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Completed

NCT Number: NCT03697304

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

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.

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Key information

Conditions

Neoplasm Metastasis Advanced Tumors Metastatic Solid Tumors Neoplasms Neoplastic Processes Pathologic Processes Pathological Conditions, Signs and Symptoms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Cross Cancer Institute (University of Alberta), Edmonton, Alberta, Canada

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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:

  • 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

Exclusion criteria

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
  • Known inherited predisposition to bleeding or to thrombosis, in the opinion of the investigator - Further exclusion criteria apply

Treatment and study plan

Ezabenlimab

Drug

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

Other names: BI 754091

BI 754111

Drug

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

BI 836880

Drug

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

Primary outcomes

  1. [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.

  2. [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.

  3. [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.

  4. [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.

Secondary outcomes

  1. [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.

    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.

  2. [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.

    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.

  3. [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.

    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.

  4. [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.

    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.

  5. [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.

    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.

  6. [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.

    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.

  7. [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.

    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.

  8. [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.

    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.

Sponsors and collaborators

Lead sponsor

Boehringer Ingelheim

Industry

Registry information

Official study 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

Important dates

Study start
2019
Primary completion
2024
Study completion
2024
First posted
Oct 5, 2018
Registry last updated
Jan 27, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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