Last reviewed · How we verify

NCT02123823

BI 836845 in Estrogen Receptor Positive Metastatic Breast Cancer

Completed Phase 1 Results posted Last updated 15 July 2025
What this trial tests

Phase 1 trial testing Everolimus in Neoplasms in 164 participants. Completed in 14 December 2021.

Timeline
15 May 2014
Primary endpoint
25 November 2016
14 December 2021

Quick facts

Lead sponsorBoehringer Ingelheim
PhasePhase 1
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment164
Start date15 May 2014
Primary completion25 November 2016
Estimated completion14 December 2021
Sites38 locations across France, Netherlands, Belgium, Austria, Sweden, Ireland, Taiwan, United Kingdom

Drugs / interventions tested

Conditions studied

Sponsor

Boehringer Ingelheim — full company profile →

Who can join

Adults 18 to 99, female only, with Neoplasms. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Progression-free Survival (PFS) - Phase II Part Primary · 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 xent

GroupValue95% CI
Xentuzumab (BI 836845) 1000 mg + Everolimus 10 mg + Exemestane 25 mg - Phase II7.33.3 – NA
Everolimus 10 mg + Exemestane 25 mg - Phase II5.63.7 – 9.1
Number of Patients With Dose Limiting Toxicity (DLT) - Phase Ib Part Primary · 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.

GroupValue95% CI
Xentuzumab (BI 836845) 750 mg + Everolimus 10 mg + Exemestane 25 mg - Phase Ib0
Xentuzumab (BI 836845) 1000 mg + Everolimus 10 mg + Exemestane 25 mg - Phase Ib1
Maximum Tolerated Dose (MTD) - Phase Ib Part Primary · 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.

GroupValue95% CI
Xentuzumab (BI 836845)1000
Number of Patients With Objective Response (OR) - Phase II Part Secondary · 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.

GroupValue95% CI
Xentuzumab (BI 836845) 1000 mg + Everolimus 10 mg + Exemestane 25 mg - Phase II52.4 – 15.9
Everolimus 10 mg + Exemestane 25 mg - Phase II74.1 – 19.5
Time to Progression (TTP) - Phase II Part Secondary · 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.

GroupValue95% CI
Xentuzumab (BI 836845) 1000 mg + Everolimus 10 mg + Exemestane 25 mg - Phase II7.33.7 – NA
Everolimus 10 mg + Exemestane 25 mg - Phase II5.65.3 – 9.1
Number of Patients With Disease Control (DC) - Phase II Part Secondary · 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.

GroupValue95% CI
Xentuzumab (BI 836845) 1000 mg + Everolimus 10 mg + Exemestane 25 mg - Phase II1310.3 – 29.7
Everolimus 10 mg + Exemestane 25 mg - Phase II1714.8 – 36.0
Time to Objective Response - Phase II Part Secondary · 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).

GroupValue95% CI
Xentuzumab (BI 836845) 1000 mg + Everolimus 10 mg + Exemestane 25 mg - Phase II3.73.6 – 5.3
Everolimus 10 mg + Exemestane 25 mg - Phase II1.81.7 – 5.3
Duration of Objective Response - Phase II Part Secondary · 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).

GroupValue95% CI
Xentuzumab (BI 836845) 1000 mg + Everolimus 10 mg + Exemestane 25 mg - Phase II5.65.6 – 5.6
Everolimus 10 mg + Exemestane 25 mg - Phase IINANA – NA
Duration of Disease Control - Phase II Part Secondary · 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.

GroupValue95% CI
Xentuzumab (BI 836845) 1000 mg + Everolimus 10 mg + Exemestane 25 mg - Phase IINA10.9 – NA
Everolimus 10 mg + Exemestane 25 mg - Phase II9.39.1 – NA

Adverse events — posted to ClinicalTrials.gov

Time frame: For all AEs including all-cause mortality: Phase Ib: from first dose until last dose + 42 days of residual effect period, up to 54.3 months + 42 days Phase II: from first dose until last dose + 42 days of residual effect period, up to 37.7 months + 42 days. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Xentuzumab (BI 836845) 750 mg + Everolimus 10 mg + Exemestane 25 mg - Phase Ib
Serious: 3/3 (100%)
Deaths: 0/3
Xentuzumab (BI 836845) 1000 mg + Everolimus 10 mg + Exemestane 25 mg - Phase Ib
Serious: 10/21 (48%)
Deaths: 2/21
Xentuzumab (BI 836845) 1000 mg + Everolimus 10 mg + Exemestane 25 mg - Phase II
Serious: 20/70 (29%)
Deaths: 9/70
Everolimus 10 mg + Exemestane 25 mg - Phase II
Serious: 29/69 (42%)
Deaths: 11/69

Serious adverse events (69 terms)

