This is a single-center, open-label, study of Prostate-Specific Membrane Antigen (PSMA)-targeted radionuclide therapy with 177Lu-PSMA-617 in combination with pembrolizumab in participants with metastatic castrate-resistant prostate cancer (mCRPC) who have previously progressed on at least one prior androgen pathway inhibitor (e.g., abiraterone, enzalutamide, apalutamide).
Male participants who are at least 18 years of age on the day of signing informed consent.
Histologically confirmed prostate adenocarcinoma that is progressive metastatic castration-resistant prostate cancer by Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria at the time of study entry.
Castrate level of serum testosterone at study entry (< 50 ng/dL). Note: Participants without prior bilateral orchiectomy are required to remain on Luteinizing hormone-releasing hormone (LHRH) analogue treatment for duration of study.
At least one Prostate-Specific Membrane Antigen (PSMA) Positron Emission Tomography (PET) (PSMA PET) avid lesion on screening PSMA PET. A positive lesion is defined as uptake above background liver.
De novo small cell neuroendocrine prostate cancer will not be allowed due to putative lower PSMA expression in this tumor subtype. Note-Treatment-emergent small cell neuroendocrine prostate cancer detected in metastatic tumor biopsy is not excluded.
Soft tissue lesions (lymph nodes > 1.5 centimeter (cm) in short axis, visceral/soft tissue lesions > 1 cm) on screening Computerized tomography (CT) that are negative on PSMA PET. Note: Negative lesions on PSMA PET are defined as those with uptake below the background liver.
Has received other systemic anti-cancer therapies administered within 14 days, or 5 half-lives, whichever is shorter, prior to initiation of study treatment. Note: LHRH analogues are the exception.
Untreated brain metastases at study entry.
Single group
Pembrolizumab
DrugGiven IV
177Lu-PSMA-617
DrugGiven IV
Median radiographic progression-free survival (rPFS) at 12 months
rPFS is defined as the amount of time from the initiation of study therapy and the day of first documented radiographic disease progression per RECIST version 1.1 and PCWG3 criteria. The proportion of patients without radiographic progression at 12 months from initiation of trial therapy will be reported along with the 95% confidence interval.
Overall median radiographic rPFS
rPFS is defined as the amount of time from initiation of study therapy until the participant experiences radiographic disease progression per RECIST v. 1.1 and PCWG3 criteria, initiates subsequent anti-cancer therapy, completes study participation, or experiences death from any cause (whichever is sooner). If disease progression or death from any cause is not observed prior to initiating subsequent anti-cancer therapy or completing study participation, the rPFS will be censored as the last available disease assessment. Participants who discontinue treatment for clinical progression or deterioration will be included in the analysis. Results will be reported in months
Objective response rate (ORR)
The proportion of participants treated with both 177Lu-PSMA-617 and Pembrolizumab who experience an objective response defined as a confirmed complete response (CR) or confirmed partial response (PR) per RECIST v. 1.1 and PCWG3 criteria from the initiation of trial therapy until confirmed response, disease progression, initiation of subsequent anti-cancer therapy, or participant has completed study participation (whichever occurs first). Point estimate of objective response rate will be obtained along with its 95% confidence interval.
Median duration of objective response (DOR)
Duration of objective response is defined as the amount of time between the day of first documented response to trial therapy (confirmed CR or confirmed PR, whichever is first recorded) and subsequent disease progression (per RECIST v. 1.1 and PCWG3 criteria). Median duration of objective response will be calculated based on the using Kaplan-Meier product limit method.
Proportion of participants with 50% decline in PSA (PSA50)
The proportion of participants who achieve greater than 50% decline in baseline PSA (drawn at the initiation of trial therapy), at any point during the course of treatment.
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University of California, San Francisco
Lead sponsor
Merck Sharp & Dohme LLC
Collaborator
Prostate Cancer Foundation
Collaborator
