Neoplasm MetastasisPhase 2NCT03697304
Platform Trial Evaluating Safety and Efficacy of Ezabenlimab Anti- PD-1 Based Combination Therapies in PD-(L)1 naïve and PD- (L)1 Pretreated Patient Populations With Advanced/Metastatic Solid Tumours
A Phase 2 study testing Ezabenlimab, BI 754111 and BI 836880 in people with Neoplasm Metastasis and Advanced Tumors, run by Boehringer Ingelheim at 17 sites in 3 countries.
Trial summary
This is a study in adults with various types of advanced cancer. The purpose of the study is to test a medicine called BI 754091 in combination with several other cancer medicines. BI 754091 is an immunotherapy. This means it may help the immune system fight cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasm Metastasis, Advanced Tumors, Metastatic Solid Tumors
- What is being tested?
- Ezabenlimab, BI 754111 and BI 836880
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 211 participants
- Where
- 17 sitesin 3 countries
- Study dates
- 19 Mar 2019to 3 Dec 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Master Protocol:
- Provision of signed and dated, written Master informed consent form (ICF) prior to any trial-specific procedures, sampling, or analyses.
- Patient ≥18 years of age at the time of signature of the ICF.
- Eastern Cooperative Oncology Group (ECOG) score: 0 or 1.
- Patient must agree to a pre-treatment biopsy (if archival tissue is not available) and on-treatment tumour biopsy. If archived tumour tissue is available from the last treatment failure, sections may be supplied instead of a pre-treatment biopsy.
- Life expectancy of at least 12 weeks after the start of the treatment according to the Investigator's judgement.
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- Male or female patients. Women of childbearing potential (WOCBP) and men able to father a child must be willing and able to use highly effective methods of birth control (that result in a low failure rate of less than 1% per year when used consistently and correctly) during trial participation and for at least 6 months after the last administration of trial medication. Acceptable highly effective methods of contraception include total sexual abstinence when this is in line with the preferred and usual lifestyle of the study participant (periodic abstinence such as calendar, ovulation, symptothermal, post-ovulation methods and withdrawal are not acceptable methods of contraception), an intrauterine device or intrauterine hormone-releasing system, bilateral tubal ligation, and vasectomised partner (with post-vasectomy proof of absence of sperm). Male patients with partners of childbearing potential must agree to use condoms and ensure their partners are using an additional highly effective method of birth control, during the trial and until at least 6 months after the end of the trial treatment.
- Module A:
- Histologically confirmed diagnosis of one of the following cohorts:
- Cohort 1 GEC - Locally advanced, unresectable or metastatic gastric adenocarcinoma or gastro oesophageal adenocarcinoma (GEC) (defined as primary tumour localisation below the gastro oesophageal junction (GEJ) with prior anti-PD-1 or anti-PD-L1 based treated tumour.
- Cohort 2 Patients with secondary resistance to anti-PD-1 or anti-PD-L1 based therapy: Any advanced or metastatic solid tumour with previously anti-PD-1 or anti-PD-L1 based treatment who progressed after achieving benefit
- Cohort 3 Patients with primary resistance to anti-PD-1 or anti-PD-L1 based therapy: Select advanced or metastatic solid tumour types with previous anti-PD- 1/PD-L1 based treated tumour without achieving benefit.
- All patients must have measurable lesions according to RECIST v1.1
- Patient must agree to pre- and on-treatment tumour biopsies. If archived tumour tissue is available from the last treatment failure, sections may be supplied instead of a pre-treatment biopsy.
- Module C:
- Histologically confirmed diagnosis of one of the following cohorts:
- Cohort 1: GEC: Locally advanced, unresectable or metastatic gastric adenocarcinoma or GEC.
- Cohort 2: Patients with secondary resistance to anti-PD-1 or anti-PD-L1 based therapy: Any advanced or metastatic solid tumour (excluding NSCLC and melanoma) with previously anti-PD-1 or anti-PD-L1 based treatment which progressed after achieving benefit.
- Cohort 3: Patients with primary resistance to anti-PD-1 or anti-PD-L1 based therapy: Select advanced or metastatic solid tumour types with previous anti-PD-1/PD-L1 based treated tumour without achieving benefit.
- Cohort 4: Locally advanced, unresectable or metastatic second line or greater, microsatellite stable (MSS) colorectal cancer.
