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

NCT03697304 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 1381-00092018-002344-81
• Study Type: interventional
• Target: 211
• Locations: 3 countries
• Sites: 17

Brief 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. 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.

Conditions

Metastatic Solid Tumors; Neoplasm Metastasis; Advanced Tumors

Outcome Measures

Primary Outcomes (4)

• [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.

  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.

  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.

  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.

  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)

  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)

  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

  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)

  From first drug administration until PD or death, whichever occurred earlier. Up to approximately 186.1 weeks.

• [Module A] Duration of Response (DoR)

  From first documented CR or PR (RECIST v1.1) until the earlier of disease progression or death. Up to 63.6 weeks.

Study Arms (8)

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.

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.

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.

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.

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.

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.

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.

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.

Drug: Ezabenlimab; Drug: BI 754111

Interventions

Ezabenlimab DRUG

240 mg of ezabenlimab (BI 754091), intravenously, on Day 1 of 21-day cycles.

Also known as: BI 754091

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 754111 DRUG

600 mg of BI 754111, intravenously, on Day 1 of 21-day cycles.

Module A, Cohort 1: GEC patients; Module A, Cohort 2: 2ary resistance patients; Module A, Cohort 3: 1ary resistance patients

BI 836880 DRUG

720 mg of BI 836880, intravenously, on Day 1 of 21-day cycles.

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

Eligibility Criteria

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

You may qualify if:

• 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.
• 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:

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (17)

University of California San Diego

La Jolla, California, 92093, United States

Location

Florida Cancer Specialists-Fort Myers-52980

Fort Myers, Florida, 33901, United States

Location

Florida Cancer Specialists-Saint Petersburg-52979

St. Petersburg, Florida, 33705, United States

Location

Florida Cancer Specialists-Sarasota-61670

Tallahassee, Florida, 32308, United States

Location

Florida Cancer Specialists - East

West Palm Beach, Florida, 33401, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

Norton Cancer Institute

Louisville, Kentucky, 40202, United States

Location

Oklahoma University School of Community Medicine

Oklahoma City, Oklahoma, 73104, United States

Location

Tennessee Oncology

Chattanooga, Tennessee, 37404, United States

Location

Tennessee Oncology, PLLC-Nashville-52568

Nashville, Tennessee, 37203, United States

Location

Medical College Of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Cross Cancer Institute (University of Alberta)

Edmonton, Alberta, T6G 1Z2, Canada

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 1Z6, Canada

Location

Beatson West of Scotland Cancer Centre

Glasgow, G12 0YN, United Kingdom

Location

University College Hospital

London, NW1 2BU, United Kingdom

Location

Guy's Hospital

London, SE1 9RT, United Kingdom

Location

Sarah Cannon Research Institute, London

London, W1G 6AD, United Kingdom

Location

Related Links

• Related Info

MeSH Terms

Conditions

Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

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

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 2, 2018
• First Posted: October 5, 2018
• Study Start: March 19, 2019
• Primary Completion: December 3, 2024
• Study Completion: December 3, 2024
• Last Updated: January 27, 2026
• Results First Posted: January 27, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

GB (4); CA (2); US (11)