Study of REGN5093-M114 (METxMET Antibody-Drug Conjugate) in Adult Patients With Mesenchymal Epithelial Transition Factor (MET) Overexpressing Advanced Cancer

Study Overview
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Brief Summary
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The primary objective of the dose escalation (phase 1) part of the study is: • To assess the safety, tolerability and pharmacokinetics (PK) of the antibody drug conjugate (ADC) REGN5093-M114 in order to determine a maximum tolerated dose (MTD) and/or define the recommended phase 2 dose (RP2D) of REGN5093-M114 in patients with mesenchymal epithelial transition factor (MET) overexpressing non-small cell lung cancer (NSCLC). The primary objective of the dose expansion (phase 2) part of the study is: • To assess preliminary anti-tumor activity of REGN5093-M114 in MET-overexpressed NSCLC as measured by the objective response rate (ORR) The secondary objective of the dose escalation (phase 1) part of the study is: • To assess preliminary anti-tumor activity of REGN5093-M114 as measured by the ORR The secondary objective of the dose expansion (phase 2) part of the study is: • To assess the safety, tolerability profile, and PK of REGN5093-M114 ADC and total antibody in each expansion cohort The secondary objectives of both phases of the study are: To evaluate other measures of preliminary anti-tumor activity To assess immunogenicity to REGN5093-M114

Official Title
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A Phase 1/2 Study of REGN5093-M114 (METxMET Antibody-Drug Conjugate) in Patients With MET Overexpressing Advanced Cancer

Conditions
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Advanced NSCLC

Intervention / Treatment
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* Drug: REGN5093-M114


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Histologically confirmed NSCLC that is at advanced stage for which there are no approved therapies available expected to confer clinical benefit as defined in the protocol Willing to provide tumor tissue from newly obtained biopsy from tumor site. Newly obtained biopsies at tissue screening are required. An archival sample can be accepted only after discussion with the medical monitor and if the sample is not more than 6 months old and obtained after completion of the last therapy. The enrollment of patients will be based on an immunohistochemistry (IHC)-based assay using freshly obtained tumor biopsies or an archival biopsy as described above. Only patients with MET overexpressing tumors by central IHC analysis will be enrolled. For expansion cohorts only: tumor site for biopsy must not have been irradiated previously and must not be the only measurable lesion. Tumor must overexpress MET protein as defined in the protocol by central IHC analysis For expansion only: At least one lesion that is measurable by RECIST 1.1. Tumor lesions in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions after radiation. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Adequate organ and bone marrow function as defined in the protocol Key Exclusion Criteria: Has received treatment with an approved systemic therapy or has participated in any study of an investigational agent or investigational device within 2 weeks or 5 half-lives of the prior treatment, whichever is shorter with a minimum of 7 days from the first dose of study therapy Has not yet recovered (ie, grade ≤1 or baseline) from any acute toxicities resulting from prior therapy except as described in the protocol Has received radiation therapy or major surgery within 14 days of first administration of study drug or has not recovered from adverse events as defined in the protocol Another malignancy that is progressing or requires active treatment except as noted in the protocol Untreated or active primary brain tumor, central nervous system (CNS) metastases, leptomeningeal disease, or spinal cord compression as defined in the protocol Encephalitis, meningitis, organic brain disease (eg Parkinson's disease) or uncontrolled seizures in the year prior to first dose of study therapy Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C infection; or diagnosis of immunodeficiency as defined in the protocol NOTE: Other protocol-defined Inclusion/ Exclusion criteria apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: REGN5093-M114<br> | Drug: REGN5093-M114<br>* Administered by intravenous (IV) infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose limiting toxicities (DLTs) | Dose escalation (Phase 1) | Up to 28 days | 
| Treatment-emergent adverse events (TEAEs) | Dose escalation (Phase 1) | Through study completion, an average of 2 years | 
| Serious adverse events (SAEs) | Dose escalation (Phase 1) | Through study completion, an average of 2 years | 
| Deaths | Dose escalation (Phase 1) | Through study completion, an average of 2 years | 
| Laboratory abnormalities (grade 3 or higher per Common Terminology Criteria for Adverse Events [CTCAE]) | Dose escalation (Phase 1) | Through study completion, an average of 2 years | 
| Concentrations of REGN5093-M114 in serum | Dose escalation (Phase 1) | Through study completion, an average of 2 years | 
| Total monoclonal antibodies (REGN5093- M114 plus unconjugated antibody) in serum | Dose escalation (Phase 1) | Through study completion, an average of 2 years | 
| Concentrations of M24 in plasma | Dose escalation (Phase 1) | Through study completion, an average of 2 years | 
| Objective response rate (ORR) | Dose expansion (Phase 2) | Through study completion, an average of 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR | Dose escalation (Phase 1) | Through study completion, an average of 2 years | 
| TEAEs | Dose expansion (Phase 2) | Through study completion, an average of 2 years | 
| SAEs | Dose expansion (Phase 2) | Through study completion, an average of 2 years | 
| Deaths | Dose expansion (Phase 2) | Through study completion, an average of 2 years | 
| Laboratory abnormalities (grade 3 or higher per CTCAE) | Dose expansion (Phase 2) | Through study completion, an average of 2 years | 
| Concentrations of REGN5093-M114 in serum | Dose expansion (Phase 2) | Through study completion, an average of 2 years | 
| Total monoclonal antibodies (REGN5093- M114 plus unconjugated antibody) in serum | Dose expansion (Phase 2) | Through study completion, an average of 2 years | 
| Concentrations of M24 in plasma | Dose expansion (Phase 2) | Through study completion, an average of 2 years | 
| Duration of response (DOR) | Phase 1 and Phase 2 | Through study completion, an average of 2 years | 
| Disease control rate (DCR) | Phase 1 and Phase 2 | Through study completion, an average of 2 years | 
| Time to tumor response (TTR) | Phase 1 and Phase 2 | Through study completion, an average of 2 years | 
| Progression free survival (PFS) | Phase 1 and Phase 2 | Through study completion, an average of 2 years | 
| Overall survival (OS) | Phase 1 and Phase 2 | Through study completion, an average of 2 years | 
| Immunogenicity as measured by anti-drug antibody (ADA) to REGN5093-M114 | Phase 1 and Phase 2 | Through study completion, an average of 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-small cell lung cancer, Mesenchymal epithelial transition factor (MET), MET Overexpressing Advanced Cancer