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

Malignancies Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03005782
• Other study ID #: R3767-ONC-1613
• Secondary ID: 2016-002789-30
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: November 7, 2016
• Est. completion date: December 14, 2024

Study information

• Verified date: November 2023
• Source: Regeneron Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 333
• Est. completion date: December 14, 2024
• Est. primary completion date: December 14, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Malignancies
• Neoplasms

Intervention

Drug:
• REGN3767

• cemiplimab

Locations

Country	Name	City	State
Australia	Royal Brisbane and Women's Hospital	Brisbane
Australia	Peter Maccallum Cancer Centre (PMCC)	Melbourne
Australia	The University of Western Australia - The Queen Elizabeth II Medical Centre (QEIIMC) - Sir Charles Gairdner Hospital (SCGH)	Perth	Western Australia
Ireland	St. Vincents University Hospital	Dublin
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
United Kingdom	University Of Oxford - Churchill Hospital	Headington	Oxford
United Kingdom	Guy's Hospital	London	Europe
United States	New Mexico Cancer Care Alliance-UNM Cancer Center	Albuquerque	New Mexico
United States	Winship Cancer Institute at Emory University	Atlanta	Georgia
United States	University of Colorado Cancer Center	Aurora	Colorado
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Hollings Cancer Center - Medical University of South Carolina	Charleston	South Carolina
United States	Levine Cancer Institute	Charlotte	North Carolina
United States	University Hospitals Seidman Cancer Center and Case Western Reserve University	Cleveland	Ohio
United States	Henry Ford Health Hospital	Detroit	Michigan
United States	California Cancer Associates for Research and Excellence	Encinitas	California
United States	Virginia Cancer Care Specialist, PC	Fairfax	Virginia
United States	University of Kansas Clinical Research Center	Fairway	Kansas
United States	California Cancer Associates For Research And Excellence	Fresno	California
United States	Cancer and Hematology Centers of Western Michigan	Grand Rapids	Michigan
United States	John Theurer Cancer Center, Hackensack University Medical Center	Hackensack	New Jersey
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Dana Farber Cancer Institute	Jamaica Plain	Massachusetts
United States	University of California San Diego (UCSD)	La Jolla	California
United States	Northwell Health-Monter Cancer Center	Lake Success	New York
United States	The Angeles Clinic	Los Angeles	California
United States	Miami Cancer Institute	Miami	Florida
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey
United States	Columbia University	New York	New York
United States	Laura & Isaac Perlmutter Cancer Center	New York	New York
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	Orlando Health, Inc	Orlando	Florida
United States	Rhode Island Hospital	Providence	Rhode Island
United States	University of California Davis Health Systems	Sacramento	California
United States	Washington University in Saint Louis	Saint Louis	Missouri
United States	South Texas Oncology and Hematology	San Antonio	Texas
United States	California Pacific Medical Center (CPMC)	San Francisco	California
United States	Lombardi Comprehensive Cancer Center - MedStar Georgetown University Hospital	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals	Sanofi

Countries where clinical trial is conducted

United States,  Australia,  Ireland,  Korea, Republic of,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of dose limiting toxicities (Dose Escalation Phase)		Baseline to 28 days
Primary	Rate of adverse events (Dose Escalation Phase)		Baseline to 51 weeks
Primary	Rate of serious adverse events (Dose Escalation Phase)		Baseline to 51 weeks
Primary	Occurrence of death (Dose Escalation Phase)		Baseline to 51 weeks
Primary	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
Primary	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
Primary	AUCall-to-dose ratio [AUCall/Dose] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)		Baseline to 51 weeks
Primary	AUC from time zero extrapolated to infinity [AUCinf] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)		Baseline to 51 weeks
Primary	AUCinf-to-dose ratio [AUCinf/dose] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)		Baseline to 51 weeks
Primary	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
Primary	AUClast-to-dose ratio [AUClast/dose] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)		Baseline to 51 weeks
Primary	Clearance [CL] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)		Baseline to 51 weeks
Primary	Maximum Plasma Concentration [Cmax] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)		Baseline to week 51
Primary	Cmax-to-dose ratio [Cmax/dose] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)		Baseline to 51 weeks
Primary	Last positive (quantifiable) concentration [Clast] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)		Baseline to 51 weeks
Primary	Mean residence time extrapolated to infinity [MRTinf] (Dose Escalation Phase)		Baseline to 51 weeks
Primary	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
Primary	Observed terminal half-life [t1/2] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)		Baseline to 51 weeks
Primary	t1/2 beta (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)		Baseline to 51 weeks
Primary	Time of the last positive (quantifiable) concentration [tlast] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)		Baseline to 51 weeks
Primary	Time to Cmax [tmax] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)		Baseline to 51 weeks
Primary	Volume of distribution at steady state [Vss] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)		Baseline to 51 weeks
Primary	Volume of distribution of the terminal phase [Vz] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)		Baseline to 51 weeks
Primary	Objective response rate based on RECIST 1.1 for Solid Tumors (Dose Expansion phase)		Baseline to 51 weeks
Primary	Objective response rate by Lugano criteria for Lymphoma (Dose Expansion Phase)		Baseline to 51 weeks
Secondary	Objective response rate per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (solid tumors) (Dose Escalation Phase)		Baseline to week 51
Secondary	Objective response rate per Lugano criteria (lymphomas) (Dose Escalation Phase)		Baseline to week 51
Secondary	Best overall response based on RECIST 1.1 criteria (Dose Escalation Phase)		Baseline to 51 weeks
Secondary	Best overall response based on irRECIST criteria (Dose Escalation Phase)		Baseline to 51 weeks
Secondary	Best overall response based on Lugano criteria (Dose Escalation Phase)		Baseline to 51 weeks
Secondary	Duration of response based on RECIST criteria (Dose Escalation Phase)		Baseline to week 51
Secondary	Duration of response based on irRECIST criteria (Dose Escalation Phase)		Baseline to week 51
Secondary	Duration of response based on Lugano criteria (Dose Escalation Phase)		Baseline to week 51
Secondary	Disease control rate based on RECIST criteria (Dose Escalation Phase)		Baseline to 51 weeks
Secondary	Disease control rate based on irRECIST criteria (Dose Escalation Phase)		Baseline to 51 weeks
Secondary	Disease control rate based on Lugano criteria (Dose Escalation Phase)		Baseline to 51 weeks
Secondary	Progression free survival based on RECIST (Dose Escalation Phase)		Baseline to 51 weeks
Secondary	Progression free survival based on irRECIST (Dose Escalation Phase)		Baseline to 51 weeks
Secondary	Progression free survival based on Lugano criteria (Dose Escalation Phase)		Baseline to 51 weeks
Secondary	Incidence of adverse events (Dose Expansion Phase)		Baseline to 51 weeks
Secondary	Incidence of serious adverse events (Dose Expansion Phase)		Baseline to 51 weeks
Secondary	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
Secondary	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
Secondary	Incidence of anti-drug antibodies (Dose Escalation Phase and Dose Expansion Phase)		Baseline to 51 weeks