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.

Sponsor
Boehringer Ingelheim (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT03697304
Collaborator
(none)
212
17
8
50.8
12.5
0.2

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: BI 754091
  • Drug: BI 754111
  • Drug: BI 836880
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
212 participants
Allocation:
Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open-label, Phase II, Platform Trial Evaluating Safety and Efficacy of Multiple BI 754091 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
Actual Study Start Date :
Mar 7, 2019
Anticipated Primary Completion Date :
May 31, 2023
Anticipated Study Completion Date :
May 31, 2023

Arms and Interventions

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

    Outcome Measures

    Primary Outcome Measures

    1. 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

    1. 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]

    2. 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]

    3. 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]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of California San Diego La Jolla California United States 92093
    2 Florida Cancer Specialists Fort Myers Florida United States 33901
    3 Florida Cancer Specialists Saint Petersburg Florida United States 33705
    4 Florida Cancer Specialists Tallahassee Florida United States 32308
    5 Florida Cancer Specialists - East West Palm Beach Florida United States 33401
    6 Indiana University Indianapolis Indiana United States 46202
    7 Norton Cancer Institute Louisville Kentucky United States 40202
    8 Oklahoma University School of Community Medicine Oklahoma City Oklahoma United States 73104
    9 Tennessee Oncology Chattanooga Tennessee United States 37404
    10 Tennessee Oncology, PLLC Nashville Tennessee United States 37203
    11 Medical College Of Wisconsin Milwaukee Wisconsin United States 53226
    12 Cross Cancer Institute (University of Alberta) Edmonton Alberta Canada T6G 1Z2
    13 Princess Margaret Cancer Centre Toronto Ontario Canada M5G 1Z5
    14 Beatson West of Scotland Cancer Centre Glasgow United Kingdom G12 0YN
    15 University College Hospital London United Kingdom NW1 2BU
    16 Guy's Hospital London United Kingdom SE1 9RT
    17 Sarah Cannon Research Institute London United Kingdom W1G 6AD

    Sponsors and Collaborators

    • Boehringer Ingelheim

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Boehringer Ingelheim
    ClinicalTrials.gov Identifier:
    NCT03697304
    Other Study ID Numbers:
    • 1381-0009
    • 2018-002344-81
    First Posted:
    Oct 5, 2018
    Last Update Posted:
    Aug 10, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Aug 10, 2022