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

Advanced NSCLC Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04982224
• Other study ID #: R5093-M114-ONC-1864
• Secondary ID: 2020-005065-14
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: November 9, 2021
• Est. completion date: February 1, 2030

Study information

• Verified date: February 2024
• Source: Regeneron Pharmaceuticals
• Contact: Clinical Trials Administrator
• Phone: 844-734-6643
• Email: clinicaltrials[@]regeneron.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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)

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 237
• Est. completion date: February 1, 2030
• Est. primary completion date: February 1, 2030
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced NSCLC

Intervention

Drug:
• REGN5093-M114
Administered by intravenous (IV) infusion
• Cemiplimab
Administered by IV infusion

Locations

Country	Name	City	State
United States	University of Colorado Hospital - Anschutz Cancer Pavilion (ACP)	Aurora	Colorado
United States	John Hopkins	Baltimore	Maryland
United States	Johns Hopkins Satellite Site	Baltimore	Maryland
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Medical University of South Carolina (MUSC)	Charleston	South Carolina
United States	Henry Ford Hospital	Detroit	Michigan
United States	Virginia Cancer Specilaist	Fairfax	Virginia
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	University of California Irvine Medical Center (UCIMC)	Irvine	California
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	NYU Langone Medical Center	New York	New York
United States	University of Pittsburgh Medical Center - Hillman Cancer Center	Pittsburgh	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose limiting toxicities (DLTs)	Dose escalation (Phase 1)	Up to 28 days
Primary	Treatment-emergent adverse events (TEAEs)	Dose escalation (Phase 1)	Through study completion, an average of 2 years
Primary	Serious adverse events (SAEs)	Dose escalation (Phase 1)	Through study completion, an average of 2 years
Primary	TEAEs leading to study treatment discontinuation	Dose escalation (Phase 1)	Through study completion, an average of 2 years
Primary	TEAEs leading to death	Dose escalation (Phase 1)	Through study completion, an average of 2 years
Primary	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
Primary	Concentrations of REGN5093-M114 in serum	Dose escalation (Phase 1)	Through study completion, an average of 2 years
Primary	Total monoclonal antibodies (REGN5093- M114 plus unconjugated antibody) in serum	Dose escalation (Phase 1)	Through study completion, an average of 2 years
Primary	Concentrations of M24 in plasma	Dose escalation (Phase 1)	Through study completion, an average of 2 years
Primary	Concentrations of cemiplimab when given in combination with REGN5093-M114	Dose escalation (Phase 1) Cohort C	Through study completion, an average of 2 years
Primary	Objective response rate (ORR)	Dose expansion (Phase 2)	Through study completion, an average of 2 years
Secondary	ORR	Dose escalation (Phase 1)	Through study completion, an average of 2 years
Secondary	TEAEs	Dose expansion (Phase 2)	Through study completion, an average of 2 years
Secondary	SAEs	Dose expansion (Phase 2)	Through study completion, an average of 2 years
Secondary	TEAEs leading to study treatment discontinuation	Dose expansion (Phase 2)	Through study completion, an average of 2 years
Secondary	TEAEs leading to death	Dose expansion (Phase 2)	Through study completion, an average of 2 years
Secondary	Laboratory abnormalities (grade 3 or higher per CTCAE)	Dose expansion (Phase 2)	Through study completion, an average of 2 years
Secondary	Concentrations of REGN5093-M114 in serum	Dose expansion (Phase 2)	Through study completion, an average of 2 years
Secondary	Total monoclonal antibodies (REGN5093- M114 plus unconjugated antibody) in serum	Dose expansion (Phase 2)	Through study completion, an average of 2 years
Secondary	Concentrations of M24 in plasma	Dose expansion (Phase 2)	Through study completion, an average of 2 years
Secondary	Concentrations of cemiplimab when given in combination with REGN5093-M114	Dose expansion (Phase 2) Cohort C	Through study completion, an average of 2 years
Secondary	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
Secondary	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
Secondary	Duration of response (DOR)	Phase 1 and Phase 2	Through study completion, an average of 2 years
Secondary	Disease control rate (DCR)	Phase 1 and Phase 2	Through study completion, an average of 2 years
Secondary	Time to tumor response (TTR)	Phase 1 and Phase 2	Through study completion, an average of 2 years
Secondary	Progression free survival (PFS)	Phase 1 and Phase 2	Through study completion, an average of 2 years
Secondary	Overall survival (OS)	Phase 1 and Phase 2	Through study completion, an average of 2 years
Secondary	Incidence of ADA to REGN5093-M114 over time in monotherapy	Phase 1 and Phase 2	Through study completion, an average of 2 years
Secondary	Titer of ADA to REGN5093-M114 over time in monotherapy	Phase 1 and Phase 2	Through study completion, an average of 2 years
Secondary	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
Secondary	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