Clinical trial NCT03005782: Study of REGN3767 (Anti-LAG-3) With or Without REGN2810 (Anti-PD1) in Advanced Cancers
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Malignancies
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2016-12-29
Enrollment: 333
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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

Primary outcomes:
measure: Rate of dose limiting toxicities (Dose Escalation Phase)
timeFrame: Baseline to 28 days
measure: Rate of adverse events (Dose Escalation Phase)
timeFrame: Baseline to 51 weeks
measure: Rate of serious adverse events (Dose Escalation Phase)
timeFrame: Baseline to 51 weeks
measure: Occurrence of death (Dose Escalation Phase)
timeFrame: Baseline to 51 weeks
measure: Number of patients with laboratory abnormalities (grade 3 or higher per Common Terminology Criteria for Adverse Events [CTCAE]) (Dose Escalation Phase)
timeFrame: Baseline to 51 weeks
measure: 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)
timeFrame: Baseline to 51 weeks
measure: AUCall-to-dose ratio [AUCall/Dose] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)
timeFrame: Baseline to 51 weeks
measure: AUC from time zero extrapolated to infinity [AUCinf] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)
timeFrame: Baseline to 51 weeks
measure: AUCinf-to-dose ratio [AUCinf/dose] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)
timeFrame: Baseline to 51 weeks
measure: AUC computed from time zero to the time of the last positive concentration [AUClast] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)
timeFrame: Baseline to 51 weeks
measure: AUClast-to-dose ratio [AUClast/dose] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)
timeFrame: Baseline to 51 weeks
measure: Clearance [CL] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)
timeFrame: Baseline to 51 weeks
measure: Maximum Plasma Concentration [Cmax] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)
timeFrame: Baseline to week 51
measure: Cmax-to-dose ratio [Cmax/dose] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)
timeFrame: Baseline to 51 weeks
measure: Last positive (quantifiable) concentration [Clast] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)
timeFrame: Baseline to 51 weeks
measure: Mean residence time extrapolated to infinity [MRTinf] (Dose Escalation Phase)
timeFrame: Baseline to 51 weeks
measure: 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)
timeFrame: Baseline to 51 weeks
measure: Observed terminal half-life [t1/2] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)
timeFrame: Baseline to 51 weeks
measure: t1/2 beta (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)
timeFrame: Baseline to 51 weeks
measure: Time of the last positive (quantifiable) concentration [tlast] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)
timeFrame: Baseline to 51 weeks
measure: Time to Cmax [tmax] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)
timeFrame: Baseline to 51 weeks
measure: Volume of distribution at steady state [Vss] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)
timeFrame: Baseline to 51 weeks
measure: Volume of distribution of the terminal phase [Vz] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)
timeFrame: Baseline to 51 weeks
measure: Objective response rate based on RECIST 1.1 for Solid Tumors (Dose Expansion phase)
timeFrame: Baseline to 51 weeks
measure: Objective response rate by Lugano criteria for Lymphoma (Dose Expansion Phase)
timeFrame: Baseline to 51 weeks
Secondary outcomes:
measure: Objective response rate per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (solid tumors) (Dose Escalation Phase)
timeFrame: Baseline to week 51
measure: Objective response rate per Lugano criteria (lymphomas) (Dose Escalation Phase)
timeFrame: Baseline to week 51
measure: Best overall response based on RECIST 1.1 criteria (Dose Escalation Phase)
timeFrame: Baseline to 51 weeks
measure: Best overall response based on irRECIST criteria (Dose Escalation Phase)
timeFrame: Baseline to 51 weeks
measure: Best overall response based on Lugano criteria (Dose Escalation Phase)
timeFrame: Baseline to 51 weeks
measure: Duration of response based on RECIST criteria (Dose Escalation Phase)
timeFrame: Baseline to week 51
measure: Duration of response based on irRECIST criteria (Dose Escalation Phase)
timeFrame: Baseline to week 51
measure: Duration of response based on Lugano criteria (Dose Escalation Phase)
timeFrame: Baseline to week 51
measure: Disease control rate based on RECIST criteria (Dose Escalation Phase)
