Lutetium Lu 177 + Sipuleucel-T for Prostate Cancer

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: City of Hope Medical Center

Must be taking: GnRH analogue

Must not be taking: Anticancer therapy, Corticosteroids

Disqualifiers: Liver disease, CNS malignancy, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 6

Duration: 36 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach for treating prostate cancer that has spread and continues to grow despite treatments blocking male hormones (castration-resistant prostate cancer). Researchers compare two treatments: one uses a special radioactive drug (177^Lu-PSMA-617, also known as Lutetium Lu 177 Vipivotide Tetraxetan) that targets and kills cancer cells, and the other combines this drug with a vaccine (sipuleucel-T) designed to boost the immune system to fight the cancer. The goal is to determine if adding the vaccine enhances the treatment's effectiveness or safety. This trial may suit men with prostate cancer that has spread and isn't responding to hormone-blocking treatments. 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 innovative therapy.

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

The trial requires that you stop any approved or investigational anticancer therapy, including chemotherapy, hormonal therapy, or radiotherapy, at least 4 weeks before starting the study treatment. Other specific medications and supplements must also be stopped 28 days before joining the trial.

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

Research has shown that Lutetium Lu 177 (177^Lu)-PSMA-617 is generally safe for patients with advanced, treatment-resistant prostate cancer. Studies found that more than half of the patients experienced a significant drop in PSA levels, a marker used to track prostate cancer. However, some patients had reduced levels of certain blood cells, such as lymphocytes, which help fight infections.

When combined with Sipuleucel-T, a type of cancer vaccine, 177^Lu-PSMA-617 also appears safe. Some evidence suggests this combination might be more effective than 177^Lu-PSMA-617 alone, but further research is needed to confirm this.

In summary, both treatments show promise in terms of safety, with some side effects related to blood cell levels. Ongoing research aims to better understand the effectiveness of these treatments together. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Lutetium Lu 177 combined with Sipuleucel-T for prostate cancer because it introduces a unique approach that differs from standard treatments like hormone therapy and chemotherapy. Lutetium Lu 177 Vipivotide Tetraxetan is a targeted radioligand therapy that binds to the PSMA protein on prostate cancer cells, delivering radiation directly to the tumor and potentially sparing healthy tissue. This targeted mechanism is a significant departure from traditional systemic therapies, which affect both cancerous and healthy cells. Additionally, Sipuleucel-T is an immunotherapy that stimulates the patient’s immune system to attack prostate cancer cells, adding another layer of defense. Together, these treatments offer a dual-action strategy that combines direct tumor targeting with immune system enhancement, potentially improving efficacy and minimizing side effects compared to conventional options.

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

Research shows that lutetium Lu 177 PSMA-617 effectively treats advanced prostate cancer that no longer responds to hormone therapy. Studies indicate that patients using this treatment have a median survival time of 15.3 months. Additionally, many patients experienced improvements in their PSA levels, a protein that can indicate prostate cancer, with 55.6% seeing a reduction of 50% or more. In this trial, some participants will receive lutetium Lu 177 PSMA-617 alone, while others will receive it with Sipuleucel-T. Early results suggest that this combination could be even more effective, as it aims to strengthen the immune system's ability to fight cancer, potentially leading to better outcomes for patients. ^{2 3 6 7 8}

Who Is on the Research Team?

Alex Chehrazi-Raffle

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for men with prostate cancer that has spread and resists treatment after attempts to block testosterone. Participants must have a specific protein on their tumor cells, be able to undergo certain scans, and provide biospecimens.

Inclusion Criteria

Serum creatinine within normal limits

Coagulation parameters within normal limits

Documented informed consent of the participant and/or legally authorized representative

Exclusion Criteria

Treatment with investigational products

Inability to comply with study procedures

Potential compliance issues

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive 177^Lu-PSMA-617 IV every 6 weeks for up to 6 cycles. In Arm B, starting during week 8, patients also receive sipuleucel-T IV every 2 weeks for up to 3 doses.

36 weeks

6 visits (in-person) for 177^Lu-PSMA-617, additional 3 visits (in-person) for sipuleucel-T in Arm B

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up at 30 days, every 3 months for up to 1 year, then every 6 months until progression.

Up to 3 years

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Lutetium Lu 177 Vipivotide Tetraxetan
• Sipuleucel-T

Trial Overview The study compares the effects of a radioactive drug (177^Lu-PSMA-617) alone versus combined with an immune system booster (Sipuleucel-T). It aims to see if the combination is safer or more effective in killing prostate tumor cells.

How Is the Trial Designed?

Group I: Arm B (177^Lu-PSMA-617, sipuleucel-T) Experimental Treatment 8 Interventions

Patients receive 177\^Lu-PSMA-617 IV. Treatment repeats every 6 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Starting during week 8 of treatment, patients receive sipuleucel-T IV over 1 hour. Treatment repeat every 2 weeks for up to 3 doses in the absence of disease progression or unacceptable toxicity. Patients also undergo leukapheresis, blood sample collection, PSMA PET/CT, bone scan, and MRI throughout the study. Additionally, patients may undergo MRI or CT of the brain throughout the study.

Group II: Arm A (177^Lu-PSMA-617) Active Control 7 Interventions

Patients receive 177\^Lu-PSMA-617 IV. Treatment repeats every 6 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection, PSMA PET/CT, bone scan, and MRI throughout the study. Additionally, patients may undergo MRI or CT of the brain throughout the study.

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.63

Patient characteristics and overall survival with lutetium (Lu ... The median OS from start of 177Lu-PSMA-617 therapy was 15.3 months (95% confidence interval [CI]: 14.6–16.3); a total of 137/643 (21.3%) ...

2. urotoday.com urotoday.com/conference-highlights/asco-gu-2025/asco-gu-2025-prostate-cancer/158159-asco-gu-2025-patient-characteristics-and-overall-survival-with-lutetium-lu177-vipivotide-tetraxetan-177lu-psma-617-a-real-world-analysis-of-early-adopters.html

Patient characteristics and overall survival with lutetium ... The median overall survival from the start of ¹⁷⁷Lu-PSMA-617 therapy was 15.3 months (95% CI: 14.6–16.3), with 137 of 643 patients (21.3%) ...

3. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2823605

Lu-177 PSMA in Survival of Metastatic Castration-Resistant ... This comparative effectiveness research investigates factors associated with the difference in the observed effect of lutetium Lu 177 ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2452109425002040

Lutetium Lu 177 Vipivotide Tetraxetan Efficacy and Toxicity ... 68.9% of the cohort observed PSA biomarker improvement of ≥10%, and 55.6% with ≥50% PSA reduction. Three patients (6.7%) achieved a complete ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10159870/

FDA Approval Summary: Lutetium Lu 177 Vipivotide ... Efficacy results. The co-primary endpoint of OS was statistically significant, with patients randomized to receive 177Lu-PSMA-617 plus BSoC having prolonged ...

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

Survival outcomes of patients (pts) with metastatic ... Survival outcomes of patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) receiving lutetium-177-PSMA-617 (Lu) based on ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05803941

NCT05803941 | Long-Term Safety of Lutetium (177Lu) ... The purpose of this post-marketing study is to further characterize the long-term outcome of known or potential risks of lutetium (177Lu) vipivotide ...

8. jnm.snmjournals.org jnm.snmjournals.org/content/66/supplement_1/251288

Patient Characteristics and Prostate-Specific Antigen (PSA ... In this study, over 50% of patients achieved PSA50 response while receiving 177 Lu-PSMA-617, consistent with findings from previous real-world studies.