CONVERGE-01 part 3: Ac-225 rosopatamab tetraxetan (CONV01-α) in Lu-PSMA-pretreated metastatic castration-resistant prostate cancer (mCRPC).

5011 Background: Ac-225 rosopatamab tetraxetan (CONV01-α, Convergent Therapeutics, Cambridge, MA), an alpha-emitting radionuclide conjugated to a PSMA-targeting monoclonal antibody, has demonstrated safety and encouraging activity in prior investigator-initiated trials (Tagawa et al. JCO 2024, Nauseef et al. AACR 2023). This phase 2 Convergent Therapeutics-sponsored multi-center CONVERGE-01 trial is evaluating the safety and efficacy of CONV01-α in pts with mCRPC, including those previously treated with Lu-PSMA-617 or -I&T (Lu-PSMA), in a dose-escalation (DE) and in an Initial Expansion (IE) cohort. Methods: Eligible pts had PSMA PET-positive (VISION criteria) mCRPC with previous exposure to ≥1 ARPI, 0-1 taxane regimens, and 1-6 cycles of Lu-PSMA. CONV01-α was administered in a single cycle of two doses (D1 & D15). Dose escalation used a BOIN design protocol (dose levels [DLs]: 45 and 55 kBq/kg, with optional IE). Primary endpoints: safety (CTCAE v5, all pts) and proportion of patients with decline in PSA of 50% or greater (PSA50) (at recommended phase 2 dose [RP2D]). Secondary endpoints: biodistribution and pharmacokinetic profile. Exploratory endpoints: bPFS, rPFS, genomic and imaging biomarkers. Enrollment into DE and IE cohorts of Part 3 was conducted between 8/2024 and 12/2025. Data within reflect current status and are subject to change with continued follow up and analysis. Results: DE was completed without DLTs in all evaluable pts (n=3 at DL45, n=6 at DL55). This was followed by an IE at both DLs (total n=22, incl pts in DE; DL45: n=12, DL55: n=10). ECOG: PS 0 - 12/22, PS 1 - 10/22. 21/22 pts were taxane exposed (19 for CRPC). Common grade (Gr) ≥3 treatment emergent adverse events (TEAEs) (occurring in >1 pt) are in shown Table. Among all TEAE at DL45: thrombocytopenia occurred in 5/12 patients (Gr 1 3/12, Gr 2 2/12), without clinical sequelae. Dry mouth was limited to Gr 1 (5/12) and Gr 2 (1/12). Among pts at who were evaluable for PSA change, 45.4% (5/11) achieved a PSA50 at DL45, with several pts experiencing ongoing PSA declines including pts who were primarily refractory to Lu-PSMA. Based on the combined safety and activity profile, DL45 was chosen as RP2D and Subsequent Expansion is underway. Conclusions: CONV01-α at the RP2D of DL45 is well-tolerated and shows promising activity in a heavily pretreated and Lu-PSMA-exposed population where there are limited therapeutic options available. Subsequent Expansion continues for pts exposed to Lu-PSMA (Part 3) at RP2D of DL45. A pivotal study is planned. Clinical trial information: NCT06549465 . Grade ≥3 TEAE. Overall n=22 DL45Grade 3 DL45Grade 4 DL55Grade 3 DL55Grade 4 n (%) n (%) n (%) n (%) n (%) Lymphopenia 8 (36) 3 (25) 0 3 (30) 2 (20) Thrombocytopenia 5 (23) 0 0 5 (50) 0 Neutropenia 4 (18) 2 (16) 0 2 (20) 0 Anemia 3 (14) 1 (8) 0 2 (20) 0 Hypotension 2 (9) 1 (8) 0 1 (10) 0