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

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

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

Study Overview

• Status: Recruiting
• Conditions: Metastatic Castration-resistant Prostate Cancer (mCRPC); Clear Cell Renal Cell Carcinoma (ccRCC)
• Intervention / Treatment: Drug: REGN5678; Drug: Cemiplimab

• Study Type: Interventional
• Enrollment (Estimated): 345
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Clinical Trials Administrator; Phone Number: 844-734-6643; Email: clinicaltrials@regeneron.com

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • Recruiting
      • The University of Arizona Cancer Center
  • California
    • Santa Monica, California, United States, 90404
      • Recruiting
      • John Wayne Cancer Institute
  • Colorado
    • Denver, Colorado, United States, 80218
      • Recruiting
      • Sarah Cannon Research Institute at HealthONE
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Recruiting
      • Yale University School of Medicine
  • Florida
    • Tampa, Florida, United States, 33612
      • Recruiting
      • Moffitt Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
  • New York
    • New York, New York, United States, 10029
      • Recruiting
      • Icahn School of Medicine at Mount Sinai
    • New York, New York, United States, 10016
      • Recruiting
      • Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Medical Center
    • New York, New York, United States, 10461
      • Recruiting
      • Montefiore Medical Center
  • Oregon
    • Portland, Oregon, United States, 97213
      • Withdrawn
      • Providence Cancer Institute Franz Clinic
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Recruiting
      • Thomas Jefferson University, Sidney Kimmel Cancer Center, Clinical Research Organization
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Recruiting
      • Rhode Island Hospital
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • The University of Texas MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Investigators: Study Director: Clinical Trials Management, Regeneron Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): August 12, 2019
• Primary Completion (Estimated): August 1, 2025
• Study Completion (Estimated): July 3, 2026

Study Registration Dates

• First Submitted: May 30, 2019
• First Submitted That Met QC Criteria: May 30, 2019
• First Posted (Actual): June 3, 2019

Study Record Updates

• Last Update Posted (Actual): March 8, 2024
• Last Update Submitted That Met QC Criteria: March 5, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Male; Prostatic Diseases; Kidney Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Carcinoma, Renal Cell; Prostatic Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Cemiplimab
• Other Study ID Numbers: R5678-ONC-1879; 2022-502131-19-00 (Other Identifier: EUCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All individual patient data (IPD) that underlie publicly available results will be considered for sharing
• IPD Sharing 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.
• IPD Sharing 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).
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No