Lu-177-PSMA Retreatment Clears Interim Safety Bar in mCRPC

Retreatment with lutetium Lu-177 vipivotide tetraxetan (Pluvicto) did not exceed a predefined safety stopping threshold in patients with metastatic castration-resistant prostate cancer (mCRPC) who previously responded to prostate-specific membrane antigen (PSMA)–targeted radioligand therapy, according to a poster presented by Johanna S. Enke, MD, of the Theranostics Clinical Research Program at UCLA Health at the 2026 European Society for Medical Oncology (ESMO) Congress.

According to Enke, the phase 2, single-arm, investigator-initiated Re-LuPSMA trial (NCT06288113) at UCLA, is evaluating up to 6 retreatment cycles. Eligible patients achieved a prostate-specific antigen decline of at least 50% during initial therapy, and PSMA PET confirmed their eligibility for retreatment. The prespecified interim analysis included the first 20 of 40 planned patients. Of these, 19 received at least 1 dose, with a median of 3 retreatment cycles (IQR, 2-5).

Of 148 adverse events (AEs) recorded, 74 were considered possibly treatment related (TR), including 8 grade 3 and 4 grade 4 events. The most common TRAEs were leukopenia (n = 12), anemia (n = 10), thrombocytopenia (n = 10), and xerostomia (n = 10). Two serious AEs, grade 3 and grade 4 anemia requiring hospitalization, were deemed possibly treatment related. This was below the protocol’s stopping criterion of 5 serious TRAEs. No treatment-related deaths occurred, and 3 grade 5 events were attributed to disease progression.

Enke noted that hematologic AEs are common in heavily pretreated patients, whose disease progression can also lower blood counts. The efficacy data are not yet available, but Enke said the findings support continued study to learn if additional treatment will help patients maintain stable disease. Enrollment is on track to reach 40 patients, after which the primary and secondary end points will be analyzed.

Enke said she is looking forward to the efficacy data to give these patients an alternative to other treatments, and it is especially notable as lutetium Lu-177 vipivotide tetraxetan moves to earlier prostate cancer treatment settings and as other therapies become available for mCRPC.

REFERENCE

Enke JS, Kimura K, Theus L, et al. Interim safety analysis of the prospective phase II trial of [177Lu]Lu-PSMA-617 retreatment in metastatic castration-resistant prostate cancer. Presented at: 2026 ESMO Congress; October 23-27, 2026; Madrid, Spain. Abstract 2246P.