Study of REGN5093-M114 (METxMET Antibody-Drug Conjugate) in Adult Patients With Mesenchymal Epithelial Transition Factor (MET) Overexpressing Advanced Cancer
- Registration Number
- NCT04982224
- Lead Sponsor
- Regeneron Pharmaceuticals
- Brief 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)
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 237
- 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
- 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.
- Tumor must overexpress MET protein as defined in the protocol
- 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.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Adequate organ and bone marrow function as defined in the protocol
Key
- 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 (ie, 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 from adverse events as defined in the protocol
- Another malignancy that is progressing or requires active treatment except as noted in the protocol
- Untreated or active primary brain tumor, central nervous system (CNS) metastases, leptomeningeal disease, or spinal cord compression as defined in the protocol
- Encephalitis, meningitis, organic brain disease (eg Parkinson's disease) or uncontrolled seizures in the year prior to first dose of study therapy
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Phase 1. Dose Escalation REGN5093-M114 Cohorts A and B: REGN5093-M114 monotherapy. Cohort C: REGN5093-M114+cemiplimab combination. Phase 2. Dose Expansion REGN5093-M114 Cohorts A and B: REGN5093-M114 monotherapy. Cohort C: REGN5093-M114+cemiplimab combination. Phase 1. Dose Escalation Cemiplimab Cohorts A and B: REGN5093-M114 monotherapy. Cohort C: REGN5093-M114+cemiplimab combination. Phase 2. Dose Expansion Cemiplimab Cohorts A and B: REGN5093-M114 monotherapy. Cohort C: REGN5093-M114+cemiplimab combination.
- Primary Outcome Measures
Name Time Method Concentrations of M24 in plasma Through study completion, an average of 2 years Dose escalation (Phase 1)
Objective response rate (ORR) Through study completion, an average of 2 years Dose expansion (Phase 2)
Treatment-emergent adverse events (TEAEs) Through study completion, an average of 2 years Dose escalation (Phase 1)
TEAEs leading to study treatment discontinuation Through study completion, an average of 2 years Dose escalation (Phase 1)
TEAEs leading to death Through study completion, an average of 2 years Dose escalation (Phase 1)
Laboratory abnormalities (grade 3 or higher per Common Terminology Criteria for Adverse Events [CTCAE]) Through study completion, an average of 2 years Dose escalation (Phase 1)
Concentrations of REGN5093-M114 in serum Through study completion, an average of 2 years Dose escalation (Phase 1)
Concentrations of cemiplimab when given in combination with REGN5093-M114 Through study completion, an average of 2 years Dose escalation (Phase 1) Cohort C
Dose limiting toxicities (DLTs) Up to 28 days Dose escalation (Phase 1)
Total monoclonal antibodies (REGN5093- M114 plus unconjugated antibody) in serum Through study completion, an average of 2 years Dose escalation (Phase 1)
Serious adverse events (SAEs) Through study completion, an average of 2 years Dose escalation (Phase 1)
- Secondary Outcome Measures
Name Time Method SAEs Through study completion, an average of 2 years Dose expansion (Phase 2)
Laboratory abnormalities (grade 3 or higher per CTCAE) Through study completion, an average of 2 years Dose expansion (Phase 2)
Time to tumor response (TTR) Through study completion, an average of 2 years Phase 1 and Phase 2
Overall survival (OS) Through study completion, an average of 2 years Phase 1 and Phase 2
TEAEs leading to death Through study completion, an average of 2 years Dose expansion (Phase 2)
ORR Through study completion, an average of 2 years Dose escalation (Phase 1)
TEAEs leading to study treatment discontinuation Through study completion, an average of 2 years Dose expansion (Phase 2)
Total monoclonal antibodies (REGN5093- M114 plus unconjugated antibody) in serum Through study completion, an average of 2 years Dose expansion (Phase 2)
Incidence of ADA to REGN5093-M114 over time in monotherapy Through study completion, an average of 2 years Phase 1 and Phase 2
Titer of ADA to REGN5093-M114 over time in monotherapy Through study completion, an average of 2 years Phase 1 and Phase 2
Incidence of ADA to REGN5093-M114 over time in combination with cemiplimab Through study completion, an average of 2 years Phase 1 and Phase 2
TEAEs Through study completion, an average of 2 years Dose expansion (Phase 2)
Concentrations of REGN5093-M114 in serum Through study completion, an average of 2 years Dose expansion (Phase 2)
Concentrations of M24 in plasma Through study completion, an average of 2 years Dose expansion (Phase 2)
Concentrations of cemiplimab when given in combination with REGN5093-M114 Through study completion, an average of 2 years Dose expansion (Phase 2) Cohort C
Incidence of Anti-drug antibodies (ADA) against cemiplimab over time, when given in combination with REGN5093-M114 Through study completion, an average of 2 years Dose expansion (Phase 2) Cohort C
Titer of ADA against cemiplimab over time, when given in combination with REGN5093-M114 Through study completion, an average of 2 years Dose expansion (Phase 2) Cohort C
Progression free survival (PFS) Through study completion, an average of 2 years Phase 1 and Phase 2
Duration of response (DOR) Through study completion, an average of 2 years Phase 1 and Phase 2
Disease control rate (DCR) Through study completion, an average of 2 years Phase 1 and Phase 2
Titer of ADA to REGN5093-M114 over time in combination with cemiplimab Through study completion, an average of 2 years Phase 1 and Phase 2
Trial Locations
- Locations (12)
University of California Irvine School of Medicine - Suite 400, Room 407
🇺🇸Orange, California, United States
University of Colorado Hospital Anshutz Outpatient Pavillion
🇺🇸Denver, Colorado, United States
Johns Hopkins Hospital - Clinical Study Location - Skip Viragh Outpatient Cancer Building
🇺🇸Baltimore, Maryland, United States
Sidney Kimmel Comprehensive Cancer Center - 4F Second Medical Building
🇺🇸Baltimore, Maryland, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Henry Ford Hospital, Henry Ford Cancer Institute
🇺🇸Detroit, Michigan, United States
Langone Medical Center
🇺🇸New York, New York, United States
MUSC Hollings Cancer Center
🇺🇸Charleston, South Carolina, United States
Next Virginia
🇺🇸Fairfax, Virginia, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
University of Pittsburgh Medical Center - Hillman Cancer Center
🇺🇸Pittsburgh, Pennsylvania, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States