Flexible Dosing of 177Lu-PSMA-617 for Advanced Prostate Cancer

Overseen By Stephanie Lira

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Jonsson Comprehensive Cancer Center

Disqualifiers: Prior 177Lu-PSMA-617, Low GFR, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: Up to 72 weeks

90 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the optimal use of 177Lu-PSMA-617, a type of radioligand therapy, for advanced prostate cancer that has spread and resisted other treatments. The main goal is to determine if some patients can benefit from a more flexible treatment schedule, possibly taking breaks ("treatment holidays") based on their response to the therapy. The trial compares two groups: one receives the treatment every 6 weeks for up to 12 cycles with possible breaks, and the other follows a fixed schedule of 6 cycles without breaks. Men with prostate cancer who have visible cancer spread on scans and have tried both chemotherapy and hormone-blocking treatments might be suitable for this study. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, there must be at least 6 weeks between your last myelosuppressive therapy and the first cycle of the trial treatment.

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

Research has shown that 177Lu-PSMA-617, a treatment for advanced prostate cancer, is generally safe for patients. Studies have found that most people tolerate this treatment well, with side effects typically mild to moderate and similar to those of other cancer treatments. For example, one study found that while some patients experienced mild to moderate side effects, these were often temporary. Another study demonstrated that this treatment helped patients live longer without the cancer worsening, indicating its effectiveness without causing serious harm. Overall, these findings suggest that 177Lu-PSMA-617 is relatively safe for use. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about 177Lu-PSMA-617 for advanced prostate cancer because it offers a novel approach by specifically targeting prostate-specific membrane antigen (PSMA) on cancer cells. Unlike traditional treatments such as chemotherapy or androgen deprivation therapy, which affect both cancerous and healthy cells, 177Lu-PSMA-617 delivers targeted radiation directly to the cancer cells, potentially reducing side effects. Moreover, its flexible dosing schedule allows for treatment adjustments based on patient response, which may improve outcomes and quality of life. This precision-targeted therapy represents a promising advancement in the fight against prostate cancer.

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

Research has shown that 177Lu-PSMA-617 effectively treats advanced prostate cancer. Studies found that 68.9% of patients experienced a significant drop in their PSA (prostate-specific antigen) levels, indicating the treatment's effectiveness. Additionally, 55.6% of patients saw their PSA levels reduced by at least half. This treatment is associated with a median overall survival of 15.3 months, offering hope for patients with advanced disease. In this trial, participants will receive 177Lu-PSMA-617 in one of two dosing regimens—either with flexible dosing intervals or a fixed schedule—to evaluate its effectiveness and safety. Experts agree that 177Lu-PSMA-617 can improve outcomes for those who have not responded to previous treatments. ^{2 3 4 6 7}

Who Is on the Research Team?

Jeremie Calais

Principal Investigator

UCLA / Jonsson Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for individuals with metastatic castration-resistant prostate cancer, which continues to grow despite low testosterone levels from traditional hormone therapy. Participants should have PSMA receptors on tumor cells and be suitable for a flexible treatment schedule.

Inclusion Criteria

White blood cell (WBC) ≥ 1500/ul

Absolute neutrophil count (ANC) ≥ 1000 mm^3

Patients must have the ability to understand and sign an approved informed consent form (ICF)

Exclusion Criteria

It has been less than 6 weeks since my last strong cancer treatment.

My kidney function is low, with a GFR under 30 ml/min.

I have previously received 177Lu-PSMA-617 therapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 177Lu-PSMA-617 intravenously every 6 weeks for up to 12 cycles, with potential treatment holiday periods based on response assessments

Up to 72 weeks

1 visit every 6 weeks

Treatment Holiday

Participants may have treatment holiday periods based on response assessments, monitored with PSMA PET/CT every 12 weeks

Variable, based on response

1 visit every 12 weeks during holiday

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

24 months

1 visit every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Lutetium Lu 177 Vipivotide Tetraxetan

Trial Overview The study is testing a new dosing schedule of the drug 177Lu-PSMA-617 over 12 cycles versus the standard 6 cycles. It includes imaging techniques like PET scans and CTs to monitor progress, along with 'treatment holiday' periods.

How Is the Trial Designed?

Group I: Arm I (177Lu-PSMA-617) Experimental Treatment 7 Interventions

Patients receive 177Lu-PSMA-617 IV once every 6 weeks on study. Beginning with the third cycle, treatments may be postponed beyond the 6 weeks interval based on defined response criteria ("treatment holiday" period). Treatment repeats every 6 weeks for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients receive 68Ga-PSMA-11 IV and undergo PSMA PET/CT throughout the trial. Patients also undergo SPECT/CT, PET/CT, or CT on the trial.

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

Patients receive 177Lu-PSMA-617 IV once every 6 weeks on study. Treatment repeats every 6 weeks for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients receive 68Ga-PSMA-11 IV and undergo PSMA PET/CT throughout the trial. Patients also undergo SPECT/CT, PET/CT, or CT on the trial.

