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

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

Overview

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

Interventions

• Drug REGN5678
  Administered as per the protocol
• Drug Cemiplimab
  Administered as per the protocol

Primary outcome measures

• Incidence and severity of Treatment-Emergent Adverse Events (TEAEs) [Time frame: Through study completion, up to 5 years]
• Incidence and severity of Adverse Event of Special Interests (AESIs) [Time frame: Through study completion, up to 5 years]
• Incidence and severity of Serious Adverse Events (SAEs) [Time frame: Through study completion, up to 5 years]
• Number of participants with Grade ≥3 laboratory abnormalities [Time frame: Through study completion, up to 5 years]
• Incidence of Dose-Limiting Toxicities (DLTs) [Time frame: First dose through day 42 of last participant in each dose level]
• Concentration of REGN5678 in serum over time [Time frame: Through study completion, up to 5 years]
• Concentration of REGN5678 in combination with cemiplimab in serum over time [Time frame: Through study completion, up to 5 years]
• Composite Response Rate (CRR) of 50% decline of Prostate Specific Antigen (PSA) and/or confirmed radiographic response of complete (CR) or partial response (PR) [Time frame: Through study completion, up to 5 years]
• Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria [Time frame: Through study completion, up to 5 years]

Secondary outcome measures (12)

• CRR of 50% decline of PSA and/or confirmed radiographic of CR or PR [Time frame: Through study completion, up to 5 years]
• ORR per RECIST 1.1 criteria [Time frame: Through study completion, up to 5 years]
• Incidence and severity of TEAEs [Time frame: Through study completion, up to 5 years]
• Incidence and severity of AESIs [Time frame: Through study completion, up to 5 years]
• Incidence and severity of SAEs [Time frame: Through study completion, up to 5 years]
• Number of participants with grade ≥3 laboratory abnormalities [Time frame: Through study completion, up to 5 years]
• Concentration of REGN5678 in serum over time [Time frame: Through study completion, up to 5 years]
• Concentration of REGN5678 in combination with cemiplimab in serum over time [Time frame: Through study completion, up to 5 years]
• Percentage of participants with ≥50% decline of PSA [Time frame: Through study completion, up to 5 years]
• Percentage of participants with ≥90% decline of PSA [Time frame: Through study completion, up to 5 years]
• Presence or absence of antibodies against REGN5678 [Time frame: Through study completion, up to 5 years]
• Presence or absence of antibodies against cemiplimab [Time frame: Through study completion, up to 5 years]

Eligibility criteria

Inclusion criteria

mCRPC cohorts (men):

• Men with histologically or cytologically confirmed adenocarcinoma of the prostate without pure small cell carcinoma.
• 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)
• 177Lu-PSMA-617 radiotherapy, or another lutetium-based PSMA targeted radioligand, as described in the protocol

ccRCC cohorts (men and women):

• 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

Exclusion criteria

• 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 a PSMA targeting radioligand (eg. 177Lu-PSMA-617) in mCRPC
• 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 described 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, as described in the protocol
• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 24 centers

• Banner MD Anderson Cancer Center — Gilbert
• Mayo Clinic — Phoenix
• University of Arizona — Tucson
• John Wayne Cancer Institute (JWCI) — Santa Monica
• Sarah Cannon Research Institute (SCRI) — Denver
• Yale University Hospital — New Haven
• Mayo Clinic Jacksonville — Jacksonville
• Moffitt Cancer Center - McKinley Drive — Tampa
• … and 16 more centers

Identifiers

NCT: NCT03972657 · R5678-ONC-1879

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