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 6, 2024
• Sponsor: Regeneron Pharmaceuticals
• Information provided by (Responsible Party): Regeneron Pharmaceuticals

Tracking Information

• First Submitted Date: August 13, 2019
• First Posted Date: September 4, 2019
• Last Update Posted Date: March 6, 2024
• Actual Study Start Date: January 7, 2020
• Estimated Primary Completion Date: October 20, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 7, 2021)

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

Original Primary Outcome Measures (submitted: August 29, 2019)

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

Current Secondary Outcome Measures (submitted: January 7, 2021)

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

Original Secondary Outcome Measures (submitted: August 29, 2019)

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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: REGN5093 in Patients With MET-Altered Advanced Non-Small Cell Lung Cancer
• Official Title: A Phase 1/2 Study of REGN5093 in Patients With MET-Altered Advanced Non-Small Cell Lung Cancer

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)

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: NSCLC

Intervention

Drug: REGN5093

Intravenous (IV) infusion. There will be a series of dose escalation cohorts followed by an expansion phase.

Study Arms

Experimental: REGN5093

Monotherapy in dose escalation cohorts (phase 1) followed by an expansion phase (phase 2)

Intervention: Drug: REGN5093

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: March 8, 2023): 82
• Original Estimated Enrollment (submitted: August 29, 2019): 102
• Estimated Study Completion Date: October 20, 2024
• Estimated Primary Completion Date: October 20, 2024 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France, Korea, Republic of, United States

Administrative Information

• NCT Number: NCT04077099
• Other Study ID Numbers: R5093-ONC-1863; 2019-001908-38 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

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

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
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Clinical Study Report (CSR)
• Supporting Materials: 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/

• Current Responsible Party: Regeneron Pharmaceuticals
• Original Responsible Party: Same as current
• Current Study Sponsor: Regeneron Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trial Management; Regeneron Pharmaceuticals

• PRS Account: Regeneron Pharmaceuticals
• Verification Date: March 2024