- Cohort 5: Advanced Endometrial cancer: Endometrial carcinoma that is pMMR (Mismatch Repair-Proficient)/MSS and is advanced, recurrent, or persistent and has relapsed or is refractory to curative therapy.
- All patients must have at least one measurable lesion according to RECIST v1.1
- Further inclusion criteria apply
Who cannot join
- Master Protocol:
- Any investigational treatment anti-tumour treatment within 4 weeks or within 5 half-life periods (whichever is shorter) prior to the initiation of trial treatment.
- More than one anti-PD-(L)1-based treatment regimen prior to entering study study, more specifically defined in the modules. Note: once in a trial Module, patients may crossover to different Module if all other eligibility criteria are met.
- Major surgery ('major' according to the Investigator's assessment) performed within 12 weeks prior to first trial treatment or planned within 12 months after screening, e.g., hip replacement.
- Known history of severe hypersensitivity reactions to other mAbs or known hypersensitivity to the trial drugs or their excipients.
- Presence of central nervous system (CNS) metastases, unless treated and asymptomatic and off corticosteroids and/or anticonvulsant therapy for at least 2 weeks prior to start of treatment.
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- Immunosuppressive corticosteroid doses (>10 mg prednisone daily or equivalent) within 4 weeks prior to the first dose of study treatment.
- Active autoimmune disease or a documented history of autoimmune disease, except vitiligo or resolved childhood asthma/atopy. Patients who were permanently discontinued from previous anti-PD-1 or anti-PD-L1 therapy because of an immune-related adverse event (irAE).
- Module A:
- Previous treatment with an anti-LAG-3 Agent
- Module C:
- Unresolved, Grade >1 toxicity before the start of treatment with the study drug except for hair loss (alopecia) and hypothyroidism that requires thyroid hormone supplements but is asymptomatic under therapy.
- Significant cardiovascular/cerebrovascular diseases (i.e. uncontrolled hypertension, unstable angina, history of infarction within past 6 months, congestive heart failure > New York Heart Association [NYHA] II)
- History of severe haemorrhagic or thromboembolic event in the past 12 months
- Known inherited predisposition to bleeding or to thrombosis, in the opinion of the investigator - Further exclusion criteria apply
Trial locations and contacts
17 sites in 3 countries.
17 sites in 3 countries
United States11 sites
Tennessee Oncology
Chattanooga, Tennessee, 37404
Florida Cancer Specialists-Fort Myers-52980
Fort Myers, Florida, 33901
Indiana University
Indianapolis, Indiana, 46202
University of California San Diego
La Jolla, California, 92093
Norton Cancer Institute
Louisville, Kentucky, 40202
Medical College Of Wisconsin
Milwaukee, Wisconsin, 53226
Tennessee Oncology, PLLC-Nashville-52568
Nashville, Tennessee, 37203
Oklahoma University School of Community Medicine
Oklahoma City, Oklahoma, 73104
Florida Cancer Specialists-Saint Petersburg-52979
St. Petersburg, Florida, 33705
Florida Cancer Specialists-Sarasota-61670
Tallahassee, Florida, 32308
Florida Cancer Specialists - East
West Palm Beach, Florida, 33401
United Kingdom4 sites
Beatson West of Scotland Cancer Centre
Glasgow, G12 0YN
University College Hospital
London, NW1 2BU
Guy's Hospital
London, SE1 9RT
Sarah Cannon Research Institute, London
London, W1G 6AD
Canada2 sites
Cross Cancer Institute (University of Alberta)
Edmonton, Alberta, T6G 1Z2
Princess Margaret Cancer Centre
Toronto, Ontario, M5G 1Z6
About this study
Official title: An Open-label, Phase II, Platform Trial Evaluating Safety and Efficacy of Multiple BI 754091 (Ezabenlimab) Anti-PD-1 Based Combination Regimens in PD-(L)1 naïve and PD-(L)1 Pretreated Patient Populations With Advanced and/or Metastatic Solid Tumours Who Have Had at Least One Line of Systemic Therapy
This is a study in adults with various types of advanced cancer. The purpose of the study is to test a medicine called BI 754091 in combination with several other cancer medicines. BI 754091 is an immunotherapy. This means it may help the immune system fight cancer. Such therapies are also called immune checkpoint inhibitors.
How long the participants are in the study depends on whether they benefit from treatment and whether they experience unacceptable side effects. The participants are put into different groups. Each group receives BI 754091 in combination with another medicine.
The doctors check whether the tumors shrink or disappear. The doctors also check the general health of the participants.
- Being tested
- Ezabenlimab, BI 754111, BI 836880
- Medical subject headings
- Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EzabenlimabDrug
Also called BI 754091
240 mg of ezabenlimab (BI 754091), intravenously, on Day 1 of 21-day cycles.
BI 754111Drug
600 mg of BI 754111, intravenously, on Day 1 of 21-day cycles.
BI 836880Drug
720 mg of BI 836880, intravenously, on Day 1 of 21-day cycles.
| Study group | Role | What they receive |
|---|---|---|
| Module C, Cohort 1: GEC patients | Experimental | Patients with locally advanced, unresectable or metastatic gastric adenocarcinoma or gastro-oesophageal adenocarcinoma (GEC) with at least one prior systemic treatment, who failed standard therapy, for whom no further effective options existed, and with no prior PD-1 or PD-L1-based treatment, were administered 240 mg of ezabenlimab (BI 754091), intravenously, on Day 1 of 21-day cycles, along with 720 mg of BI 836880, in the form of i.v. infusion, on Day 1 of 21-day cycles. Receives: Drug: Ezabenlimab; Drug: BI 836880 |
| Module C, Cohort 2: 2ary resistance patients | Experimental | Patients with any advanced or metastatic solid tumor (excluding non-squamous lung cancer, non-small-cell lung cancer, and melanoma) who had received prior anti-PD-1- or anti-PD-L1-based treatment and progressed after achieving benefit (at least stable disease with a minimum duration of benefit of 4 months) and minimum treatment duration of 2 months on the previous anti-PD-1- or anti-PD-L1-based treatment without progressive disease, were administered 240 mg of ezabenlimab (BI 754091), intravenously, on Day 1 of 21-day cycles, along 720 mg of BI 836880 on Day 1, intravenously, on Day1 of 21-day cycles. Receives: Drug: Ezabenlimab; Drug: BI 836880 |
| Module C, Cohort 3: 1ary resistance patients | Experimental | Patients with select advanced or metastatic solid tumors with prior anti-PD-1- or anti-PD-L1-based treatment without achieving benefit ( stable disease duration of less than 4 months or progressive disease in less than 4 months while on treatment), were administered 240 mg of ezabenlimab (BI 754091), intravenously, on Day 1 of 21-day cycles, along with 720 mg of BI 836880, intravenously, on Day 1 of 21-day cycles. Receives: Drug: Ezabenlimab; Drug: BI 836880 |
| Module C, Cohort 4: CRC patients | Experimental | Patients with locally advanced, unresectable or metastatic second-line or greater, microsatellite-stable colorectal cancer (CRC) without prior anti-PD-1- or anti-PD-L1-based treatment, were administered 240 mg of ezabenlimab (BI 754091), intravenously, on Day 1 of 21-day cycles, along with 720 mg of BI 836880, intravenously, on Day 1 of 21-day cycles. Receives: Drug: Ezabenlimab; Drug: BI 836880 |
| Module C, Cohort 5: EC patients | Experimental | Patients with advanced endometrial carcinoma (EC), excluding microsatellite instability-high or mismatch repair deficient types, who progressed following one line of chemotherapy, were not eligible for curative surgery or radiation, and had not been previously treated with anti-PD-1- or anti-PD-L1-based therapies, were administered 240 mg of ezabenlimab (BI 754091), intravenously, on Day 1 of 21-day cycles, along with 720 mg of BI 836880, intravenously, on Day 1 of 21-day cycles. Receives: Drug: Ezabenlimab; Drug: BI 836880 |
| Module A, Cohort 1: GEC patients | Experimental | Patients with locally advanced, unresectable or metastatic gastric adenocarcinoma or gastro-oesophageal adenocarcinoma, who received prior anti-PD-1 or anti-PD-L1-based treatment, were administered 240 mg of ezabenlimab (BI 754091), intravenously, on Day 1 of 21-day cycles, along with 600 mg of BI 754111, intravenously, on Day 1 of 21-day cycles. Receives: Drug: Ezabenlimab; Drug: BI 754111 |
| Module A, Cohort 2: 2ary resistance patients | Experimental | Patients with any advanced or metastatic solid tumors who had been previously treated with anti-PD-1 or anti-PD-L1-based therapies, and who progressed after achieving benefit (at least stable disease with a minimum duration of benefit of 6 months) and minimum treatment duration of 2 months without experiencing disease progression, were administered 240 mg of ezabenlimab (BI 754091), intravenously, on Day 1 of 21-day cycles, along with 600 mg of BI 754111, intravenously, on Day 1 of 21-day cycles. Receives: Drug: Ezabenlimab; Drug: BI 754111 |
| Module A, Cohort 3: 1ary resistance patients | Experimental | Patients with select advanced or metastatic solid tumor types, who have been previously treated with previous anti-PD-1 or anti-PD-L1-based therapies without achieving benefit (stable disease for less than 6 months or progressive disease in less than 6 months), were administered 240 mg of ezabenlimab (BI 754091), intravenously, on Day 1 of 21-day cycles, along with 600 mg of BI 754111, intravenously, on Day 1 of 21-day cycles. Receives: Drug: Ezabenlimab; Drug: BI 754111 |
What is being measured
The primary outcome is the main question the study is designed to answer.
