Perlmutter Cancer Center

This is an open-label, phase 1/2, first-in-human (FIH) study evaluating safety, tolerability, PK, and anti-tumor activity of REGN5678 (anti- PSMAxCD28) alone and in combination with cemiplimab (anti-PD-1) in treatment-experienced metastatic castration-resistant prostate cancer (mCRPC). There are two parts of the study: ? Dose escalation: During dose escalation, patients will receive a 3- week monotherapy lead-in of REGN5678 at the assigned dose level (DL) administered intravenously (IV) weekly (QW) followed by combination therapy of REGN5678 at the assigned DL IV QW and cemiplimab 350 mg IV every 3 weeks (Q3W). ? Dose Expansion: During dose expansion, patients will receive combination therapy of REGN5678 at the assigned DL (eg, maximum tolerated dose [MTD]/recommended phase 2 dose [RP2D]) IV QW and cemiplimab 350 mg IV Q3W without a 3- week monotherapy lead-in of REGN5678. Dose expansion cohort(s) will be enrolled after identification of the REGN5678 MTD in combination with cemiplimab and/or RP2D. Prior to enrollment of an expansion cohort, 3 to 6 additional patients will be enrolled at that DL without a 3-week monotherapy lead-in of REGN5678 to further evaluate safety and biologic activity (dose escalation cohorts designated with an asterisk [*cohorts]). Safety evaluations will be conducted at each study drug dosing visit. Radiographic response assessment will be performed every 6 weeks from cycle 1 (C1D42/C2D1) up to cycle 4 (including patients who receive the initial 3-week monotherapy lead-in of REGN5678) and every 12 weeks thereafter. Investigators should continue treating patients with study drug until confirmed disease progression, elective discontinuation for response, per modified PCWG3, intolerable adverse events (AEs), withdrawal of consent, or other study withdrawal criterion is met. Patients who do not withdraw consent will then be expected to continue off-treatment follow-up procedures.