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

NCT05766371 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 23551NCI-2023-01660
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Castrate Resistant Prostate Cancer; Metastatic Castration-resistant Prostate Cancer; Prostate Cancer; Prostate Carcinoma

Outcome Measures

Primary Outcomes (1)

• 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.

  12 months

Secondary Outcomes (25)

• Overall median radiographic rPFS

  Up to 5 years

• Objective response rate (ORR)

  Up to 10 months

• Median duration of objective response (DOR)

  Up to 10 months

• Proportion of participants with 50% decline in PSA (PSA50)

  Up to 10 months

• Proportion of participants with 90% decline in PSA (PSA90)

  Up to 10 months

Study Arms (1)

Pembrolizumab, 177Lu-PSMA-617

EXPERIMENTAL

Participants will receive 400 mg of Pembrolizumab every 6 weeks and an infusion of 7.4 gigabequerel (GBq) (+/- 10%) of 177Lu-PSMA-617 on Cycle 1 Day 1 (of a 28 day cycle), and 6 weeks later, then at the first subsequent rise in PSA for up to six total doses, in the absence of unequivocal clinical progression, radiographic progression, or unacceptable toxicity, with a minimum interval of 6 weeks between doses.

Drug: Pembrolizumab; Drug: 177Lu-PSMA-617

Interventions

Pembrolizumab DRUG

Given IV

Also known as: Keytruda

Pembrolizumab, 177Lu-PSMA-617

177Lu-PSMA-617 DRUG

Given IV

Also known as: Lutetium-177-PSMA-617, (177Lu)-PSMA-617

Pembrolizumab, 177Lu-PSMA-617

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Male participants who are at least 18 years of age on the day of signing informed consent.
• 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.
• Prior progression on at least one second generation androgen signaling inhibitor including abiraterone, apalutamide, darolutamide, and/or enzalutamide.
• Adverse events related to prior anti-cancer treatment (excluding LHRH analogs) must have recovered to Grade \<= 1 (except for any grade alopecia and grade \<= 2 neuropathy).
• Prior radiotherapy is allowed if the last radiotherapy treatment was greater than 2 weeks from start of study treatment on cycle 1, day 1 (C1D1). Note- Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (\<=2 weeks of radiotherapy) to non-central nervous system (CNS) disease.
• 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.
• Eastern Cooperative Oncology Group (ECOG) performance status \<= 1 (Karnofsky \>= 70%).
• Demonstrates adequate organ function as defined below:
• Adequate bone marrow function:
• absolute neutrophil count \>=1,500/microliter (mcL)
• platelets \>=100,000/mcL
• hemoglobin \> 9.0 g/dL
• Adequate hepatic function:
• total bilirubin \<= 1.5 x upper limit of normal (ULN). In patients with known or suspected Gilbert's disease, direct bilirubin \<= ULN

You may not qualify if:

• 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.
• Receipt of prior PSMA-directed treatment (e.g., radiotherapy, immunotherapy, or antibody-drug conjugate).
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-Programmed cell death-ligand 2 (PD-L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), OX 40, CD137).
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment on C1D1. Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
• Receipt of \> 2 lines of prior taxane-based chemotherapy.
• Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
• Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Note: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) or treatment with drugs (e.g., neomercazole, carbimazole, etc.) that function to decrease the generation of thyroid hormone by a hyper-functioning thyroid gland (e.g., in Graves' disease) is not considered a form of systemic treatment of an autoimmune disease.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy at a prednisone equivalent dose of \> 10 mg daily or other form of immunosuppressive therapy within 7 days prior to first dose of study drug.
• Has a history of (non-infectious) ≥ grade 2 pneumonitis/interstitial lung disease that required steroids within past 2 years or has current ≥ grade 1 pneumonitis/ interstitial lung disease at the time of study enrollment.
• Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug on C1D1. Note-Administration of a killed vaccine is allowed.
• Patients who because of age, general medical or psychiatric condition, or physiologic status cannot give valid informed consent.
• Has clinically significant cardiovascular disease including, but not limited to:

Sponsors & Collaborators

• University of California, San Francisco: lead
• Merck Sharp & Dohme LLC: collaborator
• Prostate Cancer Foundation: collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

RECRUITING

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

pembrolizumab; Pluvicto

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Officials

• Rahul Aggarwal, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

UCSF Genitourinary Medical Oncology Recruitment

CONTACT

877-827-3222; GUTrials@ucsf.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2023
• First Posted: March 13, 2023
• Study Start: December 15, 2023
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): May 31, 2031
• Last Updated: April 17, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)