[Module C] Objective Response (OR)
Confirmed objective response (OR), defined as the percentage of participants with best overall response of complete response (CR) or partial response (PR), assessed by the investigator according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1 (v1.1). Complete response (CR) was defined as the disappearance of all target lesions and partial response (PR) was defined as decrease of at least 30% in the sum of the diameter of target lesions taking the baseline sum diameters as reference.
Measured: From first drug administration until the earliest of disease progression, death or last evaluable tumor assessment before start of subsequent anti-cancer therapy. Up to approximately 188.3 weeks.
[Module C] Objective Response (OR) - Bayesian Hierarchical Model
Confirmed objective response (OR), defined as the objective response rate (ORR) of participants with best overall response of complete response (CR) or partial response (PR), assessed by the investigator according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1 (v1.1). Complete response (CR) was defined as the disappearance of all target lesions and partial response (PR) was defined as decrease of at least 30% in the sum of the diameter of target lesions taking the baseline sum diameters as reference. The estimated objective response rate is presented by the posterior medians of the Bayesian hierarchical model and by the correspondent credible intervals.
Measured: From first drug administration until the earliest of disease progression, death or last evaluable tumor assessment before start of subsequent anti-cancer therapy. Up to approximately 188.3 weeks.
[Module A] Objective Response (OR)
Confirmed objective response (OR), defined as the percentage of participants with best overall response of complete response (CR) or partial response (PR), assessed by the investigator according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1 (v1.1). Complete response (CR) was defined as the disappearance of all target lesions and partial response (PR) was defined as decrease of at least 30% in the sum of the diameter of target lesions taking the baseline sum diameters as reference.
Measured: From first drug administration until the earliest of disease progression, death or last evaluable tumor assessment before start of subsequent anti-cancer therapy. Up to approximately 152.4 weeks.
[Module A] Objective Response (OR) - Bayesian Hierarchical Model
Confirmed objective response (OR), defined as the objective response rate (ORR) of participants with best overall response of complete response (CR) or partial response (PR), assessed by the investigator according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1 (v1.1). Complete response (CR) was defined as the disappearance of all target lesions and partial response (PR) was defined as decrease of at least 30% in the sum of the diameter of target lesions taking the baseline sum diameters as reference. The estimated objective response rate is presented by the posterior medians of the Bayesian hierarchical model and by the correspondent credible intervals.
Measured: From first drug administration until the earliest of disease progression, death or last evaluable tumor assessment before start of subsequent anti-cancer therapy. Up to approximately 152.4 weeks.
Secondary outcomes (8)
[Module C] Duration of Response (DoR)
Duration of response (DoR) was defined as the time from first documented complete response (CR) or partial response (PR) (RECIST v1.1) among patients with objective response (OR), according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1 (v1.1). Complete response (CR) was defined as the disappearance of all target lesions and partial response (PR) was defined as decrease of at least 30% in the sum of the diameter of target lesions taking the baseline sum diameters as reference. DoR parameters were calculated based on Kaplan-Meier estimation. The analysis was performed on the unconfirmed OR.
Measured: From first documented CR or PR (RECIST v1.1) until the earlier of disease progression or death. Up to 174.6 weeks.
[Module C] Disease Control (DC)
Disease Control (DC) defined as the percentage of patients with best overall response of complete response (CR), partial response (PR), or stable disease (SD), assessed by the investigator according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1 (v1.1). CR was defined as the disappearance of all target lesions, PR was defined as decrease of at least 30% in the sum of the diameter of target lesions taking the baseline sum diameters as reference, SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study, and PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study.
