REGN5093 in Patients With MET-Altered Advanced Non-Small Cell Lung Cancer

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

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)

Study Overview

• Status: Active, not recruiting
• Conditions: NSCLC
• Intervention / Treatment: Drug: REGN5093

• Study Type: Interventional
• Enrollment (Actual): 82
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• France
  • Bordeaux Cedex 9, France, 33076
    • Regeneron Research Facility
  • Caen cedex, France, 14076
    • Regeneron Study Site
  • Dijon Cedex, France, 21034
    • Regeneron Research Facility
  • Grenoble, France, 38043
    • Regeneron Research Facility
  • Montpellier, France, 34295
    • Regeneron Research Facility
  • Rennes Cedex 9, France, 35033
    • Regeneron Research Facility
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Regeneron Research Facility
  • Seoul, Korea, Republic of, 03722
    • Regeneron Research Facility
  • Seoul, Korea, Republic of, 05505
    • Regeneron Research Facility
  • Seoul, Korea, Republic of, 06351
    • Regeneron Research Facility
  • Seoul, Korea, Republic of, 06591
    • Regeneron Research Facility
  • Gyeonggi
    • Gyeonggi do, Gyeonggi, Korea, Republic of, 10408
      • Regeneron Research Facility
    • Suwon, Gyeonggi, Korea, Republic of, 16247
      • Regeneron Research Facility
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Regeneron Research Facility
  • California
    • Orange, California, United States, 92868
      • Regeneron Research Facility
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Regeneron Research Facility
  • Florida
    • Tampa, Florida, United States, 33612
      • Regeneron Research Facility
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • Regeneron Research Facility
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Regeneron Research Facility
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Regeneron Research Facility
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Regeneron Research Facility
  • New York
    • New York, New York, United States, 10029
      • Regeneron Research Facility
    • New York, New York, United States, 10016
      • Regeneron Research Facility
    • New York, New York, United States, 10065
      • Regeneron Research Facility
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Regeneron Research Facility
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Regeneron Research Facility
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Regeneron Research Facility
    • Pittsburgh, Pennsylvania, United States, 15232
      • Regeneron Research Facility
  • Texas
    • Dallas, Texas, United States, 75390
      • Regeneron Research Facility
    • Houston, Texas, United States, 77030
      • Regeneron Research Facility

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: REGN5093; Monotherapy in dose escalation cohorts (phase 1) followed by an expansion phase (phase 2)	Drug: REGN5093; Intravenous (IV) infusion. There will be a series of dose escalation cohorts followed by an expansion phase.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Investigators: Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): January 7, 2020
• Primary Completion (Estimated): October 20, 2024
• Study Completion (Estimated): October 20, 2024

Study Registration Dates

• First Submitted: August 13, 2019
• First Submitted That Met QC Criteria: August 29, 2019
• First Posted (Actual): September 4, 2019

Study Record Updates

• Last Update Posted (Actual): March 6, 2024
• Last Update Submitted That Met QC Criteria: March 5, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Unresectable; Metastatic disease; MET (mesenchymal-epithelial transition factor); HGF (Hepatocyte Growth Factor); NSCLC (non-small cell lung cancer); MET-altered advanced
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: R5093-ONC-1863; 2019-001908-38 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
• IPD Sharing Time Frame: Individual anonymized participant data will be considered for sharing once the indication has been approved by a regulatory body, if there is legal authority to share the data and there is not a reasonable likelihood of participant re-identification.
• IPD Sharing Access Criteria: Qualified researchers may request access to anonymized patient level data or aggregate study data when Regeneron has received marketing authorization from major health authorities (e.g., FDA, EMA, PMDA, etc) for the product and indication, has the legal authority to share the data, and has made the study results publicly available (eg, scientific publication, scientific conference, clinical trial registry).
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; 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