Pembrolizumab Plus 177Lu-PSMA-617 in Patients With Castration Resistant Prostate Cancer

Description

PRIMARY OBJECTIVE:

I. To determine the 12-month radiographic progression-free survival rate per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria in patients with mCRPC treated with pembrolizumab and 177Lu-PSMA-617.

SECONDARY OBJECTIVES:

I. To determine the median radiographic progression-free survival per RECIST v. 1.1 and PCWG3 criteria in patients with mCRPC treated with pembrolizumab and 177Lu-PSMA-617.

II. To determine the objective response rate per RECIST v. 1.1 and PCWG3 criteria in patients with mCRPC treated with pembrolizumab and 177Lu-PSMA-617.

III. To determine the median duration of objective response per RECIST v. 1.1 and PCWG3 criteria in patients with mCRPC treated with pembrolizumab and 177Lu-PSMA-617.

IV. To determine the greater than 50% decline from baseline PSA (PSA50) and greater than 90% decline from baseline PSA (PSA90) response rate by PCWG3 criteria at any time point on study, as well as individually following each dose of 177Lu-PSMA-617.

V. To determine the median time to PSA progression (TTPP) following each dose of 177Lu-PSMA-617 (e.g., TTPP-1, TTPP-2, etc.), as measured by PCWG3 criteria.

VI. To determine the median overall survival in patients with mCRPC treated with pembrolizumab and 177Lu-PSMA-617.

VII. To characterize the safety profile of the combination of pembrolizumab and 177Lu-PSMA-617 in patients with mCRPC.

EXPLORATORY OBJECTIVES:

I. To determine the lesion-specific response by baseline uptake on PSMA PET.

II. To determine the patterns of PSMA expression at the time of each TTPP event and at radiographic progression.

III. To further characterize the tumor microenvironment using Single-cell RNA sequencing (scRNA-seq) of paired metastatic tumor biopsies (a biopsy is required if there is an accessible lesion).

IV. To develop a biomarker predictive of durable response based on Cytometry by time of flight (CyTOF) profiling of whole blood samples collected at baseline and early time points on treatment.

V. To determine whether successive doses of 177Lu-PSMA-617 leads to ablation of effector T cells and up- regulation of myeloid cell states in the periphery and tumor microenvironment.

VI. To characterize participant reported outcomes using the Brief Pain Inventory and The Functional Assessment of Cancer Therapy – Prostate (FACT-P) instruments.

VII. To correlate the number of 177Lu-PSMA-617 re-priming doses and PSA progression events with radiographic rPFS.

VIII. To evaluate and compare the efficacy of 177Lu-PSMA-617 between the subgroup of participants who received a single dose of 177Lu-PSMA-617 followed by adaptive dosing, and the subgroup of participants who received two doses of 177Lu-PSMA-617 followed by adaptive dosing.

IX. To evaluate and compare efficacy between the subgroup of participants who received Schedule 1 versus Schedule 2 dosing.

X. To evaluate and compare efficacy between the subgroup of participants who have received prior taxane chemotherapy versus participants who were taxane-naïve at the time of study entry.

OUTLINE:

Participants will receive two doses of 177Lu-PSMA-617 and may continue treatment for up to a total of six total doses in the absence of unequivocal clinical progression, or unacceptable toxicity, with minimum interval of 6 weeks between doses. Participants will also receive pembrolizumab and may continue study treatment until unequivocal evidence of clinical progression or at physician’s discretion based on clinical evaluation. Participants will undergo safety follow-up visits approximately 30 days and 90 days following the end of treatment visit. Participants will then be seen in clinic or contacted by telephone every 3 months to assess survival/disease/anti-cancer therapy status until death, withdrawal of consent, or the end of the study, whichever occurs first until study closure.