Measured: From first drug administration until the earliest of disease progression, death or last evaluable tumor assessment before start of subsequent anti-cancer therapy. Up to approximately 188.3 weeks.
[Module C] Disease Control (DC) - Bayesian Hierarchical Model
Disease Control (DC), defined as the disease control rate (DCR) of participants with best overall response of complete response (CR), partial response (PR), or stable disease (SD), assessed by the investigator according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1 (v1.1). CR was defined as the disappearance of all target lesions, PR was defined as decrease of at least 30% in the sum of the diameter of target lesions taking the baseline sum diameters as reference, SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study, and PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. The estimated DCR is presented by the posterior medians of the bayesian hierarchical model and by the correspondent credible intervals.
Measured: From first drug administration until the earliest of disease progression, death or last evaluable tumor assessment before start of subsequent anti-cancer therapy. Up to approximately 188.3 weeks.
[Module C] Progression-free Survival (PFS)
Progression-free survival (PFS) was defined as the time from first treatment administration until progressive disease (PD), according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1 (v1.1), or death from any cause, whichever occurred earlier. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. PFS parameters were calculated based on Kaplan-Meier estimation.
Measured: From first drug administration until PD or death, whichever occurred earlier. Up to approximately 186.1 weeks.
[Module A] Duration of Response (DoR)
Duration of response (DoR) was defined as the time from first documented complete response (CR) or partial response (PR) (RECIST v1.1) among patients with objective response (OR), according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1 (v1.1). Complete response (CR) was defined as the disappearance of all target lesions and partial response (PR) was defined as decrease of at least 30% in the sum of the diameter of target lesions taking the baseline sum diameters as reference. DoR parameters were calculated based on Kaplan-Meier estimation. The analysis was performed on the unconfirmed OR.
Measured: From first documented CR or PR (RECIST v1.1) until the earlier of disease progression or death. Up to 63.6 weeks.
[Module A] Disease Control (DC)
Disease Control (DC) defined as the percentage of patients with best overall response of complete response (CR), partial response (PR), or stable disease (SD), assessed by the investigator according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1 (v1.1). CR was defined as the disappearance of all target lesions, PR was defined as decrease of at least 30% in the sum of the diameter of target lesions taking the baseline sum diameters as reference, SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study, and PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study.
Measured: From first drug administration until the earliest of disease progression, death or last evaluable tumor assessment before start of subsequent anti-cancer therapy. Up to approximately 152.4 weeks.
[Module A] Disease Control (DC) - Bayesian Hierarchical Model
Disease Control (DC), defined as the disease control rate (DCR) of participants with best overall response of complete response (CR), partial response (PR), or stable disease (SD), assessed by the investigator according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1 (v1.1). CR was defined as the disappearance of all target lesions, PR was defined as decrease of at least 30% in the sum of the diameter of target lesions taking the baseline sum diameters as reference, SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study, and PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. The estimated DCR is presented by the posterior medians of the bayesian hierarchical model and by the correspondent credible intervals.
Measured: From first drug administration until the earliest of disease progression, death or last evaluable tumor assessment before start of subsequent anti-cancer therapy. Up to approximately 152.4 weeks.
[Module A] Progression-free Survival (PFS)
Progression-free survival (PFS) was defined as the time from first treatment administration until progressive disease (PD), according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1 (v1.1), or death from any cause, whichever occurred earlier. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. PFS parameters were calculated based on Kaplan-Meier estimation. Progression free survival was collected, according to the clinical trial protocol until July 2021.
Measured: From first drug administration until PD, death, or cut-off date of July 2021, whichever occurred earlier. Up to approximately 104.7 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Oct 2018
- Study start19 Mar 2019
- Primary completion3 Dec 2024
- Study completion3 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Neoplasm MetastasisStudies of the same condition, open and under way.
- More trials run by Boehringer IngelheimThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 211 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boehringer Ingelheim
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03697304
- Sponsor's protocol ID
- 1381-0009
- Other IDs
- 2018-002344-81, 2018
- Status last verified
- Jan 2026
- First submitted
- 2 Oct 2018
- Last updated
- 27 Jan 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents. Exceptions might apply, e.g. studies in products where Boehringer Ingelheim is not the license holder; studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; studies conducted in a single center or targeting rare diseases(in case of low number of patients and therefore limitations with anonymization). For more details refer to: https://www.mystudywindow.com/msw/datatransparency
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Phase II, Platform Trial Evaluating Safety and Efficacy of Multiple BI 754091 (Ezabenlimab) Anti-PD-1 Based Combination Regimens in PD-(L)1 naïve and PD-(L)1 Pretreated Patient Populations With Advanced and/or Metastatic Solid Tumours Who Have Had at Least One Line of Systemic Therapy
- ClinicalTrials.gov ID
- NCT03697304
- Acronym / sponsor ID
- 1381-0009
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 211 participants (actual)
- Lead sponsor
- Boehringer IngelheimIndustry (pharma, biotech, devices)
- Study start
- 19 Mar 2019 (actual)
- Primary completion
- 3 Dec 2024 (actual)
- Study completion
- 3 Dec 2024 (actual)
- First posted
- 5 Oct 2018 (actual)
- Results
- Posted 27 Jan 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a study in adults with various types of advanced cancer. The purpose of the study is to test a medicine called BI 754091 in combination with several other cancer medicines. BI 754091 is an immunotherapy. This means it may help the immune system fight cancer. Such therapies are also called immune checkpoint inhibitors.
How long the participants are in the study depends on whether they benefit from treatment and whether they experience unacceptable side effects. The participants are put into different groups. Each group receives BI 754091 in combination with another medicine.
The doctors check whether the tumors shrink or disappear. The doctors also check the general health of the participants.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| Module C, Cohort 1: GEC patients | Experimental | Drug: Ezabenlimab, Drug: BI 836880Patients with locally advanced, unresectable or metastatic gastric adenocarcinoma or gastro-oesophageal adenocarcinoma (GEC) with at least one prior systemic treatment, who failed standard therapy, for whom no further effective options existed, and with no prior PD-1 or PD-L1-based treatment, were administered 240 mg of ezabenlimab (BI 754091), intravenously, on Day 1 of 21-day cycles, along with 720 mg of BI 836880, in the form of i.v. infusion, on Day 1 of 21-day cycles. |
| Module C, Cohort 2: 2ary resistance patients | Experimental | Drug: Ezabenlimab, Drug: BI 836880Patients with any advanced or metastatic solid tumor (excluding non-squamous lung cancer, non-small-cell lung cancer, and melanoma) who had received prior anti-PD-1- or anti-PD-L1-based treatment and progressed after achieving benefit (at least stable disease with a minimum duration of benefit of 4 months) and minimum treatment duration of 2 months on the previous anti-PD-1- or anti-PD-L1-based treatment without progressive disease, were administered 240 mg of ezabenlimab (BI 754091), intravenously, on Day 1 of 21-day cycles, along 720 mg of BI 836880 on Day 1, intravenously, on Day1 of 21-day cycles. |
| Module C, Cohort 3: 1ary resistance patients | Experimental | Drug: Ezabenlimab, Drug: BI 836880Patients with select advanced or metastatic solid tumors with prior anti-PD-1- or anti-PD-L1-based treatment without achieving benefit ( stable disease duration of less than 4 months or progressive disease in less than 4 months while on treatment), were administered 240 mg of ezabenlimab (BI 754091), intravenously, on Day 1 of 21-day cycles, along with 720 mg of BI 836880, intravenously, on Day 1 of 21-day cycles. |
| Module C, Cohort 4: CRC patients | Experimental | Drug: Ezabenlimab, Drug: BI 836880Patients with locally advanced, unresectable or metastatic second-line or greater, microsatellite-stable colorectal cancer (CRC) without prior anti-PD-1- or anti-PD-L1-based treatment, were administered 240 mg of ezabenlimab (BI 754091), intravenously, on Day 1 of 21-day cycles, along with 720 mg of BI 836880, intravenously, on Day 1 of 21-day cycles. |
| Module C, Cohort 5: EC patients | Experimental | Drug: Ezabenlimab, Drug: BI 836880Patients with advanced endometrial carcinoma (EC), excluding microsatellite instability-high or mismatch repair deficient types, who progressed following one line of chemotherapy, were not eligible for curative surgery or radiation, and had not been previously treated with anti-PD-1- or anti-PD-L1-based therapies, were administered 240 mg of ezabenlimab (BI 754091), intravenously, on Day 1 of 21-day cycles, along with 720 mg of BI 836880, intravenously, on Day 1 of 21-day cycles. |
