Study of REGN3767 (Anti-LAG-3) With or Without REGN2810 (Anti-PD1) in Advanced Cancers
- Registration Number
- NCT03005782
- Lead Sponsor
- Regeneron Pharmaceuticals
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 333
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Combination Therapy (REGN3767+cemiplimab) REGN3767 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 Combination Therapy (REGN3767+cemiplimab) 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 Monotherapy (REGN3767) 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.
- Primary Outcome Measures
Name Time Method Rate of dose limiting toxicities (Dose Escalation Phase) Baseline to 28 days AUCinf-to-dose ratio [AUCinf/dose] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase) Baseline to 51 weeks 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 AUC from time zero extrapolated to infinity [AUCinf] (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 Last positive (quantifiable) concentration [Clast] (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 Time of the last positive (quantifiable) concentration [tlast] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase) Baseline to 51 weeks Objective response rate by Lugano criteria for Lymphoma (Dose Expansion 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 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 t1/2 beta (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 Cmax-to-dose ratio [Cmax/dose] (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 Time to Cmax [tmax] (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
- Secondary Outcome Measures
Name Time Method 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 Best overall response based on Lugano criteria (Dose Escalation Phase) Baseline to 51 weeks 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 Disease control rate based on RECIST criteria (Dose Escalation Phase) Baseline to 51 weeks 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 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 Lugano criteria (Dose Escalation Phase) Baseline to 51 weeks Disease control rate based on irRECIST 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 Incidence of anti-drug antibodies (Dose Escalation Phase and 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
Trial Locations
- Locations (43)
Rutgers Cancer Institute of New Jersey
🇺🇸New Brunswick, New Jersey, United States
California Pacific Medical Center (CPMC)
🇺🇸San Francisco, California, United States
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
Stephenson Cancer Center
🇺🇸Oklahoma City, Oklahoma, United States
Miami Cancer Institute
🇺🇸Miami, Florida, United States
Winship Cancer Institute at Emory University
🇺🇸Atlanta, Georgia, United States
Royal Brisbane and Women's Hospital
🇦🇺Brisbane, Australia
California Cancer Associates For Research And Excellence
🇺🇸Fresno, California, United States
California Cancer Associates for Research and Excellence
🇺🇸Encinitas, California, United States
The Angeles Clinic
🇺🇸Los Angeles, California, United States
Lombardi Comprehensive Cancer Center - MedStar Georgetown University Hospital
🇺🇸Washington, District of Columbia, United States
University of California San Diego (UCSD)
🇺🇸La Jolla, California, United States
Henry Ford Health Hospital
🇺🇸Detroit, Michigan, United States
Cancer and Hematology Centers of Western Michigan
🇺🇸Grand Rapids, Michigan, United States
Washington University in Saint Louis
🇺🇸Saint Louis, Missouri, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
South Texas Oncology and Hematology
🇺🇸San Antonio, Texas, United States
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
St. Vincents University Hospital
🇮🇪Dublin, Ireland
Peter Maccallum Cancer Centre (PMCC)
🇦🇺Melbourne, Australia
University Of Oxford - Churchill Hospital
🇬🇧Headington, Oxford, United Kingdom
Laura & Isaac Perlmutter Cancer Center
🇺🇸New York, New York, United States
Columbia University
🇺🇸New York, New York, United States
Northwell Health-Monter Cancer Center
🇺🇸Lake Success, New York, United States
Dana Farber Cancer Institute
🇺🇸Jamaica Plain, Massachusetts, United States
John Theurer Cancer Center, Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
New Mexico Cancer Care Alliance-UNM Cancer Center
🇺🇸Albuquerque, New Mexico, United States
Levine Cancer Institute
🇺🇸Charlotte, North Carolina, United States
University Hospitals Seidman Cancer Center and Case Western Reserve University
🇺🇸Cleveland, Ohio, United States
The University of Western Australia - The Queen Elizabeth II Medical Centre (QEIIMC) - Sir Charles Gairdner Hospital (SCGH)
🇦🇺Perth, Western Australia, Australia
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
University of Kansas Clinical Research Center
🇺🇸Fairway, Kansas, United States
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Virginia Cancer Care Specialist, PC
🇺🇸Fairfax, Virginia, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States
Hollings Cancer Center - Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
University of California Davis Health Systems
🇺🇸Sacramento, California, United States
University of Colorado Cancer Center
🇺🇸Aurora, Colorado, United States
Orlando Health, Inc
🇺🇸Orlando, Florida, United States
Guy's Hospital
🇬🇧London, Europe, United Kingdom
Rhode Island Hospital
🇺🇸Providence, Rhode Island, United States