Clinical Summary: 

• Design/Population: Phase 2 study evaluating Convo-1α, an actinium-225–labeled PSMA-targeted radio-antibody conjugate, in 35 patients with metastatic castration-resistant prostate cancer previously treated with lutetium-177 PSMA radioligand therapy.
• Key Outcomes: Durable responses lasting 8 to 12 months were observed following only two fractionated doses, with limited xerostomia, no nephrotoxicity, and manageable hematologic toxicity. Activity was observed even among patients with lutetium-refractory disease.
• Clinical Relevance: These findings support further development of antibody-based alpha radioligand therapy as a potential treatment option for patients progressing after lutetium-based PSMA-targeted therapy.

Michael Morris, MD, Memorial Sloan Kettering Cancer Center, New York, New York, discusses phase 2 data evaluating Convo-1α, an investigational actinium-225 PSMA-targeted radio-antibody drug conjugate, in patients with metastatic castration-resistant prostate cancer previously treated with lutetium-177 PSMA therapy. Unlike peptide-based radioligands, Convo-1α uses an antibody platform designed to prolong tumor retention and radiation delivery while reducing uptake in the salivary glands and kidneys.

Among heavily pretreated patients, including those with primary or acquired resistance to lutetium-based therapy, Convo-1α demonstrated durable clinical activity after only two doses and maintained a favorable safety profile. These findings support continued phase 3 development and suggest that antibody-based alpha radioligand therapy may offer a differentiated approach for patients who have exhausted currently available PSMA-targeted treatments.

Dr Morris presented these results at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.

Transcript: 

Hi, my name is Michael Morris. I’m the prostate cancer section head at Memorial Sloan Kettering Cancer Center. I’m presenting at ASCO 2026 on a PSMA-directed radioligand therapy that is a little different from the current standard of care. Right now, the standard of care is lutetium-177–PSMA-617, which is a peptide, or small molecule, that targets PSMA. The drug I’m presenting is called Convo-1α. 

Convo-1α is an antibody, not a peptide, and it is radioconjugated with actinium-225 rather than lutetium-177, so it delivers an alpha-emitting payload. Because it is an antibody rather than a peptide, it has some potential advantages and some potential risks. For one thing, the antibody does not have the same salivary gland and lacrimal gland uptake that we see with the small-molecule PSMA-targeted agents. It also does not have the same renal uptake. By contrast, it does have hepatic and GI uptake. However, this drug has been studied in many patients through academic trials, and that has not translated into clinically significant hepatotoxicity, colitis, or related toxicities. With an antibody, we would anticipate less xerostomia, but potentially more hematologic toxicity because of the longer elimination half-life compared with a peptide.

On the other hand, there is also the potential for improved tumor retention and uptake because it is a larger molecule. It may become entrapped within tumors and continue delivering radiation at higher doses and for longer periods than a peptide. The study I’m discussing is a phase 2 trial of this agent. This drug was previously studied extensively at Weill Cornell Medicine in investigator-initiated studies led by Dr Scott Tagawa. Based on those studies, the optimal schedule was determined to be a fractionated dose delivered on day 1 and day 15. That schedule was brought forward into this trial—a single treatment course delivered as two fractionated doses separated by two weeks.

The patient population I’m discussing at ASCO is the subset of patients previously treated with lutetium-177 PSMA therapy. In other words, these are post-Pluvicto patients. Patients were required to have received at least one androgen receptor pathway inhibitor, no more than one chemotherapy regimen, and at least one but no more than six doses of lutetium-based therapy. These were therefore heavily pretreated patients. All had received at least one ARPI, approximately 80% had received chemotherapy, and all had received between one and six doses of lutetium.

Importantly, 8 patients were treated in the lutetium-refractory setting, meaning they had either primary refractory disease or rapidly developed resistance and had received fewer than four doses of lutetium. The remaining patients had received more than four doses. A total of 35 patients were treated in this portion of the study.

It’s also important to note, when interpreting toxicity data, that approximately half of the patients already had xerostomia either during or after prior treatment with lutetium-177. Specifically, 48.6% entered the study with xerostomia. When we looked at xerostomia after treatment, the rate was approximately 63%, representing an increase of about 14%. Of those patients, approximately 23% experienced grade 2 xerostomia, while the remainder had grade 1 toxicity. There were no cases of high-grade xerostomia and no nephrotoxicity. 

With regard to platelet counts, among patients treated at the dose selected for the upcoming phase 3 study, thrombocytopenia was generally grade 1 or less and not grade 2 or higher. There was grade 3 anemia observed, but there were no patients with grade 4 anemia and no patients who became transfusion-dependent.

In terms of durability, among patients treated at the target phase III dose or higher, responses lasting approximately 8 to 12 months were observed, despite patients receiving only two doses of therapy. Again, it is important to remember how heavily pretreated these patients were.

Looking ahead, the pre-chemotherapy, pre-Pluvicto cohort of this study continues to enroll. In addition, a phase 3 study in the post-Pluvicto, or post-radioligand therapy–exposed population, is currently being planned.

Source: 

Morris M, 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). Presented at the ASCO Annual Meeting. May 29 - June 2, 2026. Chicago, Illinois. Abstract 5011.