| Module A, Cohort 1: GEC patients | Experimental | Drug: Ezabenlimab, Drug: BI 754111Patients with locally advanced, unresectable or metastatic gastric adenocarcinoma or gastro-oesophageal adenocarcinoma, who received prior anti-PD-1 or anti-PD-L1-based treatment, were administered 240 mg of ezabenlimab (BI 754091), intravenously, on Day 1 of 21-day cycles, along with 600 mg of BI 754111, intravenously, on Day 1 of 21-day cycles. |
| Module A, Cohort 2: 2ary resistance patients | Experimental | Drug: Ezabenlimab, Drug: BI 754111Patients with any advanced or metastatic solid tumors who had been previously treated with anti-PD-1 or anti-PD-L1-based therapies, and who progressed after achieving benefit (at least stable disease with a minimum duration of benefit of 6 months) and minimum treatment duration of 2 months without experiencing disease progression, were administered 240 mg of ezabenlimab (BI 754091), intravenously, on Day 1 of 21-day cycles, along with 600 mg of BI 754111, intravenously, on Day 1 of 21-day cycles. |
| Module A, Cohort 3: 1ary resistance patients | Experimental | Drug: Ezabenlimab, Drug: BI 754111Patients with select advanced or metastatic solid tumor types, who have been previously treated with previous anti-PD-1 or anti-PD-L1-based therapies without achieving benefit (stable disease for less than 6 months or progressive disease in less than 6 months), were administered 240 mg of ezabenlimab (BI 754091), intravenously, on Day 1 of 21-day cycles, along with 600 mg of BI 754111, intravenously, on Day 1 of 21-day cycles. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- Provision of signed and dated, written Master informed consent form (ICF) prior to any trial-specific procedures, sampling, or analyses.
- Patient ≥18 years of age at the time of signature of the ICF.
- Eastern Cooperative Oncology Group (ECOG) score: 0 or 1.
- Patient must agree to a pre-treatment biopsy (if archival tissue is not available) and on-treatment tumour biopsy. If archived tumour tissue is available from the last treatment failure, sections may be supplied instead of a pre-treatment biopsy.
- Life expectancy of at least 12 weeks after the start of the treatment according to the Investigator's judgement.
Key exclusion criteria (15 listed)
- Any investigational treatment anti-tumour treatment within 4 weeks or within 5 half-life periods (whichever is shorter) prior to the initiation of trial treatment.
- More than one anti-PD-(L)1-based treatment regimen prior to entering study study, more specifically defined in the modules. Note: once in a trial Module, patients may crossover to different Module if all other eligibility criteria are met.
- Major surgery ('major' according to the Investigator's assessment) performed within 12 weeks prior to first trial treatment or planned within 12 months after screening, e.g., hip replacement.
- Known history of severe hypersensitivity reactions to other mAbs or known hypersensitivity to the trial drugs or their excipients.
- Presence of central nervous system (CNS) metastases, unless treated and asymptomatic and off corticosteroids and/or anticonvulsant therapy for at least 2 weeks prior to start of treatment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EzabenlimabAlso: BI 754091240 mg of ezabenlimab (BI 754091), intravenously, on Day 1 of 21-day cycles. | Drug | Module A, Cohort 1: GEC patients, Module A, Cohort 2: 2ary resistance patients, Module A, Cohort 3: 1ary resistance patients, Module C, Cohort 1: GEC patients, Module C, Cohort 2: 2ary resistance patients, Module C, Cohort 3: 1ary resistance patients, Module C, Cohort 4: CRC patients, Module C, Cohort 5: EC patients |
| BI 754111600 mg of BI 754111, intravenously, on Day 1 of 21-day cycles. | Drug | Module A, Cohort 1: GEC patients, Module A, Cohort 2: 2ary resistance patients, Module A, Cohort 3: 1ary resistance patients |
| BI 836880720 mg of BI 836880, intravenously, on Day 1 of 21-day cycles. | Drug | Module C, Cohort 1: GEC patients, Module C, Cohort 2: 2ary resistance patients, Module C, Cohort 3: 1ary resistance patients, Module C, Cohort 4: CRC patients, Module C, Cohort 5: EC patients |
Primary outcome
[Module C] Objective Response (OR)
Time frame: From first drug administration until the earliest of disease progression, death or last evaluable tumor assessment before start of subsequent anti-cancer therapy. Up to approximately 188.3 weeks.
Confirmed objective response (OR), defined as the percentage of participants with best overall response of complete response (CR) or partial response (PR), assessed by the investigator according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1 (v1.1). Complete response (CR) was defined as the disappearance of all target lesions and partial response (PR) was defined as decrease of at least 30% in the sum of the diameter of target lesions taking the baseline sum diameters as reference.
