A Trial to Find Out if REGN5678 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
- Conditions
- Metastatic Castration-resistant Prostate Cancer (mCRPC)Clear Cell Renal Cell Carcinoma (ccRCC)
- Interventions
- Registration Number
- NCT03972657
- Lead Sponsor
- Regeneron Pharmaceuticals
- Brief Summary
The main purpose of this study is to determine the safety, tolerability (how your body reacts to the drug) and effectiveness (ability to treat your cancer) of REGN5678 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Male
- Target Recruitment
- 345
mCRPC cohorts:
-
Men with histologically or cytologically confirmed adenocarcinoma of the prostate without pure small cell carcinoma.
-
Prostate specific antigen (PSA) value at screening ≥4 ng/mL that has progressed within 6 months prior to screening as defined in the protocol.
-
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:
- one second-generation anti-androgen therapy (eg, abiraterone, enzalutamide, apalutamide, or darolutamide)
- post-177Lu-PSMA-617 radiotherapy expansion cohort only. Must have received at least 2 doses of 177Lu-PSMA-617.
ccRCC cohorts:
- Men and women with histologically or cytologically confirmed RCC with a clear-cell component.
- Diagnosis of metastatic ccRCC with at least one measurable lesion via RECIST 1.1 criteria
- 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
- 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
- Has received any previous systemic biologic therapy within 5 half-lives of first dose of study therapy, as described in the protocol
- Has received prior PSMA-targeting therapy with the exception of approved radiopharmaceutical therapy (eg. 177Lu-PSMA-617) in mCRPC patients
- Dose Escalation: Has had prior anti-cancer immunotherapy (other than sipuleucel-T) within 5 half-lives prior to study therapy.
- Dose Expansion (mCRPC only): Has had prior anti-cancer immunotherapy, as describe in the protocol
- 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
- Ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description mCRPC - dose expansion cohort REGN5678 Participants will receive the REGN5678 presumptive RP2D(s) ccRCC - dose expansion cohort REGN5678 Participants will receive the REGN5678 presumptive RP2D(s) mCRPC - dose escalation cohort REGN5678 Participants will receive REGN5678 monotherapy for presumptive recommended phase 2 dose(s) (presumptive RP2D) identification Note: Dose escalation on monotherapy lead-in of REGN5678 followed by combination therapy of REGN5678 with full dose cemiplimab is no longer actively enrolling new participants. The prophylactic use of sarilumab is no longer in use. ccRCC - dose escalation cohort REGN5678 Participants will receive REGN5678 monotherapy for presumptive RP2D identification Note: Dose escalation on monotherapy lead-in of REGN5678 followed by combination therapy of REGN5678 with full dose cemiplimab is no longer actively enrolling new participants. The prophylactic use of sarilumab is no longer in use. mCRPC - dose escalation cohort Cemiplimab Participants will receive REGN5678 monotherapy for presumptive recommended phase 2 dose(s) (presumptive RP2D) identification Note: Dose escalation on monotherapy lead-in of REGN5678 followed by combination therapy of REGN5678 with full dose cemiplimab is no longer actively enrolling new participants. The prophylactic use of sarilumab is no longer in use. ccRCC - dose escalation cohort Cemiplimab Participants will receive REGN5678 monotherapy for presumptive RP2D identification Note: Dose escalation on monotherapy lead-in of REGN5678 followed by combination therapy of REGN5678 with full dose cemiplimab is no longer actively enrolling new participants. The prophylactic use of sarilumab is no longer in use.
- Primary Outcome Measures
Name Time Method Incidence and severity of adverse event of special interests (AESIs) Through study completion, Up to 5 years Dose Escalation Phase
Incidence and severity of serious adverse events (SAEs) Through study completion, Up to 5 years Dose Escalation Phase
ORR per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria Through study completion, Up to 5 years Dose Expansion Phase - ccRCC cohort
Number of participants with Grade ≥3 laboratory abnormalities Through study completion, Up to 5 years Dose Escalation Phase
Objective response rate (ORR) per modified Prostate Cancer Working Group 3 (PCWG3) criteria Through study completion, Up to 5 years Dose Expansion Phase - mCRPC cohort
Incidence and severity of treatment-emergent adverse events (TEAEs) Through study completion, Up to 5 years Dose Escalation Phase
Concentration of REGN5678 in serum over time Through study completion, Up to 5 years Dose Escalation Phase
Incidence of dose-limiting toxicities (DLTs) First dose through day 42 of last participant in each dose level Dose Escalation Phase
Concentration of REGN5678 in combination with cemiplimab in serum over time Through study completion, Up to 5 years Dose Escalation Phase
- Secondary Outcome Measures
Name Time Method Concentration of REGN5678 in combination with cemiplimab in serum over time Through study completion, Up to 5 years Dose Expansion Phase
Presence or absence of antibodies against REGN5678 Through study completion, Up to 5 years Dose Escalation and Dose Expansion Phases
ORR per RECIST 1.1 criteria Through study completion, Up to 5 years Dose Escalation Phase - ccRCC cohort
ORR based upon prostate specific antigen (PSA) response Through study completion, Up to 5 years Dose Escalation and Dose Expansion Phases - mCRPC cohorts
Presence or absence of antibodies against cemiplimab Through study completion, Up to 5 years Dose Escalation and Dose Expansion Phases
Incidence and severity of AESIs Through study completion, Up to 5 years Dose Expansion Phase
ORR per modified PCWG3 criteria Through study completion, Up to 5 years Dose Escalation Phase - mCRPC cohort
Concentration of REGN5678 in serum over time Through study completion, Up to 5 years Dose Expansion Phase
Incidence and severity of TEAEs Through study completion, Up to 5 years Dose Expansion Phase
Incidence and severity of SAEs Through study completion, Up to 5 years Dose Expansion Phase
Percentage of participants with ≥90% decline of PSA Through study completion, Up to 5 years Dose Escalation and Dose Expansion Phases- mCRPC cohorts
Number of participants with grade ≥3 laboratory abnormalities Through study completion, Up to 5 years Dose Expansion Phase
Trial Locations
- Locations (17)
University of Arizona
🇺🇸Tucson, Arizona, United States
John Wayne Cancer Institute (JWCI)
🇺🇸Santa Monica, California, United States
Sarah Cannon Research Institute (SCRI)
🇺🇸Denver, Colorado, United States
Yale University Hospital
🇺🇸New Haven, Connecticut, United States
Banner MD Anderson Cancer Center
🇺🇸Gilbert, Arizona, United States
Moffitt Cancer Center - McKinley Drive
🇺🇸Tampa, Florida, United States
Icahn School of Medicine at Mount Sinai
🇺🇸New York, New York, United States
Columbia University - The Trustees of Columbia University in the City of New York
🇺🇸New York, New York, United States
Oregon Health & Science University (3485 S. Bond)
🇺🇸Portland, Oregon, United States
Lifespan Cancer Institute
🇺🇸Providence, Rhode Island, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Emily Couric Clinical Cancer Center
🇺🇸Charlottesville, Virginia, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
NYU Langone Health Perlmutter Cancer Center
🇺🇸New York, New York, United States
Montefiore Medical Center
🇺🇸New York, New York, United States
Providence Portland Medical Center
🇺🇸Portland, Oregon, United States
Thomas Jefferson University Hospital
🇺🇸Philadelphia, Pennsylvania, United States