Study of REGN3767 (Anti-LAG-3) With or Without REGN2810 (Anti-PD1) in Advanced Cancers

A Phase 1, Open-Label, Dose-Escalation and Cohort Expansion First-in-Human Study of the Safety, Tolerability, Activity and Pharmacokinetics of REGN3767 (Anti-LAG-3 mAb) Administered Alone or in Combination With REGN2810 (Anti-PD-1 mAb) in Patients With Advanced Malignancies

The primary objectives in the dose escalation phase are to evaluate safety and pharmacokinetics (PK) in order to determine the selected dose level(s) for expansion of REGN3767 as monotherapy and in combination with cemiplimab in patients with advanced malignancies, including lymphoma.

The primary objectives in the dose expansion phase are to assess preliminary anti-tumor activity of REGN3767 alone and in combination with cemiplimab (separately by cohort) as measured by objective response rate (ORR).

Study Overview

• Status: Active, not recruiting
• Conditions: Malignancies
• Intervention / Treatment: Drug: REGN3767; Drug: cemiplimab

• Study Type: Interventional
• Enrollment (Actual): 333
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Brisbane, Australia, 4029
    • Royal Brisbane and Women'S Hospital
  • Melbourne, Australia, 3000
    • Peter Maccallum Cancer Centre (PMCC)
  • Western Australia
    • Perth, Western Australia, Australia, 06009
      • The University of Western Australia - The Queen Elizabeth II Medical Centre (QEIIMC) - Sir Charles Gairdner Hospital (SCGH)
• Ireland
  • Dublin, Ireland, D04 T6F4
    • St. Vincents University Hospital
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital, Yonsei University Health System
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
• United Kingdom
  • Europe
    • London, Europe, United Kingdom, SE19RT
      • Guy's Hospital
  • Oxford
    • Headington, Oxford, United Kingdom, OX37LJ
      • University Of Oxford - Churchill Hospital
• United States
  • California
    • Encinitas, California, United States, 92024
      • California Cancer Associates for Research and Excellence
    • Fresno, California, United States, 93720
      • California Cancer Associates for Research and Excellence
    • La Jolla, California, United States, 92093-0698
      • University of California San Diego (UCSD)
    • Los Angeles, California, United States, 90025
      • The Angeles Clinic
    • Sacramento, California, United States, 95817
      • University of California Davis Health Systems
    • San Francisco, California, United States, 94115
      • California Pacific Medical Center (CPMC)
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Cancer Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Lombardi Comprehensive Cancer Center - MedStar Georgetown University Hospital
  • Florida
    • Miami, Florida, United States, 33176
      • Miami Cancer Institute
    • Orlando, Florida, United States, 32806
      • Orlando Health, Inc
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute at Emory University
  • Kansas
    • Fairway, Kansas, United States, 66205
      • University of Kansas Clinical Research Center
  • Massachusetts
    • Jamaica Plain, Massachusetts, United States, 02130
      • Dana Farber Cancer Institute
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health Hospital
    • Grand Rapids, Michigan, United States, 49503
      • Cancer and Hematology Centers of Western Michigan
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University in Saint Louis
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • John Theurer Cancer Center, Hackensack University Medical Center
    • New Brunswick, New Jersey, United States, 08903
      • Rutgers Cancer Institute of New Jersey
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • New Mexico Cancer Care Alliance-UNM Cancer Center
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • Lake Success, New York, United States, 11042
      • Northwell Health-Monter Cancer Center
    • New York, New York, United States, 10032
      • Columbia University
    • New York, New York, United States, 10065
      • Memorial Sloan-Kettering Cancer Center
    • New York, New York, United States, 10016
      • Laura & Isaac Perlmutter Cancer Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Levine Cancer Institute
  • Ohio
    • Cleveland, Ohio, United States, 44087
      • University Hospitals Seidman Cancer Center and Case Western Reserve University
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Stephenson Cancer Center
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Hollings Cancer Center - Medical University of South Carolina
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas Md Anderson Cancer Center
    • San Antonio, Texas, United States, 78229
      • South Texas Oncology and Hematology
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Care Specialist, PC

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria:

• Dose escalation cohorts: Patients with histologically or cytologically confirmed diagnosis of malignancy (including lymphoma) with demonstrated progression of a tumor for whom there is no available therapy likely to convey clinical benefit AND who have not been previously treated with a PD-1/PD-L1 inhibitor. These patients do not require measurable disease
• Dose expansion cohorts: Patients with histologically or cytologically confirmed diagnosis of 1 of specified tumors with measurable disease per RECIST 1.1 or Lugano criteria. Some patients may have been previously treated with a PD-1 or PD-L1 inhibitor
• Eastern Cooperative Oncology Group performance status of 0 or 1
• Adequate organ and bone marrow function

Key Exclusion Criteria:

• Prior treatment with any LAG-3 targeting biologic or small molecule
• Radiation therapy within 2 weeks prior to randomization and not recovered to baseline from any AE due to radiation
• Untreated or active central nervous system metastases - Ongoing or recent (within 5 years) evidence of significant autoimmune disease
• Corticosteroid therapy (>10 mg prednisone/day or equivalent) within 1 week prior to the first dose of study drug
• Myocardial infarction within 6 months

