Phase 3 177Lu vipivotide tetraxetan PSMA-targeted beta-emitting radioligand with adaptive dosing (RECIPROCAL)

Alliance for Clinical Trials in Oncology’s RECIPROCAL (A032304; NCT07200830) is a randomized Phase 3 strategy trial asking whether when to give additional doses of 177Lu vipivotide tetraxetan (Novartis’ PSMA-targeted radioligand therapy; a small molecule that binds PSMA and delivers beta-particle radiation) can be individualized without sacrificing survival. Everyone first receives two standard 6‑week–spaced doses; only patients who achieve an initial PSA50 response after cycle 2 proceed to randomization. Step 1 compares continued fixed q6‑week dosing (up to 4 more cycles) vs an adaptive approach that delays subsequent doses until biochemical/clinical evidence of renewed disease activity, with close PSA monitoring every 3 weeks. The commercial/scientific angle is “response-adapted radioligand scheduling” in a setting where the drug is active but cumulative hematologic toxicity and treatment burden matter. For progressive mCRPC on ongoing androgen deprivation (or after orchiectomy), today’s care typically layers androgen receptor pathway inhibitors, taxane chemotherapy, PARP inhibitors for HRR-altered tumors, immunotherapy for MSI‑H/TMB‑high disease, and PSMA radioligand therapy in eligible PSMA‑PET–positive patients—this trial tests whether a less-intensive maintenance pattern can preserve overall survival while improving quality of life.