Ac-225 rosopatamab tetraxetan shows promising activity in Lu-PSMA–pretreated mCRPC

Actinium-225 (Ac-225) rosopatamab tetraxetan (CONV01-α) demonstrated encouraging antitumor activity with a manageable safety profile in patients with metastatic castration-resistant prostate cancer (mCRPC) whose disease progressed after prior lutetium-177 (Lu-177)-PSMA radioligand therapy, according to interim results from the phase 2 CONVERGE-01 trial.

CONV01-α combines a humanized monoclonal antibody directed against prostate-specific membrane antigen (PSMA) with the alpha-emitting radionuclide actinium-225. The findings on the agent were presented by Michael J. Morris, MD, during the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.

"These data are encouraging as CONVERGE-01 demonstrates meaningful antitumor activity and emerging durability in patients who have already received Lu-PSMA therapy. These data are striking given that the regimen is comprised of only 2 treatments, and a reduced treatment burden is important in this very advanced population,” said Morris, who is the CONVERGE-01 study Scientific Advisory Committee Co-Chair and medical oncologist at Memorial Sloan Kettering Cancer Center, in a news release on the data.² “The safety profile observed in CONVERGE-01 shows manageable hematologic toxicity, and no renal toxicity or high-grade xerostomia.”

About the CONVERGE-01 trial

The multicenter, open-label phase 2 CONVERGE-01 trial (NCT06549465) enrolled patients with progressive PSMA-positive mCRPC previously treated with Lu-177-PSMA radioligand therapy. Eligible patients had received at least 1 androgen receptor pathway inhibitor (ARPI), no more than 1 prior taxane regimen, and between 1 and 6 prior doses of Lu-177-PSMA therapy.

In the phase 2 cohort presented at ASCO, 35 patients received fractionated treatment on days 1 and 15. Investigators reported that 80% had previously received taxane chemotherapy, all had received ARPI therapy, and the median number of prior Lu-177-PSMA treatment cycles was 6 (range 2 to 6). The median follow-up at the time of analysis was 8.14 months.

Among 25 patients evaluable for prostate-specific antigen (PSA) response, 40% achieved a PSA decline of at least 50%, with responses observed across dose groups (above, below, or on target with the target dose). Investigators noted that durability appeared greatest at the intended phase 3 target dose (9 MBq), with median radiographic progression-free survival reaching 8.41 months (95% CI, 2.83 to inf) in this group.

According to Morris, treatment with CONV01-α was well-tolerated. Grade 3 treatment-emergent adverse events (TEAEs) were clinically manageable and generally transient. No treatment-related adverse events led to treatment discontinuation. The most common TEAEs included dry mouth (62.9%), nausea (60%), decrease lymphocyte count (60%), decrease platelet count (60%), fatigue (54.3%), anemia (40%), decrease appetite (40%), decreased white blood cell count (40%), decrease neutrophil count (34.3%), and dysgeusia (22.9%).

Notably, 48.6% of enrolled patients had baseline xerostomia related to prior radioligand therapy, which increased to 62.9% during treatment. No grade 3 or higher xerostomia was reported.

“I do find the xerostomia quite interesting, because on the distribution studies, there really is not very much in the way of salivary gland uptake,” Morris noted during the presentation. “Yet there must have been some additional exposure to tick the xerostomia rate up by 14 points.”

CONVERGE-01 continues to enroll taxane- and Lu-PSMA-naïve patients. Convergent Therapeutics also plans to initiate a pivotal phase 3 trial in patients with prior Lu-PSMA therapy.

Morris concluded, “These data support the continued evaluation of this PSMA-targeted alpha radioantibody approach in the Lu-PSMA-exposed setting."

REFERENCES

1. Morris MJ, George DJ, Gupta S, et al. CONVERGE-01 part 3: Ac-225 rosopatamab tetraxetan (CONV01-α) in Lu-PSMA-pretreated metastatic castration-resistant prostate cancer (mCRPC). J Clin Oncol. 44, 2026 (suppl 16; abstr 5011). doi:10.1200/JCO.2026.44.16_suppl.5011

2. Convergent Therapeutics Announces Positive Phase 2 Data at ASCO 2026 Showing Promising Anti-Tumor Activity, Durability, and Favorable Tolerability for CONV01-α in Lu-PSMA-Exposed Metastatic Castration-Resistant Prostate Cancer (mCRPC). News release. Convergent Therapeutics. June 1, 2026. Accessed June 29, 2026. https://www.businesswire.com/news/home/20260601939715/en/Convergent-Therapeutics-Announces-Positive-Phase-2-Data-at-ASCO-2026-Showing-Promising-Anti-Tumor-Activity-Durability-and-Favorable-Tolerability-for-CONV01--in-Lu-PSMA-Exposed-Metastatic-Castration-Resistant-Prostate-Cancer-mCRPC