CONVERGE-01: CONV01-α Shows Activity After Lu-PSMA in mCRPC

Actinium-225 rosopatamab tetraxetan (CONV01-α) is a PSMA-targeted alpha radioligand therapy being tested in men with metastatic castration-resistant prostate cancer who have already received androgen receptor pathway inhibitors, up to one taxane regimen, and 1–6 cycles of lutetium-177 PSMA therapy (Pluvicto), with all patients having PSMA PET–positive disease by VISION criteria. The drug links an alpha emitter (Ac-225) to a PSMA-targeting monoclonal antibody, giving it different pharmacokinetics and tissue distribution compared with other Lu-PSMA agents, and potentially enabling more potent, highly localized DNA damage to PSMA-expressing cells.

In the CONVERGE-01 phase 2 trial, CONV01-α is given as a single cycle of two doses on day 1 and day 15 using a Bayesian optimal interval design for dose escalation. Dose escalation was completed without dose-limiting toxicities, and an initial expansion brought the total to 22 patients. Grade1-2 thrombocytopenia occurred in 5 of 12 patients, and dry mouth was limited to grade 1–2 in six patients, suggesting a manageable safety profile for an Ac-225 PSMA therapy in this setting.

Among patients treated at 45 kBq/kg who were evaluable for prostate-specific antigen response, 45.4 percent (5 of 11) achieved at least a 50 percent PSA decline, with some experiencing ongoing PSA reductions at the time of analysis, including patients who had been primarily refractory to prior lutetium-177 PSMA therapy.

Based on the absence of dose-limiting toxicities, manageable hematologic and salivary toxicity, and this level of PSA response in a heavily pretreated Lu-PSMA–exposed population, 45 kBq/kg was selected as the recommended dose, and further expansion and a planned pivotal study are underway.

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