177Lu-PSMA-617 With Liver Directed Therapy in Metastatic Castration Resistant Prostate Cancer

PRIMARY OBJECTIVES:

I. To characterize the safety profile of 177Lu-PSMA-617 in combination with liver-directed therapy.

II. To determine the investigator-assessed objective response rate per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria in patients with mCRPC treated with 177LuPSMA-617 and liver-directed therapy.

SECONDARY OBJECTIVES:

I. To determine the median radiographic progression-free survival per PCWG3 criteria in patients with mCRPC treated with 177Lu-PSMA-617 and liver-directed therapy.

II. To determine the median overall survival in patients with mCRPC treated with 177Lu-PSMA-617 and liver-directed therapy.

III. To determine the median investigator-assessed duration of objective response per RECIST 1.1 criteria in patients with mCRPC treated with 177Lu-PSMA-617 and liver-directed therapy.

IV. To determine the investigator-assessed hepatic disease response rate (HDRR) per RECIST 1.1 in patients with mCRPC treated with 177Lu-PSMA-617 and liver-directed therapy.

V. To determine the investigator-assessed hepatic disease control rate (HDCR) at 6 months per RECIST 1.1 in patients with mCRPC treated with 177Lu-PSMA-617 and liver-directed therapy.

VI. To determine the PSA response rate by Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria for participants with 50% decline (PSA50) and participants with a 90% decline (PSA90) at any time point on study, as well as individually following each dose of 177Lu-PSMA-617 or liver-directed therapy.

OUTLINE:

Participants will receive treatment with 177Lu-PSMA-617 for up to six total cycles every 6 weeks. Participants with one or more PSMA-negative liver lesions with a single session of liver-directed therapy prior to initiation of study drug. Participants will be follow-up every 3 months up to 5 years after the last study treatment.