177Lu-PSMA-617 + Pembrolizumab for Prostate Cancer

Overseen By Patricia Li

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: University of California, San Francisco

Must be taking: LHRH analogues

Must not be taking: Immune checkpoint inhibitors

Disqualifiers: Untreated brain metastases, Autoimmune disease, Cardiovascular disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 22

Duration: 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of treatments, 177Lu-PSMA-617 and pembrolizumab, to determine their effectiveness in treating prostate cancer that has spread and resists hormone therapy. 177Lu-PSMA-617 targets cancer cells with radiation, while pembrolizumab (KEYTRUDA) aids the immune system in fighting the cancer. The trial explores different dosing schedules to identify the best approach. It seeks participants with prostate cancer that continues to grow despite hormone therapy and have experienced disease progression. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new combination therapy.

Do I need to stop my current medications for the trial?

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, except for LHRH analogue, within 14 days before starting the study treatment. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Lutetium Lu 177-PSMA-617 is usually well-tolerated. One study found it has a good safety record with fewer serious side effects than other prostate cancer treatments, with most side effects being mild to moderate.

For pembrolizumab, studies indicate it is safe for many prostate cancer patients. Some patients experience side effects, but these are often manageable. This treatment helps the immune system fight cancer cells, which can sometimes lead to inflammation in the body.

Overall, both treatments have demonstrated acceptable safety in past research. However, since this is an early phase trial, the researchers are focusing on learning more about safe doses and schedules for using these drugs together. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of lutetium Lu 177-PSMA-617 and pembrolizumab for prostate cancer because it represents a novel approach compared to existing treatments. Most standard treatments, like hormone therapy and chemotherapy, focus on reducing or blocking hormones that fuel cancer growth or directly killing cancer cells through toxic agents. In contrast, lutetium Lu 177-PSMA-617 is a targeted radioligand therapy that specifically binds to the PSMA protein on prostate cancer cells and delivers radiation directly to them, minimizing damage to surrounding tissues. Pembrolizumab, on the other hand, is an immunotherapy drug that helps the immune system recognize and attack cancer cells. This combination aims to enhance the precision and efficacy of treatment by both directly targeting cancer cells and boosting the body's immune response.

What evidence suggests that this trial's treatments could be effective for prostate cancer?

Research has shown that Lutetium Lu 177-PSMA-617 holds promise for treating advanced prostate cancer that no longer responds to hormone therapy. In studies, about half of the patients experienced a significant drop in PSA levels, a marker used to monitor prostate cancer. Many patients also reported less pain and lived for about 12 months on average after treatment.

For pembrolizumab, research indicates it can be effective for patients with certain genetic traits, such as high microsatellite instability (MSI-H). About 39% of these patients saw their PSA levels decrease by 50% or more. In this trial, participants will receive different dosing schedules of Lutetium Lu 177-PSMA-617 and pembrolizumab. The goal of combining these treatments is to enhance the body's ability to fight cancer and improve patient outcomes. ^{1 4 6 7 8}

Who Is on the Research Team?

Rahul Aggarwal, MD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for patients with metastatic castration-resistant prostate cancer who've progressed after treatment with androgen signaling inhibitors. They must have good blood counts, organ function, agree to contraception, and not have untreated brain metastases or certain other health conditions.

Inclusion Criteria

If you have had a procedure called vasectomy, which prevents pregnancy, you will still be considered capable of having children for this study.

Patients must provide consent to comply to recommended radioprotection precautions during study

Hemoglobin > 9.0 g/dL

Exclusion Criteria

I had radiotherapy over 2 weeks ago, with no ongoing side effects and didn't need steroids.

Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial

Any condition that, in the opinion of the principal investigator, would impair the patient's ability to comply with study procedures

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive lutetium Lu 177-PSMA-617 and pembrolizumab according to one of three dosing schedules. Treatment with pembrolizumab repeats every 21 days for up to 35 cycles (2 years).

2 years

Every 21 days

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

4 weeks

1 visit (in-person)

Extension

Participants who achieve stable disease or better may receive 17 additional cycles (approximately 1 year) of pembrolizumab.

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Lutetium Lu 177-PSMA-617
• Pembrolizumab

Trial Overview The study tests a combination of 177Lu-PSMA-617 (a radioactive drug targeting prostate cancer cells) and pembrolizumab (an immunotherapy). It aims to find the best dose and schedule for treating advanced prostate cancer by enhancing the body's immune response against tumors.