ReactionSystemXentuzumab (BI 836845) 750…Xentuzumab (BI 836845) 100…Xentuzumab (BI 836845) 100…Everolimus 10 mg + Exemest…
Malignant neoplasm progressionNeoplasms benign, malignant and unspecified (incl cysts and polyps)
PneumonitisRespiratory, thoracic and mediastinal disorders
Deep vein thrombosisVascular disorders
PyrexiaGeneral disorders
CholelithiasisHepatobiliary disorders
PneumoniaInfections and infestations
Urinary tract infectionInfections and infestations
Osteonecrosis of jawMusculoskeletal and connective tissue disorders
Acute kidney injuryRenal and urinary disorders
Interstitial lung diseaseRespiratory, thoracic and mediastinal disorders
Pleural effusionRespiratory, thoracic and mediastinal disorders
AnaemiaBlood and lymphatic system disorders
Febrile neutropeniaBlood and lymphatic system disorders
NeutropeniaBlood and lymphatic system disorders
Angina pectorisCardiac disorders
Pericardial effusionCardiac disorders
DeafnessEar and labyrinth disorders
VertigoEar and labyrinth disorders
Abdominal pain upperGastrointestinal disorders
AscitesGastrointestinal disorders
Gastrooesophageal reflux diseaseGastrointestinal disorders
Intestinal obstructionGastrointestinal disorders
SubileusGastrointestinal disorders
VomitingGastrointestinal disorders
AstheniaGeneral disorders
Other adverse events (112 terms — click to expand)

ReactionSystemXentuzumab (BI 836845) 750…Xentuzumab (BI 836845) 100…Xentuzumab (BI 836845) 100…Everolimus 10 mg + Exemest…
DiarrhoeaGastrointestinal disorders
Mucosal inflammationGeneral disorders
StomatitisGastrointestinal disorders
CoughRespiratory, thoracic and mediastinal disorders
RashSkin and subcutaneous tissue disorders
NauseaGastrointestinal disorders
AstheniaGeneral disorders
Decreased appetiteMetabolism and nutrition disorders
NeutropeniaBlood and lymphatic system disorders
FatigueGeneral disorders
Alanine aminotransferase increasedInvestigations
HyperglycaemiaMetabolism and nutrition disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
ThrombocytopeniaBlood and lymphatic system disorders
ArthralgiaMusculoskeletal and connective tissue disorders
HeadacheNervous system disorders
AnaemiaBlood and lymphatic system disorders
Oedema peripheralGeneral disorders
ConstipationGastrointestinal disorders
VomitingGastrointestinal disorders
PruritusSkin and subcutaneous tissue disorders
Aspartate aminotransferase increasedInvestigations
Platelet count decreasedInvestigations
Back painMusculoskeletal and connective tissue disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
Mouth ulcerationGastrointestinal disorders
NasopharyngitisInfections and infestations
Abdominal painGastrointestinal disorders
Blood creatine phosphokinase increasedInvestigations
Weight decreasedInvestigations
HypophosphataemiaMetabolism and nutrition disorders
PyrexiaGeneral disorders
Upper respiratory tract infectionInfections and infestations
HypertriglyceridaemiaMetabolism and nutrition disorders
DysgeusiaNervous system disorders
Urinary tract infectionInfections and infestations
PneumonitisRespiratory, thoracic and mediastinal disorders
HypertensionVascular disorders
Gamma-glutamyltransferase increasedInvestigations
Neutrophil count decreasedInvestigations

Most-reported serious reactions: Malignant neoplasm progression, Pneumonitis, Deep vein thrombosis, Pyrexia, Cholelithiasis, Pneumonia, Urinary tract infection, Osteonecrosis of jaw.

Data from ClinicalTrials.gov NCT02123823 adverse events section.

Sponsor's own description

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

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Chemoresistance in Pancreatic Cancer Is Driven by Stroma-Derived Insulin-Like Growth Factors.
    Ireland L, Santos A, Ahmed MS, Rainer C, et al · · 2016 · cited 203× · PMID 27742686 · DOI 10.1158/0008-5472.can-16-1201
  2. Insulin-like growth factor receptor signaling in tumorigenesis and drug resistance: a challenge for cancer therapy.
    Hua H, Kong Q, Yin J, Zhang J, et al · · 2020 · cited 172× · PMID 32493414 · DOI 10.1186/s13045-020-00904-3
  3. Molecular Pathways: Clinical Applications and Future Direction of Insulin-like Growth Factor-1 Receptor Pathway Blockade.
    Iams WT, Lovly CM. · · 2015 · cited 144× · PMID 26429980 · DOI 10.1158/1078-0432.ccr-14-2518
  4. Therapeutic Targeting of the IGF Axis.
    Osher E, Macaulay VM. · · 2019 · cited 123× · PMID 31416218 · DOI 10.3390/cells8080895
  5. PI3K/AKT/mTOR-Targeted Therapy for Breast Cancer.
    Zhu K, Wu Y, He P, Fan Y, et al · · 2022 · cited 117× · PMID 36010585 · DOI 10.3390/cells11162508
  6. Clinical potential of novel therapeutic targets in breast cancer: CDK4/6, Src, JAK/STAT, PARP, HDAC, and PI3K/AKT/mTOR pathways.
    Hosford SR, Miller TW. · · 2014 · cited 109× · PMID 25206307 · DOI 10.2147/pgpm.s52762
  7. IGF2 Is Up-regulated by Epigenetic Mechanisms in Hepatocellular Carcinomas and Is an Actionable Oncogene Product in Experimental Models.
    Martinez-Quetglas I, Pinyol R, Dauch D, Torrecilla S, et al · · 2016 · cited 98× · PMID 27614046 · DOI 10.1053/j.gastro.2016.09.001
  8. Revisiting the IGF-1R as a breast cancer target.
    Ekyalongo RC, Yee D. · · 2017 · cited 82× · PMID 29152592 · DOI 10.1038/s41698-017-0017-y

Verify or expand the search:

Other trials of Everolimus

Trials testing the same drug.

Other recruiting trials for Neoplasms

Currently open trials in the same condition.

Other Boehringer Ingelheim trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02123823.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing