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

• ClinicalTrials.gov Identifier: NCT03972657
• Recruitment Status: Recruiting
• First Posted: June 3, 2019
• Last Update Posted: March 8, 2024
• Sponsor: Regeneron Pharmaceuticals
• Information provided by (Responsible Party): Regeneron Pharmaceuticals

Study Description

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

Condition or disease	Intervention/treatment	Phase
Metastatic Castration-resistant Prostate Cancer (mCRPC); Clear Cell Renal Cell Carcinoma (ccRCC)	Drug: REGN5678; Drug: Cemiplimab	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 345 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1/2 Study of REGN5678 (Anti-PSMAxCD28) With or Without Cemiplimab (Anti-PD-1) in Patients With Metastatic Castration-Resistant Prostate Cancer and Other Tumors Associated With PSMA Expression
• Actual Study Start Date: August 12, 2019
• Estimated Primary Completion Date: August 1, 2025
• Estimated Study Completion Date: July 3, 2026

Arms and Interventions

Arm	Intervention/treatment
Experimental: mCRPC - dose escalation cohort; 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.	Drug: REGN5678; Administered at the assigned dose level (DL) by intravenous (IV) infusion or subcutaneous (SC) administration; Drug: Cemiplimab; Administered at the assigned DL by IV; Other Names: REGN2810; LIBTAYO
Experimental: mCRPC - dose expansion cohort; Participants will receive the REGN5678 presumptive RP2D(s)	Drug: REGN5678; Administered at the assigned dose level (DL) by intravenous (IV) infusion or subcutaneous (SC) administration
Experimental: ccRCC - dose escalation cohort; 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.	Drug: REGN5678; Administered at the assigned dose level (DL) by intravenous (IV) infusion or subcutaneous (SC) administration; Drug: Cemiplimab; Administered at the assigned DL by IV; Other Names: REGN2810; LIBTAYO
Experimental: ccRCC - dose expansion cohort; Participants will receive the REGN5678 presumptive RP2D(s)	Drug: REGN5678; Administered at the assigned dose level (DL) by intravenous (IV) infusion or subcutaneous (SC) administration

Outcome Measures

Primary Outcome Measures :

1. Incidence and severity of treatment-emergent adverse events (TEAEs) [ Time Frame: Through study completion, Up to 5 years ]
   Dose Escalation Phase
2. Incidence and severity of adverse event of special interests (AESIs) [ Time Frame: Through study completion, Up to 5 years ]
   Dose Escalation Phase
3. Incidence and severity of serious adverse events (SAEs) [ Time Frame: Through study completion, Up to 5 years ]
   Dose Escalation Phase
4. Number of participants with Grade ≥3 laboratory abnormalities [ Time Frame: Through study completion, Up to 5 years ]
   Dose Escalation Phase
5. Incidence of dose-limiting toxicities (DLTs) [ Time Frame: First dose through day 42 of last participant in each dose level ]
   Dose Escalation Phase
6. Concentration of REGN5678 in serum over time [ Time Frame: Through study completion, Up to 5 years ]
   Dose Escalation Phase
7. Concentration of REGN5678 in combination with cemiplimab in serum over time [ Time Frame: Through study completion, Up to 5 years ]
   Dose Escalation Phase
8. Objective response rate (ORR) per modified Prostate Cancer Working Group 3 (PCWG3) criteria [ Time Frame: Through study completion, Up to 5 years ]
   Dose Expansion Phase - mCRPC cohort
9. ORR per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria [ Time Frame: Through study completion, Up to 5 years ]
   Dose Expansion Phase - ccRCC cohort

Secondary Outcome Measures :

1. ORR per modified PCWG3 criteria [ Time Frame: Through study completion, Up to 5 years ]
   Dose Escalation Phase - mCRPC cohort
2. ORR per RECIST 1.1 criteria [ Time Frame: Through study completion, Up to 5 years ]
   Dose Escalation Phase - ccRCC cohort
3. Incidence and severity of TEAEs [ Time Frame: Through study completion, Up to 5 years ]
   Dose Expansion Phase
4. Incidence and severity of AESIs [ Time Frame: Through study completion, Up to 5 years ]
   Dose Expansion Phase
5. Incidence and severity of SAEs [ Time Frame: Through study completion, Up to 5 years ]
   Dose Expansion Phase
6. Number of participants with grade ≥3 laboratory abnormalities [ Time Frame: Through study completion, Up to 5 years ]
   Dose Expansion Phase
7. Concentration of REGN5678 in serum over time [ Time Frame: Through study completion, Up to 5 years ]
   Dose Expansion Phase
8. Concentration of REGN5678 in combination with cemiplimab in serum over time [ Time Frame: Through study completion, Up to 5 years ]
   Dose Expansion Phase
9. ORR based upon prostate specific antigen (PSA) response [ Time Frame: Through study completion, Up to 5 years ]
   Dose Escalation and Dose Expansion Phases - mCRPC cohorts
10. Percentage of participants with ≥90% decline of PSA [ Time Frame: Through study completion, Up to 5 years ]
    Dose Escalation and Dose Expansion Phases- mCRPC cohorts
11. Presence or absence of antibodies against REGN5678 [ Time Frame: Through study completion, Up to 5 years ]
    Dose Escalation and Dose Expansion Phases
12. Presence or absence of antibodies against cemiplimab [ Time Frame: Through study completion, Up to 5 years ]
    Dose Escalation and Dose Expansion Phases

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Gender Based Eligibility: Yes
• Accepts Healthy Volunteers: No

Criteria

Key Inclusion Criteria:

mCRPC cohorts:

1. Men with histologically or cytologically confirmed adenocarcinoma of the prostate without pure small cell carcinoma.
2. Prostate specific antigen (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. post-177Lu-PSMA-617 radiotherapy expansion cohort only. Must have received at least 2 doses of 177Lu-PSMA-617.

ccRCC cohorts:

1. Men and women with 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 approved radiopharmaceutical therapy (eg. 177Lu-PSMA-617) in mCRPC patients
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 describe 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
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

Contacts and Locations

Contacts

Contact: Clinical Trials Administrator; 844-734-6643; clinicaltrials@regeneron.com

Locations

United States, Arizona

The University of Arizona Cancer Center; Recruiting

Tucson, Arizona, United States, 85724

United States, California

John Wayne Cancer Institute; Recruiting

Santa Monica, California, United States, 90404

United States, Colorado

Sarah Cannon Research Institute at HealthONE; Recruiting

Denver, Colorado, United States, 80218

United States, Connecticut

Yale University School of Medicine; Recruiting

New Haven, Connecticut, United States, 06520

United States, Florida

Moffitt Cancer Center; Recruiting

Tampa, Florida, United States, 33612

United States, Massachusetts

Massachusetts General Hospital; Recruiting

Boston, Massachusetts, United States, 02114

United States, New York

Laura & Isaac Perlmutter Cancer Center at NYU Langone Health; Recruiting

New York, New York, United States, 10016

Icahn School of Medicine at Mount Sinai; Recruiting

New York, New York, United States, 10029

Columbia University Medical Center; Recruiting

New York, New York, United States, 10032

Montefiore Medical Center; Recruiting

New York, New York, United States, 10461

United States, Oregon

Providence Cancer Institute Franz Clinic; Withdrawn

Portland, Oregon, United States, 97213

United States, Pennsylvania

Thomas Jefferson University, Sidney Kimmel Cancer Center, Clinical Research Organization; Recruiting

Philadelphia, Pennsylvania, United States, 19107

United States, Rhode Island

Rhode Island Hospital; Recruiting

Providence, Rhode Island, United States, 02903

United States, Texas

The University of Texas MD Anderson Cancer Center; Recruiting

Houston, Texas, United States, 77030

Sponsors and Collaborators

Regeneron Pharmaceuticals

Investigators

• Study Director: Clinical Trials Management; Regeneron Pharmaceuticals

More Information

• Responsible Party: Regeneron Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03972657
• Other Study ID Numbers: R5678-ONC-1879
• First Posted: June 3, 2019
• Last Update Posted: March 8, 2024
• Last Verified: March 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: All individual patient data (IPD) that underlie publicly available results will be considered for sharing
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code
• Time Frame: Individual anonymized participant data will be considered for sharing once the indication has been approved by a regulatory body, if there is legal authority to share the data and there is not a reasonable likelihood of participant re-identification.
• Access Criteria: Qualified researchers may request access to anonymized patient level data or aggregate study data when Regeneron has received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc) for the product and indication, has the legal authority to share the data, and has made the study results publicly available (eg, scientific publication, scientific conference, clinical trial registry).
• URL: https://vivli.org/

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Prostatic Neoplasms; Carcinoma, Renal Cell; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Kidney Neoplasms; Urologic Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Kidney Diseases; Urologic Diseases; Cemiplimab; Antineoplastic Agents, Immunological; Antineoplastic Agents