 | 21 / 21 | 70 / 70 | 68 / 69 |
| serious Total, serious adverse events | 3 / 3 | 10 / 21 | 20 / 70 | 29 / 69 |
Outcome results
Primary
Maximum Tolerated Dose (MTD) - Phase Ib Part
The Maximum Tolerated Dose (MTD) in this study was defined as the highest dose level examined of trial medication, at which no more than 1 out of 6 patients experienced a DLT during the MTD evaluation period. The MTD evaluation period was defined as the time from the first administration of xentuzumab up to start of cycle 2. A 3+3 Phase Ib dose finding phase was performed to determine the MTD.
Time frame: up to 28 days.
Population: Maximum tolerated dose (MTD) set: The MTD set defined the set of patients in the Phase Ib part who were fully evaluable for determination of the MTD in the first treatment course. Patients in the TS who were replaced within the MTD evaluation period in the first part of the trial were excluded from the determination of the MTD.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Xentuzumab (BI 836845) 1000 mg + Everolimus 10 mg + Exemestane 25 mg - Phase II | Maximum Tolerated Dose (MTD) - Phase Ib Part | 1000 milligrams (mg) |
Primary
Number of Patients With Dose Limiting Toxicity (DLT) - Phase Ib Part
Number of patients with dose limiting toxicity (DLT) in phase Ib part is presented.
Time frame: From first administration of study treatment until end of first treatment cycle, up to 28 days.
Population: Maximum tolerated dose (MTD) set: The MTD set defined the set of patients in the Phase Ib part who were fully evaluable for determination of the MTD in the first treatment course. Patients in the TS who were replaced within the MTD evaluation period in the first part of the trial were excluded from the determination of the MTD.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Xentuzumab (BI 836845) 1000 mg + Everolimus 10 mg + Exemestane 25 mg - Phase II | Number of Patients With Dose Limiting Toxicity (DLT) - Phase Ib Part | 0 Participants |
| Everolimus 10 mg + Exemestane 25 mg - Phase II | Number of Patients With Dose Limiting Toxicity (DLT) - Phase Ib Part | 1 Participants |
Primary
Progression-free Survival (PFS) - Phase II Part
Progression-free survival (PFS) in the phase II part is presented. Progression-free survival (PFS) was defined as the time from randomisation until radiological tumour progression according to RECIST 1.1, or death from any cause, whichever occurred earlier. Clinical disease progression was not considered for determination of a PFS event, unless the outcome of the progression was death. The cut-off date was 25th November 2016. At cut-off date, xentuzumab was discontinued in all patients in the experimental arm per sponsor decision, recruitment was also terminated. Patients who discontinued xentuzumab treatment continued with everolimus 10 mg + exemestane 25 mg treatment.
Time frame: From randomisation until radiological tumour progression according to RECIST 1.1, or death from any cause or data cut-off (25Nov2016), up to 30 months.
Population: Randomised set (RS): This patient set included all randomised patients in the Phase II part, regardless of whether or not they received treatment. Patients were assigned to xentuzumab (BI 836845) in combination with exemestane and everolimus or exemestane and everolimus alone as randomised.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Xentuzumab (BI 836845) 1000 mg + Everolimus 10 mg + Exemestane 25 mg - Phase II | Progression-free Survival (PFS) - Phase II Part | 7.3 Months |
| Everolimus 10 mg + Exemestane 25 mg - Phase II | Progression-free Survival (PFS) - Phase II Part | 5.6 Months |
p-value: 0.905795% CI: [0.57, 1.65]Log Rank
Secondary
Duration of Disease Control - Phase II Part
Duration of disease control is presented. Duration of disease control is defined as the time from randomisation until the earliest of disease progression or death, among patients with disease control.
Time frame: From randomisation until the earliest of disease progression or death or data cut-off (25Nov2016), up to 30 months.
Population: Randomised set (RS): This patient set included all randomised patients in the Phase II part, regardless of whether or not they received treatment. Patients were assigned to xentuzumab (BI 836845) in combination with exemestane and everolimus or exemestane and everolimus alone as randomised. Only patients with disease control were analysed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Xentuzumab (BI 836845) 1000 mg + Everolimus 10 mg + Exemestane 25 mg - Phase II | Duration of Disease Control - Phase II Part | NA Months |
| Everolimus 10 mg + Exemestane 25 mg - Phase II | Duration of Disease Control - Phase II Part | 9.3 Months |
Secondary
Duration of Objective Response - Phase II Part
Duration of objective response is presented. Duration of objective response is defined as the time from first documented complete response (CR) or partial response (PR) until the earliest of disease progression or death among patients with objective response (OR).
Time frame: From randomisation until the earliest of disease progression or death or data cut-off (25Nov2016), up to 30 months.
