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

• ClinicalTrials.gov Identifier: NCT04077099
• Recruitment Status: Active, not recruiting
• First Posted: September 4, 2019
• Last Update Posted: March 10, 2023
• Sponsor: Regeneron Pharmaceuticals
• Information provided by (Responsible Party): Regeneron Pharmaceuticals

Study Description

Brief Summary:

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)

Condition or disease	Intervention/treatment	Phase
NSCLC	Drug: REGN5093	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 82 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1/2 Study of REGN5093 in Patients With MET-Altered Advanced Non-Small Cell Lung Cancer
• Actual Study Start Date: January 7, 2020
• Estimated Primary Completion Date: October 20, 2024
• Estimated Study Completion Date: October 20, 2024

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Alabama

Regeneron Research Facility

Birmingham, Alabama, United States, 35294

United States, California

Regeneron Research Facility

Orange, California, United States, 92868

United States, District of Columbia

Regeneron Research Facility

Washington, District of Columbia, United States, 20007

United States, Florida

Regeneron Research Facility

Tampa, Florida, United States, 33612

United States, Kentucky

Regeneron Research Facility

Lexington, Kentucky, United States, 40536

United States, Massachusetts

Regeneron Research Facility

Boston, Massachusetts, United States, 02215

United States, Michigan

Regeneron Research Facility

Detroit, Michigan, United States, 48202

United States, Missouri

Regeneron Research Facility

Saint Louis, Missouri, United States, 63110

United States, New York

Regeneron Research Facility

New York, New York, United States, 10016

Regeneron Research Facility

New York, New York, United States, 10029

Regeneron Research Facility

New York, New York, United States, 10065

United States, North Carolina

Regeneron Research Facility

Durham, North Carolina, United States, 27710

United States, Oklahoma

Regeneron Research Facility

Oklahoma City, Oklahoma, United States, 73104

United States, Pennsylvania

Regeneron Research Facility

Philadelphia, Pennsylvania, United States, 19111

Regeneron Research Facility

Pittsburgh, Pennsylvania, United States, 15232

United States, Texas

Regeneron Research Facility

Dallas, Texas, United States, 75390

Regeneron Research Facility

Houston, Texas, United States, 77030

France

Regeneron Research Facility

Bordeaux Cedex 9, France, 33076

Regeneron Study Site

Caen cedex, France, 14076

Regeneron Research Facility

Dijon Cedex, France, 21034

Regeneron Research Facility

Grenoble, France, 38043

Regeneron Research Facility

Montpellier, France, 34295

Regeneron Research Facility

Rennes Cedex 9, France, 35033

Korea, Republic of

Regeneron Research Facility

Gyeonggi do, Gyeonggi, Korea, Republic of, 10408

Regeneron Research Facility

Suwon, Gyeonggi, Korea, Republic of, 16247

Regeneron Research Facility

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

Sponsors and Collaborators

Regeneron Pharmaceuticals

Investigators

• Study Director: Clinical Trial Management; Regeneron Pharmaceuticals

More Information

• Responsible Party: Regeneron Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT04077099
• Other Study ID Numbers: R5093-ONC-1863; 2019-001908-38 ( EudraCT Number )
• First Posted: September 4, 2019
• Last Update Posted: March 10, 2023
• Last Verified: March 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code
• 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.
• 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).
• URL: https://vivli.org/

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Regeneron Pharmaceuticals:

MET (mesenchymal-epithelial transition factor); HGF (Hepatocyte Growth Factor); NSCLC (non-small cell lung cancer); MET-altered advanced; Unresectable; Metastatic disease

Additional relevant MeSH terms:

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms