Study of REGN5678 (Anti-PSMAxCD28) With or Without Cemiplimab (Anti-PD-1) in Patients With Metastatic Castration-resistant Prostate Cancer and Other Tumors

Study of REGN5678 (Anti-PSMAxCD28) With or Without Cemiplimab (Anti-PD-1) in Patients 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 of REGN5678 with or without cemiplimab. There are additional purposes of this study including measurement of the levels of REGN5678 in your blood when given alone and when given in combination with cemiplimab, and collection of any evidence of tumor shrinkage. The study has 2 parts. The goal of Part 1 is to determine a safe dose(s) of REGN5678 when it is given alone and then followed by combination with cemiplimab. The goal of Part 2 of the study 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. Note: All the above primary, secondary objectives will apply to each cohort (unless specified) in the study including those who receive sarilumab and those who do not receive sarilumab.

Participants will receive monotherapy lead-in of REGN5678 followed by a combination of REGN5678 and cemiplimab, with or without sarilumab prophylaxis.

Participants will receive either REGN5678 monotherapy or combination therapy of REGN5678 (with or without a monotherapy lead-in) at the recommended phase 2 dose (RP2D) and cemiplimab for mCRPC. Expansion cohorts may be performed in cohorts with or without sarilumab and participants with mCRPC that have received prior received prostate-specific membrane antigen (PSMA)-targeted lutetium Lu 177 vipivotide tetraxetan radiotherapy (177Lu-PSMA-617).

Participants will receive REGN5678 in combination therapy of REGN5678 at the MTD/presumptive RP2D(s) and cemiplimab. Expansion cohorts may be performed in cohorts with or without sarilumab.

Administered at the assigned dose level (DL) by intravenous (IV) infusion or subcutaneous (SC) administration

Percentage of participants who have achieved conversion of circulating tumor cell (CTC) count from baseline of ≥5 cells/7.5mL to <5 cells/7.5mL

Key Inclusion Criteria: Histologically or cytologically confirmed adenocarcinoma of the prostate without pure small cell carcinoma (mCRPC cohorts). Metastatic, castration-resistant prostate cancer (mCRPC) with PSA value at screening ≥4 ng/mL that has progressed within 6 months prior to screening as defined in the protocol (mCRPC cohorts). (mCRPC cohorts) 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) Has received at least 2 doses of 177Lu-PSMA-617. Prior therapy 177Lu-PSMA-617 is not permitted in other cohorts 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 Tumor PSMA expression via PSMA-positron emission tomography (PET), as defined by at least one PSMA-PET positive lesion with signal above liver background via visual assessment per central review 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: 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 Has received any previous systemic biologic therapy within 5 half-lives of first dose of study therapy Has received prior PSMA-targeting therapy Dose Expansion (mCRPC only): Has had prior anti-cancer immunotherapy 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 - At this time, we are only enrolling the REGN5678 monotherapy expansion cohort

All individual patient data (IPD) that underlie publicly available results will be considered for sharing

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.

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).