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: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Monotherapy (REGN3767); Group A will consist of up to 4 sequential dose cohorts. Each cohort will receive 1 of 3 ascending dose levels of study drug during dose escalation. In addition 1 tumor-specific cohort will be treated at the recommended phase 2 dose (RP2D) during dose expansion.	Drug: REGN3767; Other Names: fianlimab
Experimental: Combination Therapy (REGN3767+cemiplimab); Group B will consist of up to 4 sequential dose cohorts. Each cohort will receive 1 of 3 ascending dose levels of study drug during dose escalation. In addition, 9 tumor-specific cohorts will be treated at the RP2D during dose expansion	Drug: REGN3767; Other Names: fianlimab; Drug: cemiplimab; Other Names: REGN2810

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Rate of dose limiting toxicities (Dose Escalation Phase)	Baseline to 28 days
Rate of adverse events (Dose Escalation Phase)	Baseline to 51 weeks
Rate of serious adverse events (Dose Escalation Phase)	Baseline to 51 weeks
Occurrence of death (Dose Escalation Phase)	Baseline to 51 weeks
Number of patients with laboratory abnormalities (grade 3 or higher per Common Terminology Criteria for Adverse Events [CTCAE]) (Dose Escalation Phase)	Baseline to 51 weeks
Area under the curve (AUC) computed from time zero to the time of the last concentration [AUCall] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)	Baseline to 51 weeks
AUCall-to-dose ratio [AUCall/Dose] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)	Baseline to 51 weeks
AUC from time zero extrapolated to infinity [AUCinf] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)	Baseline to 51 weeks
AUCinf-to-dose ratio [AUCinf/dose] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)	Baseline to 51 weeks
AUC computed from time zero to the time of the last positive concentration [AUClast] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)	Baseline to 51 weeks
AUClast-to-dose ratio [AUClast/dose] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)	Baseline to 51 weeks
Clearance [CL] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)	Baseline to 51 weeks
Maximum Plasma Concentration [Cmax] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)	Baseline to week 51
Cmax-to-dose ratio [Cmax/dose] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)	Baseline to 51 weeks
Last positive (quantifiable) concentration [Clast] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)	Baseline to 51 weeks
Mean residence time extrapolated to infinity [MRTinf] (Dose Escalation Phase)	Baseline to 51 weeks
Mean residence time when the drug concentration profile is based on values up to and including the last positive concentration [MRTlast] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)	Baseline to 51 weeks
Observed terminal half-life [t1/2] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)	Baseline to 51 weeks
t1/2 beta (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)	Baseline to 51 weeks
Time of the last positive (quantifiable) concentration [tlast] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)	Baseline to 51 weeks
Time to Cmax [tmax] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)	Baseline to 51 weeks
Volume of distribution at steady state [Vss] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)	Baseline to 51 weeks
Volume of distribution of the terminal phase [Vz] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)	Baseline to 51 weeks
Objective response rate based on RECIST 1.1 for Solid Tumors (Dose Expansion phase)	Baseline to 51 weeks
Objective response rate by Lugano criteria for Lymphoma (Dose Expansion Phase)	Baseline to 51 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Objective response rate per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (solid tumors) (Dose Escalation Phase)	Baseline to week 51
Objective response rate per Lugano criteria (lymphomas) (Dose Escalation Phase)	Baseline to week 51
Best overall response based on RECIST 1.1 criteria (Dose Escalation Phase)	Baseline to 51 weeks
Best overall response based on irRECIST criteria (Dose Escalation Phase)	Baseline to 51 weeks
Best overall response based on Lugano criteria (Dose Escalation Phase)	Baseline to 51 weeks
Duration of response based on RECIST criteria (Dose Escalation Phase)	Baseline to week 51
Duration of response based on irRECIST criteria (Dose Escalation Phase)	Baseline to week 51
Duration of response based on Lugano criteria (Dose Escalation Phase)	Baseline to week 51
Disease control rate based on RECIST criteria (Dose Escalation Phase)	Baseline to 51 weeks
Disease control rate based on irRECIST criteria (Dose Escalation Phase)	Baseline to 51 weeks
Disease control rate based on Lugano criteria (Dose Escalation Phase)	Baseline to 51 weeks
Progression free survival based on RECIST (Dose Escalation Phase)	Baseline to 51 weeks
Progression free survival based on irRECIST (Dose Escalation Phase)	Baseline to 51 weeks
Progression free survival based on Lugano criteria (Dose Escalation Phase)	Baseline to 51 weeks
Incidence of adverse events (Dose Expansion Phase)	Baseline to 51 weeks
Incidence of serious adverse events (Dose Expansion Phase)	Baseline to 51 weeks
Incidence of death (Dose Expansion Phase)	From Baseline to the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 42 months
Number of patients with laboratory abnormalities (grade 3 or higher per Common Terminology Criteria for Adverse Events [CTCAE]) (Dose Expansion Phase)	Baseline to 51 weeks
Incidence of anti-drug antibodies (Dose Escalation Phase and Dose Expansion Phase)	Baseline to 51 weeks

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): November 7, 2016
• Primary Completion (Estimated): December 14, 2024
• Study Completion (Estimated): December 14, 2024

Study Registration Dates

• First Submitted: November 18, 2016
• First Submitted That Met QC Criteria: December 23, 2016
• First Posted (Estimated): December 29, 2016

Study Record Updates

• Last Update Posted (Actual): November 30, 2023
• Last Update Submitted That Met QC Criteria: November 29, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Cemiplimab
• Other Study ID Numbers: R3767-ONC-1613; 2016-002789-30 (EudraCT Number)