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

Overview

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

Full Title of Study: “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”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Non-Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: August 1, 2025

Interventions

  • 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

Arms, Groups and Cohorts

  • 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.
  • Experimental: mCRPC – dose expansion cohort
    • Participants will receive the REGN5678 presumptive RP2D(s)
  • 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.
  • Experimental: ccRCC – dose expansion cohort
    • Participants will receive the REGN5678 presumptive RP2D(s)

Clinical Trial Outcome Measures

Primary Measures

  • Incidence and severity of treatment-emergent adverse events (TEAEs)
    • Time Frame: Through study completion, Up to 5 years
    • Dose Escalation Phase
  • Incidence and severity of adverse event of special interests (AESIs)
    • Time Frame: Through study completion, Up to 5 years
    • Dose Escalation Phase
  • Incidence and severity of serious adverse events (SAEs)
    • Time Frame: Through study completion, Up to 5 years
    • Dose Escalation Phase
  • Number of participants with Grade ≥3 laboratory abnormalities
    • Time Frame: Through study completion, Up to 5 years
    • Dose Escalation Phase
  • Incidence of dose-limiting toxicities (DLTs)
    • Time Frame: First dose through day 42 of last participant in each dose level
    • Dose Escalation Phase
  • Concentration of REGN5678 in serum over time
    • Time Frame: Through study completion, Up to 5 years
    • Dose Escalation Phase
  • Concentration of REGN5678 in combination with cemiplimab in serum over time
    • Time Frame: Through study completion, Up to 5 years
    • Dose Escalation Phase
  • 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
  • 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 Measures

  • ORR per modified PCWG3 criteria
    • Time Frame: Through study completion, Up to 5 years
    • Dose Escalation Phase – mCRPC cohort
  • ORR per RECIST 1.1 criteria
    • Time Frame: Through study completion, Up to 5 years
    • Dose Escalation Phase – ccRCC cohort
  • Incidence and severity of TEAEs
    • Time Frame: Through study completion, Up to 5 years
    • Dose Expansion Phase
  • Incidence and severity of AESIs
    • Time Frame: Through study completion, Up to 5 years
    • Dose Expansion Phase
  • Incidence and severity of SAEs
    • Time Frame: Through study completion, Up to 5 years
    • Dose Expansion Phase
  • Number of participants with grade ≥3 laboratory abnormalities
    • Time Frame: Through study completion, Up to 5 years
    • Dose Expansion Phase
  • Concentration of REGN5678 in serum over time
    • Time Frame: Through study completion, Up to 5 years
    • Dose Expansion Phase
  • Concentration of REGN5678 in combination with cemiplimab in serum over time
    • Time Frame: Through study completion, Up to 5 years
    • Dose Expansion Phase
  • 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
  • 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
  • Presence or absence of antibodies against REGN5678
    • Time Frame: Through study completion, Up to 5 years
    • Dose Escalation and Dose Expansion Phases
  • Presence or absence of antibodies against cemiplimab
    • Time Frame: Through study completion, Up to 5 years
    • Dose Escalation and Dose Expansion Phases

Participating in This Clinical Trial

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

Gender Eligibility: Male

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Regeneron Pharmaceuticals
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Clinical Trials Management, Study Director, Regeneron Pharmaceuticals
  • Overall Contact(s)
    • Clinical Trials Administrator, 844-734-6643, clinicaltrials@regeneron.com

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.