timeFrame: Baseline to 51 weeks
measure: Disease control rate based on irRECIST criteria (Dose Escalation Phase)
timeFrame: Baseline to 51 weeks
measure: Disease control rate based on Lugano criteria (Dose Escalation Phase)
timeFrame: Baseline to 51 weeks
measure: Progression free survival based on RECIST (Dose Escalation Phase)
timeFrame: Baseline to 51 weeks
measure: Progression free survival based on irRECIST (Dose Escalation Phase)
timeFrame: Baseline to 51 weeks
measure: Progression free survival based on Lugano criteria (Dose Escalation Phase)
timeFrame: Baseline to 51 weeks
measure: Incidence of adverse events (Dose Expansion Phase)
timeFrame: Baseline to 51 weeks
measure: Incidence of serious adverse events (Dose Expansion Phase)
timeFrame: Baseline to 51 weeks
measure: Incidence of death (Dose Expansion Phase)
timeFrame: From Baseline to the date of first documented progression or date of death from any cause, whichever comes first, assessed up to 42 months
measure: Number of patients with laboratory abnormalities (grade 3 or higher per Common Terminology Criteria for Adverse Events [CTCAE]) (Dose Expansion Phase)
timeFrame: Baseline to 51 weeks
measure: Incidence of anti-drug antibodies (Dose Escalation Phase and Dose Expansion Phase)
timeFrame: Baseline to 51 weeks
Other outcomes:
Locations:
city: Encinitas
country: United States
facility: California Cancer Associates for Research and Excellence
state: California
city: Fresno
country: United States
facility: California Cancer Associates For Research And Excellence
state: California
city: La Jolla
country: United States
facility: University of California San Diego (UCSD)
state: California
city: Los Angeles
country: United States
facility: The Angeles Clinic
state: California
city: Sacramento
country: United States
facility: University of California Davis Health Systems
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center (CPMC)
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: Washington
country: United States
facility: Lombardi Comprehensive Cancer Center - MedStar Georgetown University Hospital
state: District of Columbia
city: Miami
country: United States
facility: Miami Cancer Institute
state: Florida
city: Orlando
country: United States
facility: Orlando Health, Inc
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute at Emory University
state: Georgia
city: Fairway
country: United States
facility: University of Kansas Clinical Research Center
state: Kansas
city: Jamaica Plain
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health Hospital
state: Michigan
city: Grand Rapids
country: United States
facility: Cancer and Hematology Centers of Western Michigan
state: Michigan
city: Saint Louis
country: United States
facility: Washington University in Saint Louis
state: Missouri
city: Hackensack
country: United States
facility: John Theurer Cancer Center, Hackensack University Medical Center
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: Albuquerque
country: United States
facility: New Mexico Cancer Care Alliance-UNM Cancer Center
state: New Mexico
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Lake Success
country: United States
facility: Northwell Health-Monter Cancer Center
state: New York
city: New York
country: United States
facility: Laura & Isaac Perlmutter Cancer Center
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals Seidman Cancer Center and Case Western Reserve University
state: Ohio
city: Oklahoma City
country: United States
facility: Stephenson Cancer Center
state: Oklahoma
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Charleston
country: United States
facility: Hollings Cancer Center - Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: South Texas Oncology and Hematology
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Care Specialist, PC
state: Virginia
city: Perth
country: Australia
facility: The University of Western Australia - The Queen Elizabeth II Medical Centre (QEIIMC) - Sir Charles Gairdner Hospital (SCGH)
state: Western Australia
city: Brisbane
country: Australia
facility: Royal Brisbane and Women's Hospital
city: Melbourne
country: Australia
facility: Peter Maccallum Cancer Centre (PMCC)
city: Dublin
country: Ireland
facility: St. Vincents University Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: London
country: United Kingdom
facility: Guy's Hospital
state: Europe
city: Headington
country: United Kingdom
facility: University Of Oxford - Churchill Hospital
state: Oxford
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: