Lutetium (177Lu) Vipivotide Tetraxetan + ARPI for Prostate Cancer

(PSMAndARPI Trial)

Recruiting at 13 trial locations

Overseen By Novartis Pharmaceuticals

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Novartis Pharmaceuticals

Must be taking: ARPI

Must not be taking: Taxane chemotherapy

Disqualifiers: CNS metastases, Cardiac disease, Nephropathy, 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

Compensation: Varies

Number of Visits: 7

Duration: 36 weeks

420 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if combining a new treatment, AAA617 (Lutetium (177Lu) Vipivotide Tetraxetan), with existing medications like abiraterone or enzalutamide can benefit men with a specific type of prostate cancer that has recurred after previous treatments. Researchers are assessing whether this combination extends the time patients live without cancer progression compared to using AAA617 alone. Men with prostate cancer that has spread, indicated by symptoms such as rising PSA levels or new bone lesions, and who have not responded to certain treatments, might be eligible to join. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that you should not have had certain treatments like Strontium-89 or Radium-223 within 6 weeks before starting the trial. It's best to discuss your current medications with the trial team to be sure.

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

Research has shown that Lutetium (177Lu) Vipivotide Tetraxetan has produced positive results in past patients. In studies, more than half of the patients experienced a significant decrease in their PSA levels, a marker used to track prostate cancer. However, researchers continue to investigate its long-term safety.

Studies have provided extensive safety information for the combination of Abiraterone and Enzalutamide. These medications are generally well-tolerated, though some reports indicate heart-related problems, particularly with Abiraterone. Enzalutamide tends to yield better outcomes compared to Abiraterone alone.

Overall, both the combination treatment and the Lutetium treatment have been used in various situations, with a history of safety, though potential risks exist. Participating in a study like this one may involve some risks, but it also offers an opportunity to try new treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Lutetium (177Lu) Vipivotide Tetraxetan, also known as AAA617, for treating prostate cancer because it uses a novel approach called radioligand therapy. Unlike traditional hormone therapies, which target androgen receptors to slow cancer growth, AAA617 delivers targeted radiation directly to cancer cells, potentially offering a more precise attack on tumors. Additionally, when combined with standard androgen receptor pathway inhibitors like Abiraterone and Enzalutamide in one of the trial arms, AAA617 could enhance the overall effectiveness, offering hope for improved patient outcomes.

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

In this trial, participants will receive either Lutetium (177Lu) Vipivotide Tetraxetan alone or with Abiraterone and Enzalutamide. Research has shown that Lutetium (177Lu) Vipivotide Tetraxetan can significantly lower prostate-specific antigen (PSA) levels, with more than half of patients experiencing a drop of over 50%. This suggests that the treatment may effectively slow disease progression. Additionally, studies have revealed that patients typically live about 15 months after starting this treatment. For Abiraterone and Enzalutamide, research indicates that both drugs help manage prostate cancer similarly, with comparable control over tumor growth and survival rates. This combination, therefore, has the potential to improve outcomes for those whose cancer has progressed despite previous treatments. ^{1 2 3 6 7}

Who Is on the Research Team?

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for men with advanced prostate cancer that has spread and is PSMA-positive. They must have previously progressed on ARPI therapy, not received taxane in the CRPC setting, have low testosterone levels, show disease progression either in soft tissue or bone, and be able to perform daily activities (ECOG 0-2).

Inclusion Criteria

My cancer shows up on a special PET scan that looks for a protein.

My testosterone levels are very low (<50 ng/dL or <1.7 nmol/L).

I have mCRPC and it got worse after treatment with ARPI.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive AAA617 with or without ARPI every 6 weeks for 6 cycles

36 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Regular visits as per study protocol

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Abiraterone
• Enzalutamide
• Lutetium (177Lu) Vipivotide Tetraxetan

Trial Overview The study compares a combination of AAA617 plus ARPI against AAA617 alone to see if it can extend the time patients live without their cancer getting worse. Participants will receive AAA617 every cycle for six cycles at a specific dose.

How Is the Trial Designed?

Group I: Arm A: AAA617 and ARPI Experimental Treatment 3 Interventions

AAA617 and ARPI (Enzalutamide, Abiraterone): * AAA617 will be administered once every 6 weeks (1 cycle) for a planned 6 cycles. * ARPI will be administered from 14 days (+ 7 days) before first dose of AAA617 until participant is no longer clinically benefiting, or experiences unacceptable toxicity or if investigator determines that the patient should discontinue ARPI.

Group II: Arm B: AAA617 alone Active Control 1 Intervention

AAA617 alone: Control Arm B participants will receive a dose of AAA617 which will be administered once every 6 weeks (1 cycle) for a planned 6 cycles.

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals

Lead 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

Citations

1. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2840898

Abiraterone vs Enzalutamide for Metastatic Hormone ... This cohort study evaluates clinical outcomes in patients with metastatic hormone-sensitive prostate cancer treated with abiraterone acetate ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12504157/

Comparative effectiveness and safety of enzalutamide ... Effectiveness outcomes included all-cause death, prostate cancer-related death, and treatment failure. Safety outcomes included major adverse CV ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.5053

Real-world comparative effectiveness and cardiovascular ... The objective of this study was to compare real-world overall survival and risk of major adverse cardiovascular events (MACE) between initiators of abiraterone ...

4. nature.com nature.com/articles/s41391-024-00816-0

Real-world overall survival with abiraterone acetate versus ... 1L abiraterone was associated with worse OS versus enzalutamide in the overall population and among subgroups with older age and comorbidities.

5. hmpgloballearningnetwork.com hmpgloballearningnetwork.com/site/vht/news/abiraterone-and-enzalutamide-show-comparable-outcomes-us-veterans-metastatic-prostate

Abiraterone and Enzalutamide Show Comparable ... Among US veterans with metastatic hormone-sensitive prostate cancer, abiraterone and enzalutamide achieved similar tumor growth rates and ...

6. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2822420

Abiraterone or Enzalutamide for Patients With Metastatic ... The study showed that initial enzalutamide treatment, in general, was associated with more favorable outcomes than initial abiraterone acetate ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S1879406824004211

Real-world effectiveness and cardiovascular safety of ... The objective of this study was to compare the real-world effectiveness and cardiovascular safety of these agents, drawing from a cohort of older adult ...