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

Regeneron Pharmaceuticals333 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

333

Conditions

Malignancies

Interventions

REGN3767DRUG

cemiplimabDRUG

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (43)

Outcomes

Primary Outcomes

Rate of dose limiting toxicities (Dose Escalation Phase)

Time frame: Baseline to 28 days

Rate of adverse events (Dose Escalation Phase)

Time frame: Baseline to 51 weeks

Rate of serious adverse events (Dose Escalation Phase)

Time frame: Baseline to 51 weeks

Occurrence of death (Dose Escalation Phase)

Time frame: 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)

Time frame: 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)

Time frame: Baseline to 51 weeks

AUCall-to-dose ratio [AUCall/Dose] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)

Time frame: Baseline to 51 weeks

AUC from time zero extrapolated to infinity [AUCinf] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)

Time frame: Baseline to 51 weeks

AUCinf-to-dose ratio [AUCinf/dose] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)

Time frame: 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)

Time frame: Baseline to 51 weeks

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

California Cancer Associates for Research and Excellence

Encinitas, California, United States

California Cancer Associates For Research And Excellence

Fresno, California, United States

University of California San Diego (UCSD)

La Jolla, California, United States

The Angeles Clinic

Los Angeles, California, United States

University of California Davis Health Systems

Sacramento, California, United States

California Pacific Medical Center (CPMC)

San Francisco, California, United States

University of Colorado Cancer Center

Aurora, Colorado, United States

Lombardi Comprehensive Cancer Center - MedStar Georgetown University Hospital

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

Miami Cancer Institute

Miami, Florida, United States

Orlando Health, Inc

Orlando, Florida, United States

...and 33 more locations

AUClast-to-dose ratio [AUClast/dose] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)

Time frame: Baseline to 51 weeks

Clearance [CL] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)

Time frame: Baseline to 51 weeks

Maximum Plasma Concentration [Cmax] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)

Time frame: Baseline to week 51

Cmax-to-dose ratio [Cmax/dose] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)

Time frame: Baseline to 51 weeks

Last positive (quantifiable) concentration [Clast] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)

Time frame: Baseline to 51 weeks

Mean residence time extrapolated to infinity [MRTinf] (Dose Escalation Phase)

Time frame: 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)

Time frame: Baseline to 51 weeks

Observed terminal half-life [t1/2] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)

Time frame: Baseline to 51 weeks

t1/2 beta (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)

Time frame: Baseline to 51 weeks

Time of the last positive (quantifiable) concentration [tlast] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)

Time frame: Baseline to 51 weeks

Time to Cmax [tmax] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)

Time frame: Baseline to 51 weeks

Volume of distribution at steady state [Vss] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)

Time frame: Baseline to 51 weeks

Volume of distribution of the terminal phase [Vz] (Primary: Dose Escalation Phase; Secondary: Dose Expansion Phase)

Time frame: Baseline to 51 weeks

Objective response rate based on RECIST 1.1 for Solid Tumors (Dose Expansion phase)

Time frame: Baseline to 51 weeks

Objective response rate by Lugano criteria for Lymphoma (Dose Expansion Phase)

Time frame: Baseline to 51 weeks

Secondary Outcomes

Objective response rate per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (solid tumors) (Dose Escalation Phase)

Time frame: Baseline to week 51

Objective response rate per Lugano criteria (lymphomas) (Dose Escalation Phase)

Time frame: Baseline to week 51

Best overall response based on RECIST 1.1 criteria (Dose Escalation Phase)

Time frame: Baseline to 51 weeks

Best overall response based on irRECIST criteria (Dose Escalation Phase)

Time frame: Baseline to 51 weeks

Best overall response based on Lugano criteria (Dose Escalation Phase)

Time frame: Baseline to 51 weeks

Duration of response based on RECIST criteria (Dose Escalation Phase)

Time frame: Baseline to week 51

Duration of response based on irRECIST criteria (Dose Escalation Phase)

Time frame: Baseline to week 51

Duration of response based on Lugano criteria (Dose Escalation Phase)

Time frame: Baseline to week 51

Disease control rate based on RECIST criteria (Dose Escalation Phase)

Time frame: Baseline to 51 weeks

Disease control rate based on irRECIST criteria (Dose Escalation Phase)

Time frame: Baseline to 51 weeks

Disease control rate based on Lugano criteria (Dose Escalation Phase)

Time frame: Baseline to 51 weeks

Progression free survival based on RECIST (Dose Escalation Phase)

Time frame: Baseline to 51 weeks

Progression free survival based on irRECIST (Dose Escalation Phase)

Time frame: Baseline to 51 weeks

Progression free survival based on Lugano criteria (Dose Escalation Phase)

Time frame: Baseline to 51 weeks

Incidence of adverse events (Dose Expansion Phase)

Time frame: Baseline to 51 weeks

Incidence of serious adverse events (Dose Expansion Phase)

Time frame: Baseline to 51 weeks

Incidence of death (Dose Expansion Phase)

Time frame: 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)

Time frame: Baseline to 51 weeks

Incidence of anti-drug antibodies (Dose Escalation Phase and Dose Expansion Phase)

Time frame: Baseline to 51 weeks