[Module C] Objective Response (OR) - Bayesian Hierarchical Model
Time frame: From first drug administration until the earliest of disease progression, death or last evaluable tumor assessment before start of subsequent anti-cancer therapy. Up to approximately 188.3 weeks.
Confirmed objective response (OR), defined as the objective response rate (ORR) of participants with best overall response of complete response (CR) or partial response (PR), assessed by the investigator according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1 (v1.1). Complete response (CR) was defined as the disappearance of all target lesions and partial response (PR) was defined as decrease of at least 30% in the sum of the diameter of target lesions taking the baseline sum diameters as reference. The estimated objective response rate is presented by the posterior medians of the Bayesian hierarchical model and by the correspondent credible intervals.
[Module A] Objective Response (OR)
Time frame: From first drug administration until the earliest of disease progression, death or last evaluable tumor assessment before start of subsequent anti-cancer therapy. Up to approximately 152.4 weeks.
Confirmed objective response (OR), defined as the percentage of participants with best overall response of complete response (CR) or partial response (PR), assessed by the investigator according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1 (v1.1). Complete response (CR) was defined as the disappearance of all target lesions and partial response (PR) was defined as decrease of at least 30% in the sum of the diameter of target lesions taking the baseline sum diameters as reference.
[Module A] Objective Response (OR) - Bayesian Hierarchical Model
Time frame: From first drug administration until the earliest of disease progression, death or last evaluable tumor assessment before start of subsequent anti-cancer therapy. Up to approximately 152.4 weeks.
Confirmed objective response (OR), defined as the objective response rate (ORR) of participants with best overall response of complete response (CR) or partial response (PR), assessed by the investigator according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1 (v1.1). Complete response (CR) was defined as the disappearance of all target lesions and partial response (PR) was defined as decrease of at least 30% in the sum of the diameter of target lesions taking the baseline sum diameters as reference. The estimated objective response rate is presented by the posterior medians of the Bayesian hierarchical model and by the correspondent credible intervals.
8 secondary outcomes
[Module C] Duration of Response (DoR)
Time frame: From first documented CR or PR (RECIST v1.1) until the earlier of disease progression or death. Up to 174.6 weeks.
[Module C] Disease Control (DC)
Time frame: From first drug administration until the earliest of disease progression, death or last evaluable tumor assessment before start of subsequent anti-cancer therapy. Up to approximately 188.3 weeks.
[Module C] Disease Control (DC) - Bayesian Hierarchical Model
Time frame: From first drug administration until the earliest of disease progression, death or last evaluable tumor assessment before start of subsequent anti-cancer therapy. Up to approximately 188.3 weeks.
[Module C] Progression-free Survival (PFS)
Time frame: From first drug administration until PD or death, whichever occurred earlier. Up to approximately 186.1 weeks.
[Module A] Duration of Response (DoR)
Time frame: From first documented CR or PR (RECIST v1.1) until the earlier of disease progression or death. Up to 63.6 weeks.
[Module A] Disease Control (DC)
Time frame: From first drug administration until the earliest of disease progression, death or last evaluable tumor assessment before start of subsequent anti-cancer therapy. Up to approximately 152.4 weeks.
[Module A] Disease Control (DC) - Bayesian Hierarchical Model
Time frame: From first drug administration until the earliest of disease progression, death or last evaluable tumor assessment before start of subsequent anti-cancer therapy. Up to approximately 152.4 weeks.
[Module A] Progression-free Survival (PFS)
Time frame: From first drug administration until PD, death, or cut-off date of July 2021, whichever occurred earlier. Up to approximately 104.7 weeks.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: No. Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents. Exceptions might apply, e.g. studies in products where Boehringer Ingelheim is not the license holder; studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; studies conducted in a single center or targeting rare diseases(in case of low number of patients and therefore limitations with anonymization). For more details refer to: https://www.mystudywindow.com/msw/datatransparency
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
17 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ezabenlimab, BI 754111 and BI 836880 in people with Neoplasm Metastasis and Advanced Tumors, run by Boehringer Ingelheim at 17 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 23 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in United States, United Kingdom, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Jan 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
[Module C] Objective Response (OR) (time frame: From first drug administration until the earliest of disease progression, death or last evaluable tumor assessment before start of subsequent anti-cancer therapy. Up to approximately 188.3 weeks.). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jan 2026.