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

NCT03005782 | Completed Phase 1 DMC

• 2 other identifiers: R3767-ONC-16132016-002789-30
• Study Type: interventional
• Target: 333
• Locations: 5 countries
• Sites: 43

Brief Summary

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).

Conditions

Malignancies

Outcome Measures

Primary Outcomes (25)

• 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 Outcomes (19)

• 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

Study Arms (2)

Monotherapy (REGN3767)

EXPERIMENTAL

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

Combination Therapy (REGN3767+cemiplimab)

EXPERIMENTAL

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; Drug: cemiplimab

Interventions

REGN3767 DRUG

Also known as: fianlimab

Combination Therapy (REGN3767+cemiplimab); Monotherapy (REGN3767)

cemiplimab DRUG

Also known as: REGN2810

Combination Therapy (REGN3767+cemiplimab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead

Study Sites (43)

California Cancer Associates for Research and Excellence

Encinitas, California, 92024, United States

Location

California Cancer Associates For Research And Excellence

Fresno, California, 93720, United States

Location

University of California San Diego (UCSD)

La Jolla, California, 92093-0698, United States

Location

The Angeles Clinic

Los Angeles, California, 90025, United States

Location

University of California Davis Health Systems

Sacramento, California, 95817, United States

Location

California Pacific Medical Center (CPMC)

San Francisco, California, 94115, United States

Location

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

Location

Lombardi Comprehensive Cancer Center - MedStar Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

Miami Cancer Institute

Miami, Florida, 33176, United States

Location

Orlando Health, Inc

Orlando, Florida, 32806, United States

Location

Winship Cancer Institute at Emory University

Atlanta, Georgia, 30322, United States

Location

University of Kansas Clinical Research Center

Fairway, Kansas, 66205, United States

Location

Dana Farber Cancer Institute

Jamaica Plain, Massachusetts, 02130, United States

Location

Henry Ford Health Hospital

Detroit, Michigan, 48202, United States

Location

Cancer and Hematology Centers of Western Michigan

Grand Rapids, Michigan, 49503, United States

Location

Washington University in Saint Louis

St Louis, Missouri, 63110, United States

Location

John Theurer Cancer Center, Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

New Mexico Cancer Care Alliance-UNM Cancer Center

Albuquerque, New Mexico, 87131, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Northwell Health-Monter Cancer Center

Lake Success, New York, 11042, United States

Location

Laura & Isaac Perlmutter Cancer Center

New York, New York, 10016, United States

Location

Columbia University

New York, New York, 10032, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

University Hospitals Seidman Cancer Center and Case Western Reserve University

Cleveland, Ohio, 44087, United States

Location

Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

Hollings Cancer Center - Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

South Texas Oncology and Hematology

San Antonio, Texas, 78229, United States

Location

Virginia Cancer Care Specialist, PC

Fairfax, Virginia, 22031, United States

Location

The University of Western Australia - The Queen Elizabeth II Medical Centre (QEIIMC) - Sir Charles Gairdner Hospital (SCGH)

Perth, Western Australia, 06009, Australia

Location

Royal Brisbane and Women's Hospital

Brisbane, 4029, Australia

Location

Peter Maccallum Cancer Centre (PMCC)

Melbourne, 3000, Australia

Location

St. Vincents University Hospital

Dublin, D04 T6F4, Ireland

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Guy's Hospital

London, Europe, SE19RT, United Kingdom

Location

University Of Oxford - Churchill Hospital

Headington, Oxford, OX37LJ, United Kingdom

Location

Related Publications (1)

• Hamid O, Lewis KD, Weise A, McKean M, Papadopoulos KP, Crown J, Kim TM, Lee DH, Thomas SS, Mehnert J, Kaczmar J, Lakhani NJ, Kim KB, Middleton MR, Rabinowits G, Spira AI, Yushak M, Mehmi I, Fang F, Chen S, Mani J, Jankovic V, Wang F, Fiaschi N, Brennan L, Paccaly A, Masinde S, Salvati M, Fury MG, Kroog G, Lowy I, Gullo G. Phase I Study of Fianlimab, a Human Lymphocyte Activation Gene-3 (LAG-3) Monoclonal Antibody, in Combination With Cemiplimab in Advanced Melanoma. J Clin Oncol. 2024 Aug 20;42(24):2928-2938. doi: 10.1200/JCO.23.02172. Epub 2024 Jun 20.

  PMID: 38900987 DERIVED

MeSH Terms

Conditions

Neoplasms

Interventions

cemiplimab

Study Officials

• Clinical Trial Management

  Regeneron Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2016
• First Posted: December 29, 2016
• Study Start: November 7, 2016
• Primary Completion: April 2, 2024
• Study Completion: April 2, 2024
• Last Updated: May 1, 2024

Record last verified: 2024-04

Locations

GB (2); US (33); AU (3); IE (1); KR (4)