Dr Enke on Interim Safety Data for Lutetium Lu 177 Vipivotide Tetraxetan Retreatment in mCRPC

“We had a predefined stopping threshold of 5 serious AEs [that were] treatment related in the trial. This [threshold] was not met, so we can continue the trial [within] safe limits.”

Johanna Enke, MD, a research physician with the Theranostics Clinical Research Program in the Department of Nuclear Medicine at UCLA Health, discussed interim safety data from the phase 2 Re-LuPSMA trial (NCT06288113) evaluating retreatment with lutetium Lu 177 vipivotide tetraxetan (Pluvicto) in patients with metastatic castration-resistant prostate cancer (mCRPC) who previously responded to the agent.

The findings were presented at the 2026 ESMO Congress. Re-LuPSMA is a single-center, single-arm, investigator-initiated study at UCLA enrolling patients who have received 4 to 6 cycles of lutetium Lu 177 vipivotide tetraxetan, achieved a prostate-specific antigen (PSA) decline of at least 50%, and later experienced disease progression, Enke explained. Eligible patients undergo PSMA PET imaging before receiving another course of the radioligand therapy, she said.

The trial protocol called for an interim safety analysis once half of the planned patients were enrolled, Enke noted. Of 20 patients enrolled, 19 received at least 1 dose of lutetium Lu 177 vipivotide tetraxetan. The median time from prior radioligand therapy to retreatment was 9.2 months (IQR, 5.8-19.7), and patients received a median of 3 retreatment cycles (IQR, 2-5).

Of 165 adverse effects (AEs) reported, 88 were considered possibly treatment related. The most common treatment-related AEs were lymphocytopenia (n = 14), leukopenia (n = 11), and anemia (n = 8).

The trial’s predefined stopping threshold of 5 or more treatment-related serious AEs was not reached, Enke said. Two cases of serious AEs, both anemia, were deemed treatment related and led to hospitalization, she added.

Looking ahead to additional updates in the field, Enke highlighted a randomized trial ongoing at UCLA, which is evaluating up to 12 cycles of lutetium Lu 177 vipivotide tetraxetan with the option of a treatment holiday for patients who respond well, such as those with a 90% PSA decline and reduced disease volume on imaging. This approach could extend the benefit of the agent, she said, noting that this portion of the study is enrolling.

She also highlighted the significance of the FDA’s July 2026 approval of lutetium Lu 177 vipivotide tetraxetan in combination with an androgen receptor pathway inhibitor for the treatment of patients with prostate-specific membrane antigen–positive metastatic hormone-sensitive prostate cancer.