Lutetium Lu 177 Vipivotide Tetraxetan is already approved in United States, European Union for the following indications:

Approved in United States as Pluvicto for:

• Metastatic castration-resistant prostate cancer (mCRPC) in adults who have been treated with androgen receptor inhibitors and taxane-based chemotherapy

Approved in European Union as Pluvicto for:

• Treatment of adult patients with progressive PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor pathway inhibitors and taxane-based chemotherapy

Who Is Running the Clinical Trial?

Jonsson Comprehensive Cancer Center

Lead Sponsor

Trials

373

Recruited

35,200+

Novartis Pharmaceuticals

Industry Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Published Research Related to This Trial

Pluvicto (lutetium Lu 177 vipivotide tetraxetan) is an approved treatment for adult patients with advanced prostate cancer that expresses the prostate-specific membrane antigen (PSMA).

This therapy is specifically indicated for patients who have already undergone treatment with androgen receptor pathway inhibitors and taxane-based chemotherapy, highlighting its role in later-stage cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Drug for Metastatic Castration-Resistant Prostate Cancer. Aschenbrenner, DS.[2022]

177Lu-vipivotide tetraxetan is a targeted radiopharmaceutical that effectively treats metastatic castration-resistant prostate cancer (mCRPC) by delivering beta-radiation directly to cancer cells, demonstrating safety and tolerability in clinical trials.

Approved by the FDA in March 2022 based on the VISION trial, this therapy is particularly beneficial for patients who have already undergone androgen receptor pathway inhibition and taxane-based chemotherapy, highlighting its role as a new treatment option in advanced prostate cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lutetium Lu 177 vipivotide tetraxetan for metastatic castration-resistant prostate cancer. Shah, H., Ravi, P., Sonpavde, G., et al.[2023]

The FDA approved Pluvicto (177Lu-PSMA-617) for treating metastatic castration-resistant prostate cancer (mCRPC) in patients who have undergone prior treatments, showing a significant improvement in overall survival (15.3 months vs. 11.3 months with standard care) in a trial with 831 participants.

Common side effects of Pluvicto include fatigue, dry mouth, and nausea, with notable laboratory abnormalities such as decreased lymphocytes and hemoglobin occurring in over 30% of patients, indicating the need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Lutetium Lu 177 Vipivotide Tetraxetan for Patients with Metastatic Castration-Resistant Prostate Cancer. Fallah, J., Agrawal, S., Gittleman, H., et al.[2023]

Lutetium Lu 177 vipivotide tetraxetan (PLUVICTO™) is a targeted radioligand therapy approved in the USA for treating metastatic castration-resistant prostate cancer (mCRPC) that expresses prostate-specific membrane antigen (PSMA), based on positive results from the phase 3 VISION trial.

This therapy specifically targets PSMA, which is overexpressed in prostate cancer cells, allowing for a more effective treatment option for patients who have already undergone other therapies like androgen receptor inhibition and taxane-based chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lutetium Lu 177 Vipivotide Tetraxetan: First Approval. Keam, SJ.[2022]

In a phase 3 trial involving 831 patients with metastatic castration-resistant prostate cancer, the addition of [177Lu]Lu-PSMA-617 to standard care significantly delayed the time to first symptomatic skeletal event, with a median of 11.5 months compared to 6.8 months for standard care alone.

Patients receiving [177Lu]Lu-PSMA-617 also reported improved health-related quality of life and less pain, although there were some serious adverse events, including hematological issues, indicating the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-related quality of life and pain outcomes with [177Lu]Lu-PSMA-617 plus standard of care versus standard of care in patients with metastatic castration-resistant prostate cancer (VISION): a multicentre, open-label, randomised, phase 3 trial. Fizazi, K., Herrmann, K., Krause, BJ., et al.[2023]

[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]

Citations

1. 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 ...

2. 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%) ...

3. jnm.snmjournals.org jnm.snmjournals.org/content/early/2025/09/25/jnumed.125.270704

First-Line [177Lu]Lu-PSMA-617 Therapy Without ADT ... In the phase 3 PSMAfore trial, [177Lu]Lu-PSMA-617 demonstrated significantly improved radiographic progression-free survival compared with an ...

4. novartis.com novartis.com/news/media-releases/psmaddition-data-show-novartis-pluvictotm-delays-progression-end-stage-prostate-cancer

PSMAddition data show Novartis Pluvicto™ delays ... PluvictoTM plus standard of care (ARPI + ADT) significantly reduced risk of progression or death by 28% (HR 0.72) versus SoC alone, ...

5. 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%) ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12481865/

Adverse events associated with Lutetium-177-PSMA-617 ... Pluvicto® can bind to prostate cancer cells expressing prostate-specific membrane antigen and induce DNA damage through the radiation released ...

7. 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 ...