CONV01-α (Ac-225 PSMA–mAb alpha-radioconjugate) drives 45% PSA50 in Lu-PSMA–pretreated mCRPC

Ac-225 rosopatamab tetraxetan (CONV01-α) is an actinium-225 alpha-emitting radionuclide conjugated to a PSMA-targeting monoclonal antibody, evaluated in the Phase 2 CONVERGE-01 Part 3 dose-escalation/initial expansion study in PSMA PET–positive (VISION criteria) mCRPC previously treated with ≥1 ARPI, 0-1 taxane regimens, and 1-6 cycles of Lu-PSMA (NCT06549465). In 22 treated patients (DL45 n=12; DL55 n=10; 21/22 taxane-exposed, mostly in the CRPC setting), no DLTs were seen; at DL45, thrombocytopenia was mostly grade 1-2 (5/12) and xerostomia was limited to grade 1-2 (6/12), while Grade ≥3 TEAEs across cohorts included lymphopenia 36%, thrombocytopenia 23% (notably 50% at DL55), neutropenia 18%, and anemia 14%. Among PSA-evaluable patients at DL45, 45.4% achieved PSA50 (5/11), leading DL45 (45 kBq/kg; two doses on D1 and D15) to be selected as RP2D—numerically in the ballpark of cabazitaxel PSA50 rates in post-docetaxel mCRPC (~37% in TheraP), but here in a more treatment-exhausted post–Lu-PSMA population where benchmarks are generally lower and cross-trial comparisons are shaky.