BI 836845 in Estrogen Receptor Positive Metastatic Breast Cancer

NCT02123823 | Completed Phase 1 Results DMC

• 2 other identifiers: 1280.42013-001110-15
• Study Type: interventional
• Target: 164
• Locations: 10 countries
• Sites: 38

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

Conditions

Neoplasms

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

• 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.

  From first administration of study treatment until end of first treatment cycle, up to 28 days.

• 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.

  up to 28 days.

Secondary Outcomes (6)

• 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.

• 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.

• Number of Patients With Disease Control (DC) - Phase II Part

  From randomisation until data cut-off (25Nov2016), up to 30 months.

• 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.

• 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.

Study Arms (4)

everolimus 10 mg + exemestane 25 mg - Phase II

ACTIVE COMPARATOR

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.

Drug: Everolimus; Drug: Exemestane

xentuzumab (BI 836845) 1000 mg + everolimus 10 mg + exemestane 25 mg - Phase II

EXPERIMENTAL

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.

Drug: Everolimus; Drug: Exemestane; Drug: BI 836845

xentuzumab (BI 836845) 750 mg + everolimus 10 mg + exemestane 25 mg - Phase Ib

EXPERIMENTAL

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.

Drug: Everolimus; Drug: Exemestane; Drug: BI 836845

xentuzumab (BI 836845) 1000 mg + everolimus 10 mg + exemestane 25 mg - Phase Ib

EXPERIMENTAL

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.

Drug: Everolimus; Drug: Exemestane; Drug: BI 836845

Interventions

Everolimus DRUG

10mg dose

everolimus 10 mg + exemestane 25 mg - Phase II; xentuzumab (BI 836845) 1000 mg + everolimus 10 mg + exemestane 25 mg - Phase II; xentuzumab (BI 836845) 1000 mg + everolimus 10 mg + exemestane 25 mg - Phase Ib; xentuzumab (BI 836845) 750 mg + everolimus 10 mg + exemestane 25 mg - Phase Ib

Exemestane DRUG

Fixed dose at 25mg

everolimus 10 mg + exemestane 25 mg - Phase II; xentuzumab (BI 836845) 1000 mg + everolimus 10 mg + exemestane 25 mg - Phase II; xentuzumab (BI 836845) 1000 mg + everolimus 10 mg + exemestane 25 mg - Phase Ib; xentuzumab (BI 836845) 750 mg + everolimus 10 mg + exemestane 25 mg - Phase Ib

BI 836845 DRUG

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

Also known as: xentuzumab

xentuzumab (BI 836845) 1000 mg + everolimus 10 mg + exemestane 25 mg - Phase II; xentuzumab (BI 836845) 1000 mg + everolimus 10 mg + exemestane 25 mg - Phase Ib; xentuzumab (BI 836845) 750 mg + everolimus 10 mg + exemestane 25 mg - Phase Ib

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (38)

