AAA817 + ARPI for Prostate Cancer

(AcTFirst Trial)

Recruiting at 23 trial locations

Overseen By Novartis Pharmaceuticals

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: Novartis Pharmaceuticals

Must be taking: Androgen receptor inhibitors

Must not be taking: Radioisotopes, Chemotherapy

Disqualifiers: Neuroendocrine, HRR mutations, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 7

Duration: Up to 48 weeks

605 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a new treatment, AAA817, combined with an existing therapy (androgen receptor pathway inhibitor, ARPI), can slow the progression of prostate cancer that has spread and resists standard hormone treatments. It compares this new approach to usual care, which may include different hormone therapies or chemotherapy. Men with prostate cancer unresponsive to hormone therapy and who haven't received this type of chemotherapy before might be suitable candidates. The goal is to determine if the new treatment can more effectively stall cancer growth. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants a chance to contribute to a treatment that could soon become widely available.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have had certain treatments like chemotherapy or radiotherapy recently. 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 shows that AAA817, also known as \[225Ac\]Ac-PSMA-617, is under study for treating advanced prostate cancer. This treatment targets prostate cancer cells and releases radiation to destroy them. Although its safety is not fully confirmed, early studies have shown promise. However, complete safety information for AAA817 alone is not yet available.

When combined with drugs like enzalutamide or abiraterone, which slow or stop prostate cancer growth, these medications are generally well-tolerated. Past research indicates that patients using these drugs have a median survival of over three years. This suggests some level of safety when combined with AAA817, but the full safety details of this combination remain under investigation. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about AAA817 for prostate cancer treatment because it offers a novel approach compared to traditional therapies. Unlike standard options like ARPIs and taxane-based chemotherapy, AAA817 is administered directly into the vein, potentially providing more targeted delivery to cancer cells. Additionally, when combined with ARPIs such as enzalutamide or abiraterone, it may enhance the effectiveness of the treatment by using a dual mechanism to attack the cancer. This unique method has the potential to improve outcomes for patients who may not respond well to existing treatments.

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

Research shows that AAA817 targets a protein called PSMA on prostate cancer cells. It attaches to these cells and releases radiation to destroy them. In early studies, patients responded well to AAA817, particularly those with prostate cancer resistant to standard hormone treatments that has spread to other parts of the body. In this trial, some participants will receive AAA817 alone, while others will receive it in combination with ARPIs like enzalutamide or abiraterone, which block hormones that help cancer grow. Previous studies have shown that patients taking these hormone-blocking drugs lived for an average of 36.1 to 39.9 months. This suggests that adding AAA817 might improve these results by directly attacking the cancer cells. ^{1 2 4 5 6}

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 with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) who have previously been treated with ARPI but not taxane chemotherapy in the mCRPC setting. They must be able to perform daily activities (ECOG 0-2), have confirmed adenocarcinoma of the prostate, and show disease progression on a PSMA-PET scan.

Inclusion Criteria

I have signed the consent form to participate in the study.

I can care for myself and am up and about more than 50% of my waking hours.

My prostate cancer is confirmed to be adenocarcinoma without neuroendocrine features.

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 up to 6 doses of AAA817 10 Mbq +/- 10% intravenously with or without an ARPI, or standard of care treatment with ARPI change or taxane-based chemotherapy

Up to 48 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

40 months

What Are the Treatments Tested in This Trial?

Interventions

• AAA817
• ARPI

Trial Overview [225Ac]Ac-PSMA-617 (AAA817) combined with an androgen receptor pathway inhibitor (ARPI) is being tested against standard care options. The study aims to see if AAA817 improves survival without disease worsening when given for up to six cycles at specified doses alongside ARPI.

How Is the Trial Designed?

Group I: Investigational Arm: AAA817+ARPI (enzalutamide or abiraterone) Experimental Treatment 2 Interventions

Participants will receive AAA817 infusion directly into a vein with ARPIs.

Group II: Investigational Arm: AAA817 Experimental Treatment 1 Intervention

Participants will receive AAA817 infusion directly into a vein.

Group III: Control arm: Investigator's choice of SoC (ARPI or taxane-based chemotherapy) Active Control 2 Interventions

Participants will receive standard treatment as decided by the trial doctor either as a chemotherapy infusion directly into a vein or ARPI either as capsules or tablets.

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. clinicaltrials.gov clinicaltrials.gov/study/NCT06855277

NCT06855277 | Study Comparing AAA817+ARPI Versus ... AAA817 is being studied for treating PSMA positive mCRPC. Inside the body, it attaches itself to PSMA on the cell surface of the prostate cancer cells and emits ...

2. novartis.com novartis.com/clinicaltrials/study/nct06780670

Open-label Study Comparing AAA817 Versus Standard of ... All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06780670

NCT06780670 | Open-label Study Comparing AAA817 ... Study CAAA817A12201 consists of 2 parts: a randomized, open-label, international, multicenter, phase II study (Phase II) to collect more information to support ...

4. novartis.com novartis.com/clinicaltrials/study/nct06855277

Study Comparing AAA817+ARPI Versus Standard of Care ... AAA817 is being studied for treating PSMA positive mCRPC. Inside the body, it attaches itself to PSMA on the cell surface of the prostate cancer cells and emits ...

5. withpower.com withpower.com/trial/phase-2-and-3-prostatic-neoplasms-3-2025-38299

AAA817 for Prostate Cancer (PSMAcTION Trial) This Phase II/III trial aims to determine if AAA817 can provide better outcomes than existing treatment options. How Is the Trial Designed? 4Treatment groups.

6. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/568576

Open-label Study Comparing AAA817 Versus Standard of ... This is a Phase II/III study. Patient population is adult participants with PSMA-positive mCRPC who had treatments with androgen receptor pathway inhibitor ...