Population: Randomised set (RS): This patient set included all randomised patients in the Phase II part, regardless of whether or not they received treatment. Patients were assigned to xentuzumab (BI 836845) in combination with exemestane and everolimus or exemestane and everolimus alone as randomised. Only patients with objective response were analysed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Xentuzumab (BI 836845) 1000 mg + Everolimus 10 mg + Exemestane 25 mg - Phase II | Duration of Objective Response - Phase II Part | 5.6 Months |
| Everolimus 10 mg + Exemestane 25 mg - Phase II | Duration of Objective Response - Phase II Part | NA Months |
Secondary
Number of Patients With Disease Control (DC) - Phase II Part
Disease control is defined as best overall response of complete response (CR) or partial response (PR), or stable disease (SD) \>= 24 weeks, or Non-CR/Non-PD for \>= 24 weeks. PD=Progressive disease.
Time frame: From randomisation until data cut-off (25Nov2016), up to 30 months.
Population: Randomised set (RS): This patient set included all randomised patients in the Phase II part, regardless of whether or not they received treatment. Patients were assigned to xentuzumab (BI 836845) in combination with exemestane and everolimus or exemestane and everolimus alone as randomised.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Xentuzumab (BI 836845) 1000 mg + Everolimus 10 mg + Exemestane 25 mg - Phase II | Number of Patients With Disease Control (DC) - Phase II Part | 13 Participants |
| Everolimus 10 mg + Exemestane 25 mg - Phase II | Number of Patients With Disease Control (DC) - Phase II Part | 17 Participants |
p-value: 0.400895% CI: [0.31, 1.59]Regression, Logistic
Secondary
Number of Patients With Objective Response (OR) - Phase II Part
Objective response (OR) - phase II part is presented. Objective response (OR), defined as best overall response of complete response (CR) or partial response (PR), where best overall response was determined according to RECIST 1.1 from date of randomisation until the earliest of disease progression, death or last evaluable tumour assessment before start of subsequent anti-cancer therapy.
Time frame: From randomisation until the earliest of disease progression, death or last evaluable tumour assessment before start of subsequent anti-cancer therapy or data cut-off (25Nov2016), up to 30 months.
Population: Randomised set (RS): This patient set included all randomised patients in the Phase II part, regardless of whether or not they received treatment. Patients were assigned to xentuzumab (BI 836845) in combination with exemestane and everolimus or exemestane and everolimus alone as randomised.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Xentuzumab (BI 836845) 1000 mg + Everolimus 10 mg + Exemestane 25 mg - Phase II | Number of Patients With Objective Response (OR) - Phase II Part | 5 Participants |
| Everolimus 10 mg + Exemestane 25 mg - Phase II | Number of Patients With Objective Response (OR) - Phase II Part | 7 Participants |
p-value: 0.559895% CI: [0.2, 2.32]Regression, Logistic
Secondary
Time to Objective Response - Phase II Part
Time to objective response is presented. Time to objective response is defined as the time from randomisation until first documented complete response (CR) or partial response (PR).
Time frame: From randomisation until first documented complete response (CR) or partial response (PR) or data cut-off (25Nov2016), up to 30 months.
Population: Randomised set (RS): This patient set included all randomised patients in the Phase II part, regardless of whether or not they received treatment. Patients were assigned to xentuzumab (BI 836845) in combination with exemestane and everolimus or exemestane and everolimus alone as randomised. Only patients with objective response were analysed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Xentuzumab (BI 836845) 1000 mg + Everolimus 10 mg + Exemestane 25 mg - Phase II | Time to Objective Response - Phase II Part | 3.7 Months |
| Everolimus 10 mg + Exemestane 25 mg - Phase II | Time to Objective Response - Phase II Part | 1.8 Months |
Secondary
Time to Progression (TTP) - Phase II Part
Time to progression (TTP) is presented. Time to progression (TTP), defined as the time from the date of randomization until the date of the first objective tumour progression according to RECIST 1.1.
Time frame: From randomisation until the date of the first objective tumour progression according to RECIST 1.1. or data cut-off (25Nov2016), up to 30 months.
Population: Randomised set (RS): This patient set included all randomised patients in the Phase II part, regardless of whether or not they received treatment. Patients were assigned to xentuzumab (BI 836845) in combination with exemestane and everolimus or exemestane and everolimus alone as randomised. Only patients with progression were analysed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Xentuzumab (BI 836845) 1000 mg + Everolimus 10 mg + Exemestane 25 mg - Phase II | Time to Progression (TTP) - Phase II Part | 7.3 Months |
| Everolimus 10 mg + Exemestane 25 mg - Phase II | Time to Progression (TTP) - Phase II Part | 5.6 Months |
p-value: 0.914695% CI: [0.59, 1.8]Log Rank