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About
Phase II, multicenter, open-label, multi-cohort proof-of-concept study designed to evaluate the safety and efficacy of Ezabenlimab combined with BI 907828 in patients with unresectable, locally advanced or metastatic solid tumors.
Full description
This study is a phase II, multicenter, open-label, multi-cohort proof-of-concept study designed to evaluate the safety and efficacy of Ezabenlimab combined with BI 907828 in patients with unresectable, locally advanced or metastatic solid tumors.
Inclusions will proceed independently for 2 cohorts of patients with TP53 wild-type and TLS+ tumors (TLS: tertiary lymphoid strucutres), as follows:
Cohort A: soft-tissue sarcomas
Cohort B: Solid tumors [non-small cell lung cancer (NSCLC) or triple negative breast cancer (TNBC) or MMS colorectal cancer (MSS-CCR) or biliary tract cancer (BTC)]
Sex
Ages
Volunteers
Inclusion criteria
Histologically or cytologically confirmed diagnosis:
Age ≥ 18 years,
Advanced/unresectable and/or metastatic disease,
Mature TLS positive status
TP53-wild type status known (by molecular biology)
Cohort A: MDM2 status known at the time of inclusion
Cohort B: are eligible the following populations
Patients must have measurable disease (lesion in previously irradiated filed can be considered as measurable if progressive at inclusion according to RECIST v1.1) defined as per RECIST v1.1 with at least one lesion that can be measured in at least one dimension (longest diameter to be recorded) as > 10 mm with spiral CT scan.,
Performance status 0-2
Life expectancy ≥ 8 weeks,
Adequate hematologic and end-organ function as defined per protocol
Disease progression on prior treatment, or previously untreated disease with no available acceptable treatment
Recovery to grade ≤ 1 from any adverse event (AE) derived from previous treatment (excluding alopecia and vitiligo of any grade and non-painful peripheral neuropathy grade ≤ 2) according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE, version 5.0),
Ability to comply with the study protocol, in the investigator's judgment
Female subjects of childbearing potential must have a negative serum pregnancy test within 14 days prior to the first dose of study treatment. Serum or urine pregnancy test must be repeated within 72 hours prior to receiving the first dose of study medication,
Both women of childbearing potential and men must agree to use two medically acceptable methods of contraception throughout the treatment period
No prior or concurrent malignant disease diagnosed or treated in the last 2 years except for: a. superficial/non-invasive bladder cancer, or basal or squamous cell carcinoma in situ treated with curative intent; b. endoscopically resected GI cancers limited to the mucosal layer without recurrence in > 1 year,
Voluntarily signed and dated written informed consent prior to any study specific procedure,
Patients with a social security in compliance with the French law.
Exclusion criteria
Prior treatment with ezabenlimab and/or BI 907828,
Women who are pregnant or breast feeding,
Participation to a study involving a medical or therapeutic intervention in the last 30 days,
Previous enrolment in the present study,
Patient unable to follow and comply with the study procedures because of any geographical, social or psychological reasons,
Inability to swallow,
History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins,
Known hypersensitivity to Chinese hamster ovary cell products or to any component of the ezabenlimab or BI 907828 formulation,
Symptomatic or actively progressing central nervous system (CNS) metastases.
History of leptomeningeal disease,
Primary CNS tumors with any of the following characteristics:
Any systemic anticancer treatment within 2 weeks or 5 half-lives (whichever is shorter) prior to start of ezabenlimab combined with BI 907828,
Whole brain radiotherapy within 14 days prior to start of BI 754091 combined with BI 907828
Stereotactic radiosurgery within 7 days prior to start of ezabenlimab combined with BI 907828
Active bleeding, significant risk of haemorrhage (e.g. previous severe gastrointestinal bleeding, previous haemorrhagic stroke at any time), or current bleeding disorder (e.g. haemophilia, von Willebrand disease)
History of or concurrent serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study or confounds the ability to interpret data from the study
Incomplete recovery from any surgery prior to the start of ezabenlimab combined with BI 907828 that would interfere with the determination of safety or efficacy of ezabenlimab combined with BI 907828
Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or higher), myocardial infarction, or cerebrovascular accident within 3 months prior to enrollment, unstable arrhythmias, or unstable angina
Uncontrolled tumor-related pain.
Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently).
Active or history of autoimmune disease or immune deficiency,
History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
Active tuberculosis
Severe infection within 4 weeks prior to initiation of ezabenlimab combined with BI 907828, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of ezabenlimab combined with BI 907828.
Prior allogeneic stem cell or solid organ transplantation
Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of ezabenlimab combined with BI 907828, or anticipation of need for such a vaccine during treatment or within 6 months after the final dose ezabenlimab combined with BI 907828. Seasonal flu vaccines that do not contain a live virus are permitted,
Current treatment with anti-viral therapy for HBV
Treatment with systemic immunostimulatory agents within 4 weeks or 5 drug elimination half-lives (whichever is longer) prior to initiation of ezabenlimab combined with BI 907828
Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of ezabenlimab combined with BI 907828, or anticipation of need for systemic immunosuppressive medication during ezabenlimab combined with BI 907828.
Patients with oral anticoagulation based on Vitamin K antagonist.
Primary purpose
Allocation
Interventional model
Masking
0 participants in 2 patient groups
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Central trial contact
Antoine ITALIANO, MD, PhD; Simone MATHOULIN PELISSIER, MD, PhD
Data sourced from clinicaltrials.gov
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