How Is the Trial Designed?

Group I: Part B: Recommended Phase 2 Dosing Schedule (RP2DS) (lutetium Lu 177-PSMA-617, pembrolizumab) Experimental Treatment 2 Interventions

Participants will receive the RP2DS determined in Part A. Treatment with pembrolizumab repeats every 21 days for up to 35 cycles (2 years) in the absence of disease progression or unacceptable toxicity. Participants who achieve SD or better may receive 17 additional cycles (approximately 1 year) of pembrolizumab.

Group II: Part A: Dosing Schedule 3 (lutetium Lu 177-PSMA-617, pembrolizumab) Experimental Treatment 2 Interventions

Starting day -21, participants receive pembrolizumab IV over 30 minutes. Participants also receive lutetium Lu 177-PSMA-617 IV over 20-30 minutes on day 1. Treatment with pembrolizumab repeats every 21 days for up to 35 cycles (2 years) in the absence of disease progression or unacceptable toxicity. Participants who achieve SD or better may receive 17 additional cycles (approximately 1 year) of pembrolizumab.

Group III: Part A: Dosing Schedule 2 (lutetium Lu 177-PSMA-617, pembrolizumab) Experimental Treatment 2 Interventions

Participants receive lutetium Lu 177-PSMA-617 IV over 20-30 minutes and pembrolizumab IV over 30 minutes on day 1. Treatment with pembrolizumab repeats every 21 days for up to 35 cycles (2 years) in the absence of disease progression or unacceptable toxicity. Participants who achieve SD or better may receive 17 additional cycles (approximately 1 year) of pembrolizumab.

Group IV: Part A: Dosing Schedule 1 (lutetium Lu 177-PSMA-617, pembrolizumab) Experimental Treatment 2 Interventions

Participants receive lutetium Lu 177-PSMA-617 IV over 20-30 minutes on day 1. Beginning in cycle 2, participants receive pembrolizumab IV over 30 minutes on day 1. Treatment with pembrolizumab repeats every 21 days for up to 35 cycles (2 years) in the absence of disease progression or unacceptable toxicity. Participants who achieve stable disease (SD) or better may receive 17 additional cycles (approximately 1 year) of pembrolizumab.

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

Prostate Cancer Foundation

Collaborator

Trials

52

Recruited

3,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2107322

Lutetium-177–PSMA-617 for Metastatic Castration ... This radioligand therapy has been associated with encouraging biochemical and radiographic response rates, reduced pain, and low toxicity in multiple early- ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37818966/

The real-world outcomes of Lutetium-177 PSMA-617 ... The Lu-177 PSMA-617 RLT led to a significant PSA response, with 50.6% of patients achieving a >50% decrease in PSA levels. Median overall ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.82

Survival outcomes of patients (pts) with metastatic ... For pts treated with Lu, the median TTNT was 8.5 months (95% CI, 7.3 – 9.8), and the median OS was 12 months (95% CI, 11 – 15). Median TTNT and ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S258893112300161X

Real-world Outcomes and Predictive Biomarkers for 177 ... We found that 177Lu PSMA is an effective treatment option in real-world practice. A PSA (prostate-specific antigen) decrease of ≥30% after the first two therapy ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9803619/

Therapeutic Outcomes of 177Lu-PSMA Targeted Therapy ... The outcomes of 177Lu-PSMA targeted therapy have demonstrated an acceptable response rate in the metastatic castration-resistant prostate cancer (mCRPC) (5).

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10071785/

Safety and Survival Outcomes of 177Lu-Prostate-Specific ... The VISION study investigated a β-emitter, 177Lu-PSMA-617, targeting PSMA-expressing cells and found prolonged overall survival and acceptable safety in heavily ...

7. jnm.snmjournals.org jnm.snmjournals.org/content/66/supplement_1/251339

Comparative Safety and Efficacy of 177Lu-PSMA-617 and ... In this first comparative analysis of 177 Lu-PSMA-617 and 177 Lu-PSMA-I&T RLT in Taiwanese mCRPC patients, both agents demonstrated similar safety and efficacy.

8. annalsofoncology.org annalsofoncology.org/article/S0923-7534(25)00852-X/fulltext

Final overall survival and safety analyses of the phase III ... Lu-PSMA-617 had a favourable safety profile, with a lower incidence of grade 3-5 adverse events (AEs) compared with ARPI change, and no new ...