Platform Trial Evaluating Safety and Efficacy of BI 754091 Anti- PD-1 Based Combination Therapies in PD-(L)1 naïve and PD- (L)1 Pretreated Patient Populations With Advanced/Metastatic Solid Tumours

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Neoplasm Metastasis
• Intervention / Treatment: Drug: BI 754091; Drug: BI 754111; Drug: BI 836880

• Study Type: Interventional
• Enrollment (Actual): 212
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute (University of Alberta)
  • Ontario
    • Toronto, Ontario, Canada, M5G 1Z6
      • Princess Margaret Cancer Centre
• United Kingdom
  • Glasgow, United Kingdom, G12 0YN
    • Beatson West of Scotland Cancer Centre
  • London, United Kingdom, SE1 9RT
    • Guy's Hospital
  • London, United Kingdom, W1G 6AD
    • Sarah Cannon Research Institute
  • London, United Kingdom, NW1 2BU
    • University College Hospital
• United States
  • California
    • La Jolla, California, United States, 92093
      • University of California San Diego
  • Florida
    • Fort Myers, Florida, United States, 33901
      • Florida Cancer Specialists
    • Saint Petersburg, Florida, United States, 33705
      • Florida Cancer Specialists
    • Tallahassee, Florida, United States, 32308
      • Florida Cancer Specialists
    • West Palm Beach, Florida, United States, 33401
      • Florida Cancer Specialists - East
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Norton Cancer Institute
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Oklahoma University School of Community Medicine
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Tennessee Oncology
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology, PLLC
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College Of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.
• 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.

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
• 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 a 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1 - Module A	Drug: BI 754091; Solution for infusion; Other Names: ezabenlimab; Drug: BI 754111; Solution for infusion
Experimental: Cohort 2 - Module A	Drug: BI 754091; Solution for infusion; Other Names: ezabenlimab; Drug: BI 754111; Solution for infusion
Experimental: Cohort 3 - Module A	Drug: BI 754091; Solution for infusion; Other Names: ezabenlimab; Drug: BI 754111; Solution for infusion
Experimental: Cohort 1 - Module C	Drug: BI 754091; Solution for infusion; Other Names: ezabenlimab; Drug: BI 836880; Solution for infusion
Experimental: Cohort 2 - Module C	Drug: BI 754091; Solution for infusion; Other Names: ezabenlimab; Drug: BI 836880; Solution for infusion
Experimental: Cohort 3 - Module C	Drug: BI 754091; Solution for infusion; Other Names: ezabenlimab; Drug: BI 836880; Solution for infusion
Experimental: Cohort 4 - Module C	Drug: BI 754091; Solution for infusion; Other Names: ezabenlimab; Drug: BI 836880; Solution for infusion
Experimental: Cohort 5 - Module C	Drug: BI 754091; Solution for infusion; Other Names: ezabenlimab; Drug: BI 836880; Solution for infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The primary endpoint of the trial is objective response (OR), defined as best overall response of complete response (CR) or partial response (PR) according to RECIST v1.1 as assessed by the Investigator	Up to 32 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Duration of response (DoR), defined as the time from first documented CR or PR (RECIST v1.1) until the earlier of disease progression or death among patients with OR	Up to 32 months
Disease control (DC), defined as best overall response of CR, PR, or stable disease (SD) according to RECIST v1.1 as assessed by the Investigator	Up to 32 months
Progression-free survival (PFS), defined as the time from first treatment until PD or death from any cause, whichever occurs earlier	Up to 32 months

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): February 12, 2019
• Primary Completion (Estimated): June 28, 2024
• Study Completion (Estimated): June 28, 2024

Study Registration Dates

• First Submitted: October 2, 2018
• First Submitted That Met QC Criteria: October 4, 2018
• First Posted (Actual): October 5, 2018

Study Record Updates

• Last Update Posted (Estimated): September 6, 2023
• Last Update Submitted That Met QC Criteria: September 4, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Neoplasm Metastasis
• Other Study ID Numbers: 1381-0009; 2018-002344-81 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: After the study is completed and the primary manuscript is accepted for publishing, researchers can use this following link https://www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement". Also, Researchers can use the following link https://www.mystudywindow.com/msw/datasharing to find information in order to request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website. The data shared are the raw clinical study data sets.
• IPD Sharing Time Frame: After all regulatory activities are completed in the US and EU for the product and indication, and after the primary manuscript has been accepted for publication.
• IPD Sharing Access Criteria: For study documents - upon signing of a 'Document Sharing Agreement'. For study data - 1. after the submission and approval of the research proposal (checks will be performed by both the independent review panel and the sponsor, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a 'Data Sharing Agreement'.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No