Clinical trial NCT04982224: Study of REGN5093-M114 (METxMET Antibody-Drug Conjugate) in Adult Patients With Mesenchymal Epithelial Transition Factor (MET) Overexpressing Advanced Cancer
Official title: A Phase 1/2 Study of REGN5093-M114 (METxMET Antibody-Drug Conjugate) in Patients With MET Overexpressing Advanced Cancer
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Advanced NSCLC
Keywords: Non-small cell lung cancer
Mesenchymal epithelial transition factor (MET)
MET Overexpressing Advanced Cancer
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2021-07-29
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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)


Eligibility criteria: 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

Primary outcomes:
measure: Dose limiting toxicities (DLTs)
timeFrame: Up to 28 days
measure: Treatment-emergent adverse events (TEAEs)
timeFrame: Through study completion, an average of 2 years
measure: Serious adverse events (SAEs)
timeFrame: Through study completion, an average of 2 years
measure: TEAEs leading to study treatment discontinuation
timeFrame: Through study completion, an average of 2 years
measure: TEAEs leading to death
timeFrame: Through study completion, an average of 2 years
measure: Laboratory abnormalities (grade 3 or higher per Common Terminology Criteria for Adverse Events [CTCAE])
timeFrame: Through study completion, an average of 2 years
measure: Concentrations of REGN5093-M114 in serum
timeFrame: Through study completion, an average of 2 years
measure: Total monoclonal antibodies (REGN5093- M114 plus unconjugated antibody) in serum
timeFrame: Through study completion, an average of 2 years
measure: Concentrations of M24 in plasma
timeFrame: Through study completion, an average of 2 years
measure: Concentrations of cemiplimab when given in combination with REGN5093-M114
timeFrame: Through study completion, an average of 2 years
measure: Objective response rate (ORR)
timeFrame: Through study completion, an average of 2 years
Secondary outcomes:
measure: ORR
timeFrame: Through study completion, an average of 2 years
measure: TEAEs
timeFrame: Through study completion, an average of 2 years
measure: SAEs
timeFrame: Through study completion, an average of 2 years
measure: TEAEs leading to study treatment discontinuation
timeFrame: Through study completion, an average of 2 years
measure: TEAEs leading to death
timeFrame: Through study completion, an average of 2 years
measure: Laboratory abnormalities (grade 3 or higher per CTCAE)
timeFrame: Through study completion, an average of 2 years
measure: Concentrations of REGN5093-M114 in serum
timeFrame: Through study completion, an average of 2 years
measure: Total monoclonal antibodies (REGN5093- M114 plus unconjugated antibody) in serum
timeFrame: Through study completion, an average of 2 years
measure: Concentrations of M24 in plasma
timeFrame: Through study completion, an average of 2 years
measure: Concentrations of cemiplimab when given in combination with REGN5093-M114
timeFrame: Through study completion, an average of 2 years
measure: Incidence of Anti-drug antibodies (ADA) against cemiplimab over time, when given in combination with REGN5093-M114
timeFrame: Through study completion, an average of 2 years
measure: Titer of ADA against cemiplimab over time, when given in combination with REGN5093-M114
timeFrame: Through study completion, an average of 2 years
measure: Duration of response (DOR)
timeFrame: Through study completion, an average of 2 years
measure: Disease control rate (DCR)
timeFrame: Through study completion, an average of 2 years
measure: Time to tumor response (TTR)
timeFrame: Through study completion, an average of 2 years
measure: Progression free survival (PFS)
timeFrame: Through study completion, an average of 2 years
measure: Overall survival (OS)
timeFrame: Through study completion, an average of 2 years
measure: Incidence of ADA to REGN5093-M114 over time in monotherapy
timeFrame: Through study completion, an average of 2 years
measure: Titer of ADA to REGN5093-M114 over time in monotherapy
timeFrame: Through study completion, an average of 2 years
measure: Incidence of ADA to REGN5093-M114 over time in combination with cemiplimab
timeFrame: Through study completion, an average of 2 years
measure: Titer of ADA to REGN5093-M114 over time in combination with cemiplimab
timeFrame: Through study completion, an average of 2 years
Other outcomes:
Locations:
city: Orange
country: United States
facility: University of California Irvine School of Medicine - Suite 400, Room 407
state: California
city: Denver
country: United States
facility: University of Colorado Hospital Anshutz Outpatient Pavillion
state: Colorado
city: Baltimore
country: United States
facility: Johns Hopkins Hospital - Clinical Study Location - Skip Viragh Outpatient Cancer Building
state: Maryland
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center - 4F Second Medical Building
state: Maryland
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital, Henry Ford Cancer Institute
state: Michigan
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center - Hillman Cancer Center
state: Pennsylvania
city: Charleston
country: United States
facility: MUSC Hollings Cancer Center
state: South Carolina
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Fairfax
country: United States
facility: Next Virginia
state: Virginia
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: