REGN5093 in Patients With MET-Altered Advanced Non-Small Cell Lung 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 REGN5093 for determination of the maximum tolerated dose (MTD) and/or definition of the recommended phase 2 dose (RP2D) of REGN5093 in patients with MET-altered 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 as measured by the objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1)

Official Title
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A Phase 1/2 Study of REGN5093 in Patients With MET-Altered Advanced Non-Small Cell Lung Cancer

Conditions
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NSCLC

Intervention / Treatment
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* Drug: REGN5093


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Histologically confirmed NSCLC that is at advanced stage. Advanced is defined as unresectable or metastatic disease. Patients must have exhausted all approved available therapies appropriate for the patient. Has available archival tumor tissue, unless discussed with the medical monitor. Willing to provide tumor tissue from newly obtained biopsy. Newly obtained biopsies at screening are required unless medically contra-indicated and discussed with the medical monitor. For patients in expansion cohorts, biopsies should be taken from tumor site which has not been irradiated previously and is not the only measurable target lesion. Previously documented presence of MET alterations: either MET-exon14 gene mutation and/or MET gene amplification, and/or elevated MET protein expression, 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 (i.e. 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 (i.e. grade ≤1 or baseline) from AEs, except for laboratory changes as described in the protocol and patients with grade ≤2 neuropathy For expansion cohorts only: prior treatment with MET-targeted biologic therapy (function-blocking antibodies or ADCs) For expansion cohorts only (except cohort 1A) prior treatment with any MET-targeted agent including small molecule tyrosine kinase inhibitors eg, crizotinib, capmatinib, tepotinib, as defined in the protocol Untreated or active primary brain tumor, CNS metastases, leptomeningeal disease or spinal cord compression 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<br>Monotherapy in dose escalation cohorts (phase 1) followed by an expansion phase (phase 2) | Drug: REGN5093<br>* Intravenous (IV) infusion. There will be a series of dose escalation cohorts followed by an expansion phase.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with Dose Limiting Toxicities | Phase 1/Dose escalation | Up to 21 days | 
| Incidence and severity of treatment-emergent adverse events | Phase 1/Dose escalation | Through study completion, an average of 4 years | 
| Incidence and severity of adverse events of special interest (AESIs) | Phase 1/Dose escalation | Through study completion, an average of 4 years | 
| Incidence and severity of serious adverse events (SAEs) | Phase 1/Dose escalation | Through study completion, an average of 4 years | 
| Incidence and severity of grade ≥3 laboratory abnormalities | Phase 1/Dose escalation | Through study completion, an average of 4 years | 
| REGN5093 concentrations in serum over time | Phase 1/Dose escalation | Through study completion, an average of 4 years | 
| Objective response rate (ORR) per RECIST 1.1 | Phase 2/Dose expansion | Through study completion, an average of 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR per RECIST 1.1 | Phase 1/Dose escalation | Through study completion, an average of 4 years | 
| Incidence and severity of TEAEs | Phase 2/Dose expansion | Through study completion, an average of 4 years | 
| Incidence and severity of AESIs | Phase 2/Dose expansion | Through study completion, an average of 4 years | 
| Incidence and severity of SAEs | Phase 2/Dose expansion | Through study completion, an average of 4 years | 
| Incidence and severity of grade ≥3 laboratory abnormalities | Phase 2/Dose expansion | Through study completion, an average of 4 years | 
| REGN5093 Pharmacokinetics (PK) | Phase 2/Dose expansion | Through study completion, an average of 4 years | 
| REGN5093 concentrations in serum over time | Phase 2/Dose expansion | Through study completion, an average of 4 years | 
| Duration of response (DOR) per RECIST 1.1. | Phase 1 and 2 | Through study completion, an average of 4 years | 
| Disease control rate (DCR) per RECIST 1.1. | Phase 1 and 2 | Through study completion, an average of 4 years | 
| Progression free survival (PFS) per RECIST 1.1. | Phase 1 and 2 | Through study completion, an average of 4 years | 
| Overall survival (OS) | Phase 1 and 2 | Through study completion, an average of 4 years | 
| Immunogenicity as measured by Anti-drug antibodies (ADA) to REGN5093 | Phase 1 and 2 | Through study completion, an average of 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MET (mesenchymal-epithelial transition factor), HGF (Hepatocyte Growth Factor), NSCLC (non-small cell lung cancer), Unresectable, Metastatic disease, MET-altered advanced