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

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

This study is researching an experimental drug called REGN5093-M114 by itself and in combination with cemiplimab. The study is focused on advanced non-small cell lung cancer (NSCLC) that produces too much of a protein called mesenchymal epithelial transition factor (MET) on the cancer cell surface. The aim of the study is to see how safe, tolerable, and effective the study drug is. This study will include 3 study groups, or cohorts, and each group is split into 2 parts:

Part 1: The main purpose of part 1 is to determine a safe dose of REGN5093-M114 (Cohorts A and B), and in combination with cemiplimab (Cohort C).

Part 2: The main purpose of part 2 is to use the REGN5093-M114 dose found for each cohort in part 1 to see how well the study drug works to shrink tumors.

The study is looking at several other research questions, including:

• What side effects may happen from receiving the study drug
• Does the study drug work to reduce or delay the progression of your cancer
• How much study drug is in the blood at different times
• Does the body make antibodies against the study drug (which could make the drug less effective or could lead to side effects)

Study Overview

• Status: Terminated
• Conditions: Advanced NSCLC
• Intervention / Treatment: Drug: Cemiplimab; Drug: REGN5093-M114

Detailed Description

The trial was intended to be a Phase 1/2 trial, but no participants were enrolled in Phase 2

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Orange, California, United States, 92868
      • University of California Irvine School of Medicine - Suite 400, Room 407
  • Colorado
    • Denver, Colorado, United States, 80045
      • University of Colorado Hospital Anshutz Outpatient Pavillion
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Johns Hopkins Hospital - Clinical Study Location - Skip Viragh Outpatient Cancer Building
    • Baltimore, Maryland, United States, 21231
      • Sidney Kimmel Comprehensive Cancer Center - 4F Second Medical Building
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital, Henry Ford Cancer Institute
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Medical Center - Hillman Cancer Center
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • MUSC Hollings Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • NEXT Virginia

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria:

1. 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
2. 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 was obtained on the treatment regimen prior to study screening or 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.
3. Tumor must overexpress MET protein as defined in the protocol
4. 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.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
6. Adequate organ and bone marrow function as defined in the protocol

Key Exclusion Criteria:

1. 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
2. Has not yet recovered (ie, grade ≤1 or baseline) from any acute toxicities resulting from prior therapy except as described in the protocol
3. 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
4. Another malignancy that is progressing or requires active treatment except as noted in the protocol
5. Untreated or active primary brain tumor, central nervous system (CNS) metastases, leptomeningeal disease, or spinal cord compression as defined in the protocol
6. Encephalitis, meningitis, organic brain disease (eg Parkinson's disease) or uncontrolled seizures in the year prior to first dose of study therapy
7. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1. Dose Escalation; Cohorts A and B: REGN5093-M114 monotherapy. Cohort C: REGN5093-M114+cemiplimab combination.	Drug: Cemiplimab; Administered by IV infusion; Drug: REGN5093-M114; Administered by intravenous (IV) infusion
Experimental: Phase 2. Dose Expansion; Cohorts A and B: REGN5093-M114 monotherapy. Cohort C: REGN5093-M114+cemiplimab combination.	Drug: Cemiplimab; Administered by IV infusion; Drug: REGN5093-M114; Administered by intravenous (IV) infusion

What is the study measuring?

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
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
TEAEs leading to study treatment discontinuation	Dose escalation (Phase 1)	Through study completion, an average of 2 years
TEAEs leading to death	Dose escalation (Phase 1)	Through study completion, an average of 2 years
Concentrations of cemiplimab when given in combination with REGN5093-M114	Dose escalation (Phase 1) Cohort C	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
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
TEAEs leading to study treatment discontinuation	Dose expansion (Phase 2)	Through study completion, an average of 2 years
TEAEs leading to death	Dose expansion (Phase 2)	Through study completion, an average of 2 years
Concentrations of cemiplimab when given in combination with REGN5093-M114	Dose expansion (Phase 2) Cohort C	Through study completion, an average of 2 years
Incidence of Anti-drug antibodies (ADA) against cemiplimab over time, when given in combination with REGN5093-M114	Dose expansion (Phase 2) Cohort C	Through study completion, an average of 2 years
Titer of ADA against cemiplimab over time, when given in combination with REGN5093-M114	Dose expansion (Phase 2) Cohort C	Through study completion, an average of 2 years
Incidence of ADA to REGN5093-M114 over time in monotherapy	Phase 1 and Phase 2	Through study completion, an average of 2 years
Titer of ADA to REGN5093-M114 over time in monotherapy	Phase 1 and Phase 2	Through study completion, an average of 2 years
Incidence of ADA to REGN5093-M114 over time in combination with cemiplimab	Phase 1 and Phase 2	Through study completion, an average of 2 years
Titer of ADA to REGN5093-M114 over time in combination with cemiplimab	Phase 1 and Phase 2	Through study completion, an average of 2 years

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): November 9, 2021
• Primary Completion (Actual): October 15, 2025
• Study Completion (Actual): October 15, 2025

Study Registration Dates

• First Submitted: July 20, 2021
• First Submitted That Met QC Criteria: July 20, 2021
• First Posted (Actual): July 29, 2021

Study Record Updates

• Last Update Posted (Estimated): November 3, 2025
• Last Update Submitted That Met QC Criteria: October 30, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Non-small cell lung cancer; Mesenchymal epithelial transition factor (MET); MET Overexpressing Advanced Cancer
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Antineoplastic Agents, Immunological; Antineoplastic Agents; cemiplimab
• Other Study ID Numbers: R5093-M114-ONC-1864; 2020-005065-14 (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

When Regeneron has:

• received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication or has globally discontinued development of the product for all indications on or after April 2020 and has no plans for future development
• made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry)
• the legal authority to share the data, and
• ensured the ability to protect participant privacy.

• IPD Sharing Access Criteria: Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf
• 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