Dr Morris on Notable Ongoing Research in Prostate Cancer

“There's an ongoing randomized study looking at [lutetium Lu 177 vipivotide tetraxetan] one step earlier than PSMAddition in patients with oligometastatic disease who are PSMA-avid, and that trial, [the phase 3 PSMA-DC study], eliminates ADT altogether.”

Michael J. Morris, MD, the prostate cancer section head of genitourinary oncology and the Steven A. Greenberg Chair in Prostate Cancer Research at Memorial Sloan Kettering Cancer Center, discussed ongoing studies of lutetium Lu 177 vipivotide tetraxetan (Pluvicto) and other agents in prostate cancer.

The development of prostate cancer theranostics is rapidly expanding beyond the current use of lutetium Lu 177 vipivotide tetraxetan, with multiple approaches being evaluated across earlier disease settings and new molecular targets, Morris began. One ongoing randomized phase 3 study, PSMA-DC (NCT05939414), is investigating lutetium Lu 177 vipivotide tetraxetan in an earlier treatment setting than the phase 3 PSMAAddition trial (NCT04720157). The trial is enrolling patients with PSMA-avid oligometastatic prostate cancer and is evaluating stereotactic body radiation therapy with or without lutetium Lu 177 vipivotide tetraxetan, he explained. Notably, the study eliminates androgen deprivation therapy, potentially providing important insight into whether targeted radioligand therapy can contribute to disease control without concurrent hormonal therapy, he added.

Beyond lutetium Lu 177 vipivotide tetraxetan, several next-generation theranostic strategies are advancing through clinical development, Morris emphasized. Actinium-PSMA–directed therapies are among the most mature approaches, with multiple randomized phase 3 registration trials underway in metastatic castration-resistant prostate cancer, he said. These studies are evaluating actinium-based therapy in both the post-lutetium and pre-lutetium settings, potentially establishing a role for alpha-emitting radiopharmaceuticals at different points in the treatment sequence, he said.

Other alpha-emitting approaches are also being investigated. Early studies evaluating lead-212–based therapies are progressing, with future data expected to help clarify how these agents compare with actinium-based treatments, Morris noted. Because alpha emitters can deliver highly potent radiation over a short range, these therapies represent another avenue for advancing targeted radiopharmaceutical treatment, he said.

The theranostic field is also expanding beyond PSMA as investigators explore new molecular targets, Morris said. ACP3, B7-H3, and STEAP2 have emerged as promising targets for next-generation therapies, although these approaches remain at earlier stages of development compared with actinium-PSMA agents, he concluded.