The ever-evolving treatment landscape for metastatic castration-resistant prostate cancer (mCRPC) now increasingly includes novel radioligand therapies. At the 2026 ASCO Annual Meeting, emerging data focused on prostate-specific membrane antigen (PSMA)–targeted monoclonal antibody (mAb) radiopharmaceuticals. Looking forward, as efforts continue to identify novel radioligand therapies, there is a need to better understand tumor radiosensitivity to match patients based on individual tumor biology.

Following these presentations, featured expert Rana R. McKay, MD, FASCO, was interviewed by Conference Reporter Editor-in-Chief Tom Iarocci, MD. Clinical perspectives from Dr McKay on these findings are presented here.

Recently, tremendous progress has been made with regard to integrating radiopharmaceuticals into the treatment of prostate cancer. And I think that this has been built primarily off the foundation that was first established by radium-223, and now ¹⁷⁷Lu-PSMA-617. Treatment now warrants a multidisciplinary approach to ensure that patients have access to the right teams to ultimately administer the therapy. Because of this, things have become increasingly more complex; there are a lot of logistical challenges.

At ASCO 2026, Michael J. Morris, MD, FASCO, presented the phase 2 CONVERGE-01 clinical trial investigating ²²⁵Ac rosopatamab tetraxetan (CONV01-α) in patients with mCRPC who were previously treated with ¹⁷⁷Lu-PSMA-617 (abstract 5011). Eligible patients had previous exposure to at least 1 ARPI (with or without taxane exposure) and 1 to 6 cycles of ¹⁷⁷Lu-PSMA-617—so this was a heavily pretreated patient population. CONV01-α is an actinium-based alpha-emitting radionuclide that is conjugated to a PSMA-targeting mAb. This is a little bit different from ¹⁷⁷Lu-PSMA-617, which is a lutetium-based beta-emitting radionuclide that is conjugated to a PSMA-targeting small molecule. The phase 1 dose escalation study on the activity and safety of this agent in the context of various investigator-initiated trials was previously reported.

In the phase 2 trial, Dr Morris and colleagues reported that, across dose levels of 45 kBq/kg (DL45) and 55 kBq/kg (DL55), the most common high-grade treatment-emergent adverse events were largely hematologic and included lymphopenia, thrombocytopenia, and neutropenia. Among study participants at the lower dose level, lymphopenia and neutropenia were mostly low grade, and thrombocytopenia was all low grade. Xerostomia observed in the DL45 group was also low grade and mostly mild. When looking at the prostate-specific antigen (PSA) response rates among PSA-evaluable patients, 45.4% achieved a PSA decline of 50% or greater at DL45, which was the dose level identified as the recommended phase 2 dose for expansion.

We also saw preliminary data from part 1 of the phase 3 ProstACT Global study of ¹⁷⁷Lu-rosopatamab tetraxetan plus standard of care in patients with mCRPC at ASCO 2026, which were presented by Pedro Barata, MD, MSc, FACP (abstract LBA5009). This agent is a lutetium-based beta-emitting radionuclide that is conjugated to a PSMA-targeting mAb. Here, data from 36 patients who had received any study treatment were included; 25% had received a prior taxane, and 72% had received 2 prior lines of therapy for mCRPC.

The predominant treatment-emergent adverse events were mostly hematologic and included thrombocytopenia, neutropenia, and lymphopenia. For thrombocytopenia, 77.8% of patients experienced any grade and 44.4% experienced grade 3 or higher; for neutropenia, 63.9% experienced any grade and 47.2% experienced grade 3 or higher; and for lymphopenia, 55.6% experienced any grade and 41.7% experienced grade 3 or higher. Nonhematologic toxicities included xerostomia, which was reported in 25% of patients and were all grade 1 events. Overall, I think that this is a manageable safety tolerability profile with predictable pharmacokinetics, and this supports the continued investigation of ¹⁷⁷Lu-rosopatamab tetraxetan with randomized treatment expansion in part 2 of the trial, which is actively recruiting participants.

Another presentation at this year’s ASCO meeting that is worth mentioning is titled “Innovation in Radiopharmaceutical Technology, Targets, and Treatment Delivery to Enhance Safety and Effectiveness,” which was presented by Lisa Bodei, MD, PhD, during an education session. Here, Dr Bodei covered the complex factors involved in radiosensitivity.

Of course, to get a treatment response, the tumor has to be sensitive to the radiopharmaceutical. And hopefully there is more work to come on this—to get beyond just imaging and mean standardized uptake value to understanding on a molecular level not only where the target is but also how sensitive the target is to radiopharmaceutical treatment. PSMA positron emission tomography/computed tomography scans tell us where the target is, but you could have a tumor that is expressing PSMA that is quite resistant to the DNA damage incurred by radiation therapy. So, I think this is something that is going to evolve. The beauty of an alpha particle is that the energy source or the energy emitted is quite high and elicits a great degree of DNA damage that could potentially overcome some of that. However, we still need to better understand what is going on with these tumors at a molecular level.