Pembrolizumab + 177Lu-PSMA-617 for Prostate Cancer

Recruiting in Palo Alto (17 mi)

Overseen by Rahul Aggarwal, MD

Age: 18+

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: University of California, San Francisco

Must be taking: LHRH analogues

Must not be taking: Anti-PD-1, Anti-PD-L1

Disqualifiers: Autoimmune disease, Cardiovascular disease, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

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).

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must not have received other systemic anti-cancer therapies within 14 days before starting the study treatment. LHRH analogues are an exception and must be continued if you haven't had a bilateral orchiectomy (surgical removal of both testicles).

What data supports the effectiveness of the treatment Pembrolizumab + 177Lu-PSMA-617 for Prostate Cancer?

Research shows that 177Lu-PSMA-617, a treatment that targets prostate cancer cells, has been effective in treating advanced prostate cancer, especially when combined with other therapies like pembrolizumab, which helps the immune system fight cancer. However, some patients may not respond, and ongoing studies are exploring ways to improve its effectiveness. ^{1 2 3 4 5}

Is the combination of Pembrolizumab and 177Lu-PSMA-617 safe for humans?

The combination of Pembrolizumab and 177Lu-PSMA-617 has been studied for safety in patients with prostate cancer. 177Lu-PSMA-617, also known as Pluvicto, has been approved by the FDA for prostate cancer treatment, indicating it has been evaluated for safety. Clinical trials have investigated its safety and effects, showing it can be used safely in humans, although individual responses may vary. ^{1 4 5 6 7}

How is the drug Pembrolizumab + 177Lu-PSMA-617 unique for prostate cancer treatment?

This drug combines Pembrolizumab, an immune checkpoint inhibitor, with 177Lu-PSMA-617, a radioligand therapy that targets prostate-specific membrane antigen (PSMA) on cancer cells, delivering radiation directly to the tumor. This combination aims to enhance the immune response and improve treatment efficacy for metastatic castration-resistant prostate cancer, which is challenging to treat with existing therapies. ^{1 2 5 8 9}

Research Team

Rahul Aggarwal, MD

Principal Investigator

University of California, San Francisco

Eligibility Criteria

Men over 18 with advanced prostate cancer that's resistant to hormone therapy and has spread, who've had prior treatment fail. They must understand the trial and agree in writing, have a low testosterone level, recovered from past treatments' side effects, no recent vaccines or major surgeries, no severe allergies to pembrolizumab or its ingredients, not on high-dose steroids or immunosuppressants, and be willing to follow safety guidelines.

Inclusion Criteria

Ability to understand and the willingness to sign a written informed consent document

My organs are functioning well.

My testosterone levels are very low (< 50 ng/dL) as required.

Exclusion Criteria

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

I have been treated with specific immune therapy for cancer.

I have brain metastases that have not been treated.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive two doses of 177Lu-PSMA-617 and pembrolizumab, with the possibility of up to six total doses in the absence of clinical progression or unacceptable toxicity.

Up to 36 weeks

Every 6 weeks for up to 6 doses

Safety Follow-up

Participants undergo safety follow-up visits approximately 30 days and 90 days following the end of treatment visit.

3 months

2 visits (in-person)

Long-term Follow-up

Participants are contacted every 3 months to assess survival, disease status, and anti-cancer therapy status until death, withdrawal of consent, or study closure.

Up to 5 years

Every 3 months (in-person or telephone)

Treatment Details

Interventions

• 177Lu-PSMA-617 (Radiopharmaceutical)
• Pembrolizumab (Checkpoint Inhibitor)

Trial Overview The study is testing a combination of Pembrolizumab (an immune system booster) with a radioactive drug called 177Lu-PSMA-617 targeting prostate cancer cells. It's for patients whose cancer worsened after treatments like abiraterone. The goal is to see if this combo helps when standard therapies don't work anymore.

Participant Groups

Group I: Pembrolizumab, 177Lu-PSMA-617 Experimental Treatment 2 Interventions

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.

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

Suresh Gunasekaran

University of California, San Francisco

Chief Executive Officer since 2022

MBA from Southern Methodist University

Dr. Lukejohn Day

University of California, San Francisco

Chief Medical Officer

MD from Stanford University School of Medicine

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Prostate Cancer Foundation

Collaborator

Trials

52

Recruited

3,000+

Findings from Research

In a study involving 43 men with metastatic castration-resistant prostate cancer, a single dose of lutetium-177-PSMA-617 followed by pembrolizumab maintenance was found to be safe, with only 5% of patients experiencing serious treatment-related adverse events.

The treatment showed promising efficacy, with 56% of patients in the second part of the study achieving a confirmed objective response, indicating potential for durable clinical benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-dose 177Lu-PSMA-617 followed by maintenance pembrolizumab in patients with metastatic castration-resistant prostate cancer: an open-label, dose-expansion, phase 1 trial. Aggarwal, R., Starzinski, S., de Kouchkovsky, I., et al.[2023]

In a phase 3 trial involving 831 patients with metastatic castration-resistant prostate cancer, the addition of 177Lu-PSMA-617 to standard care significantly improved both imaging-based progression-free survival (8.7 months vs. 3.4 months) and overall survival (15.3 months vs. 11.3 months).