Medical University of Graz State Hospital - University Hospital Graz

Graz, 8036, Austria

Location

Wilhelminenspital

Vienna, 1160, Austria

Location

Brussels - UNIV UZ Brussel

Brussels, 1090, Belgium

Location

Brussels - UNIV Saint-Luc

Brussels, 1200, Belgium

Location

Charleroi - HOSP Grand Hôpital de Charleroi

Charleroi, 6000, Belgium

Location

Edegem - UNIV UZ Antwerpen

Edegem, 2650, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

Centre Hospitalier Universitaire de Liège

Liège, 4000, Belgium

Location

Liège - HOSP St-Joseph

Liège, 4000, Belgium

Location

CHU UCL Namur - Site De Sainte-Elisabeth

Namur, 5000, Belgium

Location

HOP Jean Minjoz

Besançon, 25030, France

Location

INS Paoli-Calmettes

Marseille, 13009, France

Location

CTR Catherine de Sienne

Nantes, 44202, France

Location

HOP Européen G. Pompidou

Paris, 75015, France

Location

INS Curie

Paris, 75248, France

Location

Ctr Cario

Plerin Sur Mer, 22190, France

Location

St. Vincent's University Hospital

Dublin, D04 T6F4, Ireland

Location

Maastricht University

Maastricht, 6229 HX, Netherlands

Location

National Cancer Center

Goyang, 10408, South Korea

Location

Seoul National University Hospital

Seoul, 110-744, South Korea

Location

Asan Medical Center

Seoul, 138-736, South Korea

Location

Hospital Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Clínic de Barcelona

Barcelona, 08036, Spain

Location

Hospital Arnau de Vilanova

Lleida, 25198, Spain

Location

MD Anderson Cancer Center Madrid

Madrid, 28033, Spain

Location

Hospital Ramón y Cajal

Madrid, 28034, Spain

Location

Hospital Clínico San Carlos

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Virgen del Rocío

Seville, 41013, Spain

Location

Hospital Clínico de Valencia

Valencia, 46010, Spain

Location

Centrummottagningen

Stockholm, 171 76, Sweden

Location

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, 8807, Taiwan

Location

Taichung Veterans General Hospital

Taichung, 40705, Taiwan

Location

National Taiwan University Hospital

Taipei, 10002, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 112, Taiwan

Location

Ninewells Hospital & Medical School

Dundee, DD1 9SY, United Kingdom

Location

St Bartholomew's Hospital

London, EC1M 6BQ, United Kingdom

Location

Freeman Hospital

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

Related Publications (2)

• Dercle L, McGale J, Zhao B, Schmitt J, Peltzer A, Schwartz LH, Amend M. Artificial intelligence and radiomics biomarkers for treatment response prediction in advanced HER2-negative breast cancer. Breast. 2025 Dec;84:104571. doi: 10.1016/j.breast.2025.104571. Epub 2025 Sep 3.

  PMID: 40974664 DERIVED

• Schmid P, Sablin MP, Bergh J, Im SA, Lu YS, Martinez N, Neven P, Lee KS, Morales S, Perez-Fidalgo JA, Adamson D, Goncalves A, Prat A, Jerusalem G, Schlieker L, Espadero RM, Bogenrieder T, Huang DC, Crown J, Cortes J. A phase Ib/II study of xentuzumab, an IGF-neutralising antibody, combined with exemestane and everolimus in hormone receptor-positive, HER2-negative locally advanced/metastatic breast cancer. Breast Cancer Res. 2021 Jan 15;23(1):8. doi: 10.1186/s13058-020-01382-8.

  PMID: 33451345 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Neoplasms

Interventions

Everolimus; exemestane; xentuzumab

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Limitations and Caveats

Xentuzumab was stopped in all patients in the experimental arm per sponsor decision on 28 October 2016 with the implementation of protocol Amendment 3; these patients could continue receiving everolimus plus exemestane. All patients in the experimental arm were to attend for an end of xentuzumab visit (EoXV) after this communication. The EoXV had the same procedures as the end of trial visit (EOTV). Further recruitment was stopped but trial was completed per protocol.

Results Point of Contact

• Title: Boehringer Ingelheim, Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2014
• First Posted: April 28, 2014
• Study Start: May 15, 2014
• Primary Completion: November 25, 2016
• Study Completion: December 14, 2021
• Last Updated: July 15, 2025
• Results First Posted: July 15, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: After all regulatory activities are completed in the US and EU for the product and indication, and after the primary manuscript has been accepted for publication.
• Access Criteria: For study documents - upon signing of a 'Document Sharing Agreement'. For study data - 1. after the submission and approval of the research proposal (checks will be performed by both the independent review panel and the sponsor, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a 'Data Sharing Agreement'.

Locations

ES (9); AU (2); KR (3); NL (1); BE (8); TW (4); FR (6); GB (3); SE (1); IE (1)