AAA617 Alone or Combined With ARPI for Prostate Cancer

(PSMACare Trial)

Recruiting at 56 trial locations

Overseen By Novartis Pharmaceuticals

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Novartis Pharmaceuticals

Must be taking: GnRH agonists/antagonists

Must not be taking: Second-gen anti-androgens, CYP17 inhibitors

Disqualifiers: Metastatic disease, Cardiac disease, Seizure, 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: 6

Duration: 36 weeks

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, AAA617 (also known as Lutetium Lu 177 vipivotide tetraxetan), for prostate cancer that no longer responds to hormone therapy but hasn't spread according to standard scans. Researchers aim to determine the effectiveness and safety of this treatment when used alone or with other medications targeting hormone pathways related to prostate cancer. Men with prostate cancer that is PSMA-positive and who continue hormone therapy might be suitable for this study. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in prostate cancer treatment.

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

The trial requires that you continue ongoing androgen deprivation therapy. You must stop using certain medications like estrogens, 5-α reductase inhibitors, and first-generation anti-androgens at least 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 AAA617, also known as Lutetium [177Lu] vipivotide tetraxetan, has demonstrated encouraging results regarding human safety. In one study, when combined with standard treatments like Androgen Receptor Pathway Inhibitors (ARPI) and Androgen Deprivation Therapy (ADT), it reduced the risk of cancer worsening or death by 28%. This suggests that the treatment works well with existing therapies and has a good safety profile.

Moreover, the FDA has approved AAA617 for treating a specific type of advanced prostate cancer, indicating its safety for use. This approval is based on evidence showing it helps patients live longer. Other studies support these findings, showing consistent benefits and manageable side effects when used with ARPI and ADT.

In summary, research suggests that AAA617, whether used alone or with ARPI, is generally well-tolerated and has a proven track record in treating certain prostate cancers. This provides reassurance about its safety for those considering joining the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about AAA617 for prostate cancer because it uses a novel active ingredient, Lutetium [177Lu] vipivotide tetraxetan, which is a radiopharmaceutical. Unlike traditional treatments like hormone therapies or chemotherapy, AAA617 delivers targeted radiation directly to cancer cells, minimizing damage to healthy tissue. This targeted approach not only aims to improve efficacy but also reduces potential side effects, offering a promising new option for patients.

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

Research has shown that AAA617, also known as Lutetium \[177Lu\] vipivotide tetraxetan, may effectively treat prostate cancer. Studies indicate that it can reduce prostate-specific antigen (PSA) levels by more than 50% in over half of the patients. On average, patients using this treatment live about 15 months. In this trial, participants in Arm A will receive AAA617 alone, while those in Arm B will receive AAA617 combined with Androgen Receptor Pathway Inhibitors (ARPI). When combined with ARPI, the chance of cancer worsening or causing death drops by 28% compared to standard treatments alone. These findings suggest that AAA617, both alone and with ARPI, could be a useful option for managing prostate cancer. ^{1 3 6 7 8}

Who Is on the Research Team?

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for adults over 18 with advanced prostate cancer that hasn't spread according to scans, but shows up on a special PSMA PET scan. They must be on hormone therapy or have had surgery to lower testosterone and have a rising PSA level indicating the cancer is growing despite treatment.

Inclusion Criteria

My testosterone levels are very low due to treatment or surgery.

You must agree and sign a form that explains the study before you can join.

My bone marrow is functioning well.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 7.4 GBq (+/- 10%) of AAA617 once every 6 weeks for 6 cycles

36 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• AAA617
• ARPI

Trial Overview The study tests AAA617 alone and combined with ARPI drugs in men whose prostate cancer can be seen on a PSMA PET scan but not regular imaging. It checks if these treatments can control the cancer without it appearing elsewhere in the body.

How Is the Trial Designed?

Group I: Arm B Experimental Treatment 6 Interventions

Participants will receive 7.4 GBq (+/- 10%) of AAA617 (Lutetium \[177Lu\] vipivotide tetraxetan) once every 6 weeks for 6 cycles. In addition of SOC (ADT plus choice of ARPI as per physician's decision), Best supportive care is allowed.

Group II: Arm A Experimental Treatment 5 Interventions

Participants will receive 7.4 GBq (+/- 10%) of AAA617 (Lutetium \[177Lu\] vipivotide tetraxetan) once every 6 weeks for 6 cycles. ADT must be ongoing; Best supportive care is allowed.

AAA617 is already approved in United States, European Union for the following indications:

Approved in United States as Pluvicto for:

• Prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC)

Approved in European Union as Pluvicto for:

• Prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC)

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

Published Research Related to This Trial

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]

Pluvicto (lutetium Lu 177 vipivotide tetraxetan) is the first FDA-approved targeted radioligand therapy for metastatic castration-resistant prostate cancer (mCRPC), specifically for patients with high levels of prostate-specific membrane antigen (PSMA).

This treatment works by binding to PSMA, which is overexpressed in prostate cancer cells, allowing targeted radiation to damage DNA and induce cell death, making it a promising option in precision medicine for individualized cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lutetium Lu 177 vipivotide tetraxetan for prostate cancer. Liu, X., Fang, GC., Lu, H., et al.[2023]

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]

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]

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]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.84

Clinical outcomes of lutetium-177-vipivotide tetraxetan in ... In this retrospective study of 177 Lu, we see similar PSA and PSA50 responses to reported trials. However, PFS was shorter, and mortality was higher.

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. 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, ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9099330/

Lutetium Lu 177 Vipivotide Tetraxetan: First Approval - PMC A >50% PSA reduction was seen in 27 of 50 patients (54%); median PSA PFS was 5.6 months and median OS was 15.2 months [35]. The efficacy of lutetium Lu 177 ...

5. 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 ...

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

Lutetium Lu 177 Vipivotide Tetraxetan for Patients with ... The FDA granted approval based on a statistically significant and clinically meaningful improvement in overall survival when 177Lu-PSMA-617 was combined with ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05939414

NCT05939414 | An Open-label Study Comparing Lutetium ... The data generated from this study will provide evidence for the treatment of AAA617 in early-stage prostate cancer patients to control recurrent tumor from ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.TPS431

A phase I/II study of neoadjuvant, intra-arterial ... LUPUS is the first trial investigating (177Lu)Lutetium vipivotide tetraxetan intra-arterial infusion and will help to further evaluate if there is a role for ...