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NCT03972657PHASE1, PHASE2Recruiting

A Trial to Find Out if REGN5678 (Nezastomig) is Safe and How Well it Works Alone or in Combination With Cemiplimab for Adult Participants With Metastatic Castration-Resistant Prostate Cancer and Other Tumors

Regeneron Pharmaceuticals

Start Date

8/12/2019

Completion Date

11/15/2027

Summary

The main purpose of this study is to determine the safety, tolerability (how the body reacts to the drug\[s\]) and effectiveness (ability to treat the cancer) of REGN5678 (Nezastomig) alone, or in combination with cemiplimab. The study has 2 parts. The goal of Part 1 (dose escalation) is to determine a safe dose(s) of REGN5678 when it is given alone or in combination with cemiplimab. The goal of Part 2 (dose expansion) is to use the REGN5678 drug dose(s) found in Part 1 to see how well REGN5678 alone or in combination with cemiplimab works to shrink tumors. This study is looking at several other research questions, including: 1. Side effects that may be experienced by taking REGN5678 alone or in combination with cemiplimab 2. How REGN5678 alone or in combination with cemiplimab works in the body 3. How much REGN5678 and/or cemiplimab are present in the blood 4. To see if REGN5678 alone or in combination with cemiplimab works to reduce the size of the tumor by helping the immune system destroy the tumor

Eligibility Criteria

Age Range: 18 years to No maximum

Key Inclusion Criteria: mCRPC cohorts (men): 1. Men with histologically or cytologically confirmed adenocarcinoma of the prostate without pure small cell carcinoma. 2. PSA value at screening ≥4 ng/mL that has progressed within 6 months prior to screening as defined in the protocol. 3. Has received ≥2 lines prior systemic therapy approved in the metastatic and/or castration-resistant setting (in addition to Androgen Deprivation Therapy \[ADT\]) including at least: 1. one second-generation anti-androgen therapy (eg, abiraterone, enzalutamide, apalutamide, or darolutamide) 2. 177Lu-PSMA-617 radiotherapy, or another lutetium-based PSMA targeted radioligand, as described in the protocol ccRCC cohorts (men and women): 1. Histologically or cytologically confirmed RCC with a clear-cell component. 2. Diagnosis of metastatic ccRCC with at least one measurable lesion via RECIST 1.1 criteria 3. Has progressed on or after ≥1 line prior systemic therapy approved in the metastatic setting. Prior treatment must include an anti-Programmed Death-1 (receptor) \[PD-1\]/Programmed Death-Ligand 1 (PD-L1) therapy and either ipilimumab and/or a tyrosine kinase inhibitor Key Exclusion Criteria: 1. Has received treatment with an approved systemic therapy within 3 weeks of dosing or has not yet recovered (ie, grade ≤1 or baseline) from any acute toxicities, as described in the protocol 2. Has received any previous systemic biologic therapy within 5 half-lives of first dose of study therapy, as described in the protocol 3. Has received prior PSMA-targeting therapy with the exception of a PSMA targeting radioligand (eg. 177Lu-PSMA-617) in mCRPC 4. Dose Escalation: Has had prior anti-cancer immunotherapy (other than sipuleucel-T) within 5 half-lives prior to study therapy. 5. Dose Expansion (mCRPC only): Has had prior anti-cancer immunotherapy, as described in the protocol 6. Any condition that requires ongoing/continuous corticosteroid therapy (\>10 mg prednisone/day or anti-inflammatory equivalent) within 1 week prior to the first dose of study therapy 7. Ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, as described in the protocol 8. Encephalitis, meningitis, neurodegenerative disease (with the exception of mild dementia that does not interfere with Activities of Daily Living \[ADLs\]) or uncontrolled seizures in the year prior to first dose of study therapy 9. Uncontrolled infection with Human Immunodeficiency Virus (HIV), hepatitis B or hepatitis C infection; or diagnosis of immunodeficiency NOTE: Other protocol defined Inclusion/Exclusion Criteria apply

Interventions

DRUG

REGN5678

DRUG

Cemiplimab

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Conditions

Metastatic Castration-Resistant Prostate Cancer (mCRPC)Clear Cell Renal Cell Carcinoma (ccRCC)

Locations

Banner MD Anderson Cancer Center

Gilbert, Arizona 85234

United States

Mayo Clinic

Phoenix, Arizona 85054

United States

University of Arizona

Tucson, Arizona 85724

United States

John Wayne Cancer Institute (JWCI)

Santa Monica, California 90404

United States

Sarah Cannon Research Institute (SCRI)

Denver, Colorado 80218

United States

Yale University Hospital

New Haven, Connecticut 06510

United States

Mayo Clinic Jacksonville

Jacksonville, Florida 32224

United States

Moffitt Cancer Center - McKinley Drive

Tampa, Florida 33612

United States

Massachusetts General Hospital

Boston, Massachusetts 02114

United States

Henry Ford Health

Detroit, Michigan 48202

United States

Mayo Clinic

Rochester, Minnesota 55905

United States

NYU Langone Health Perlmutter Cancer Center

New York, New York 10016

United States

Icahn School of Medicine at Mount Sinai

New York, New York 10029

United States

Columbia University - The Trustees of Columbia University in the City of New York

New York, New York 10032

United States

Montefiore Medical Center

New York, New York 10461

United States

University of Rochester Medical Center (URMC) - Wilmot Cancer Institute (WCI) (James P. Wilmot Cancer Center) - Rochester

Rochester, New York 14642

United States

James Cancer Hospital and Solove Research Institute

Columbus, Ohio 43210

United States

Providence Portland Medical Center

Portland, Oregon 97213

United States

Oregon Health & Science University (3485 S. Bond)

Portland, Oregon 97239

United States

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania 19107

United States

Lifespan Cancer Institute

Providence, Rhode Island 02903

United States

MD Anderson Cancer Center

Houston, Texas 77030

United States

Emily Couric Clinical Cancer Center

Charlottesville, Virginia 22908

United States

West Virginia University

Morgantown, West Virginia 26506

United States