While 177Lu-PSMA-617 was associated with a higher incidence of grade 3 or above adverse events (52.7% vs. 38.0%), it did not negatively impact the patients' quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. Sartor, O., de Bono, J., Chi, KN., et al.[2023]

In a study of 168 patients undergoing 177Lu-PSMA therapy for metastatic castration-resistant prostate cancer, a higher PD-L2 signature was linked to significantly longer overall survival (OS), suggesting it may enhance treatment response.

Conversely, PD-L1 levels did not show a significant association with patient outcomes, indicating that PD-L2 may be a more relevant biomarker for predicting the efficacy of 177Lu-PSMA therapy, particularly in patients with lower LDH levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysing the tumor transcriptome of prostate cancer to predict efficacy of Lu-PSMA therapy. Handke, A., Kesch, C., Fendler, WP., et al.[2023]

[177Lu]Lu-PSMA-617 is effective in targeting prostate cancer, but some patients do not respond well; ongoing research is exploring combination therapies to improve outcomes for both treatment-naïve and resistant patients.

Combining [177Lu]Lu-PSMA-617 with other treatments, such as alpha radiation emitters and immune checkpoint inhibitors, shows promise in enhancing therapeutic responses, particularly for patients who have developed resistance to initial therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Towards Improving the Efficacy of PSMA-Targeting Radionuclide Therapy for Late-Stage Prostate Cancer-Combination Strategies. Arbuznikova, D., Eder, M., Grosu, AL., et al.[2023]

In a phase 2 trial involving 30 men with metastatic castration-resistant prostate cancer, 57% achieved a significant PSA decline of 50% or more after treatment with Lutetium-177 [177Lu]-PSMA-617, indicating its efficacy in this patient population.

The treatment was associated with low toxicity, with the most common side effects being mild dry mouth and transient nausea, and it also led to clinically meaningful improvements in pain and quality of life for many patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[177Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): a single-centre, single-arm, phase 2 study. Hofman, MS., Violet, J., Hicks, RJ., et al.[2021]

[177Lu]Lu-PSMA-617 (PluvictoTM) is an FDA-approved treatment for prostate cancer specifically for patients with PSMA-positive metastatic castration-resistant prostate cancer who have already undergone other therapies.

This treatment uses a targeted radioligand therapy that delivers radiation directly to tumor cells, effectively killing them while minimizing damage to healthy tissue, as shown in multiple clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[177Lu]Lu-PSMA-617 (PluvictoTM): The First FDA-Approved Radiotherapeutical for Treatment of Prostate Cancer. Hennrich, U., Eder, M.[2022]

177Lu-PSMA-617 therapy has shown promising efficacy in treating metastatic prostate cancer, with a majority of patients experiencing a decline in prostate-specific antigen (PSA) levels, which is associated with longer survival rates.

The analysis of 17 studies indicated that while significant toxicities were infrequent, cytopenias were noted, and factors like performance status and tumor grade were important predictors of treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of 177Lu-PSMA-617 in Patients With Metastatic Castration-Resistant Prostate Cancer. Sun, M., Niaz, MO., Nelson, A., et al.[2020]

The newly developed radionuclide therapy agent [177Lu]Lu-P17-079 ([177Lu]Lu-1) shows high uptake in PSMA-positive tumors and significantly increased bone uptake compared to other agents, indicating its potential effectiveness in targeting both prostate cancer and bone metastases.

PET imaging with [68Ga]Ga-P17-079 confirms the dual-targeting capability of [177Lu]Lu-1, making it a promising candidate for further development in treating prostate cancer with bone metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lu-177-Labeled Hetero-Bivalent Agents Targeting PSMA and Bone Metastases for Radionuclide Therapy. Zha, Z., Ploessl, K., Choi, SR., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Single-dose 177Lu-PSMA-617 followed by maintenance pembrolizumab in patients with metastatic castration-resistant prostate cancer: an open-label, dose-expansion, phase 1 trial. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Prostate Cancer Theranostics: PSMA Targeted Therapy. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Analysing the tumor transcriptome of prostate cancer to predict efficacy of Lu-PSMA therapy. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Towards Improving the Efficacy of PSMA-Targeting Radionuclide Therapy for Late-Stage Prostate Cancer-Combination Strategies. [2023]

6. England pubmed.ncbi.nlm.nih.gov

[177Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): a single-centre, single-arm, phase 2 study. [2021]

7. Switzerland pubmed.ncbi.nlm.nih.gov

[177Lu]Lu-PSMA-617 (PluvictoTM): The First FDA-Approved Radiotherapeutical for Treatment of Prostate Cancer. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Review of 177Lu-PSMA-617 in Patients With Metastatic Castration-Resistant Prostate Cancer. [2020]

9. United States pubmed.ncbi.nlm.nih.gov

Lu-177-Labeled Hetero-Bivalent Agents Targeting PSMA and Bone Metastases for Radionuclide Therapy. [2023]