A clinical study to learn more about the effects of AAA817 in men with prostate cancer that has progressed after targeted PSMA therapy with [177Lu]Lu-ligands

Zusammenfassung der Studie

The aim of this study is to compare the effect of AAA817 (also known as [225Ac] AcPSMA617) with standard treatment in men with advanced prostate cancer (mCRPC) whose disease has progressed after targeted [177Lu] Lu-PSMA therapy. AAA817 is a targeted cancer treatment that uses specific radiation to attack the PSMA molecule on prostate cancer cells. This study consists of two parts. The researchers will begin with Part A before proceeding to Part B. A minimum of 12 participants is expected for Part A and 420 participants for Part B. Participants have an equal chance of being assigned to Group 1 or Group 2. Switzerland will only participate in Part B of the study. Data from Part A and from an ongoing study with the same investigational product will be combined to confirm the selected dose for Part B of the study. Part B: Researchers will randomly assign participants to one of 2 groups. The probability of participants being assigned to Group 1 is twice that of Group 2. Treatment will last up to 48 weeks. - Group 1: Participants will receive the AAA817 dose as an infusion directly into a vein at a specified interval. - Group 2: Participants will receive a standard treatment selected by the study physician. The study physicians, study staff, and participants will know which treatment participants will receive. The study physicians will monitor the prostate cancer and overall health of participants throughout the study. Participants will return to the study center for follow-up 56 days after receiving the last dose of treatment.

(BASEC)

Untersuchte Intervention

During screening, candidates will be assessed for eligibility and whether they are PSMA-positive by conducting a special PSMA-PET/CT scan. Enrollment in Part B will begin once 12 patients have received at least one dose of AAA817 in Part A.

In Part B, participants randomized to the AAA817 arm will be treated with AAA817 once every 8 weeks. The dose for Part B will be determined based on the detailed data regarding the benefit/risk profile from Part A.

After the dose of AAA817 in Cycle 4 and before the first day of Cycle 5, a special independent committee will evaluate Part B of the study to determine whether the participant meets the following criteria:

- Evidence of partial improvement or stable disease;

- Signs of residual disease on CT with contrast/MRI or bone scan;

- No reasons for discontinuation of treatment;

- Good tolerability of AAA817 treatment.

If the participant meets all of the above criteria and agrees to further treatment with AAA817, the investigator may administer additional treatment cycles. If the participant does not meet all criteria or does not agree to further treatment with AAA817, no further doses of AAA817 will be administered after Cycle 4.

In the control arm, participants will receive the standard treatment selected by the investigator. This may include ARPIs, chemotherapy with taxanes, carboplatin, or radium-223 dichloride. The duration of treatment will depend on the chosen regimen and the investigator's decisions. Efficacy will be assessed through conventional imaging, PSMA-PET/CT scan, and PSA levels. Safety will be regularly monitored throughout the study and during safety and long-term follow-up periods.

The key questions that Part B aims to answer are:

- How long does it take for a participant's cancer to worsen after treatment with AAA817 compared to standard treatment, or until death occurs?

- How long do participants receiving AAA817 live after participating in this study compared to participants receiving standard treatment?

- What medical problems, also known as adverse events, occur during this study?

(BASEC)

Untersuchte Krankheit(en)

metastatic castration-resistant prostate cancer (mCRPC)

(BASEC)

Sponsor

Novartis Pharma Schweiz AG

(BASEC)

Name der bewilligenden Ethikkommission (bei multizentrischen Studien nur die Leitkommission)

Ethikkommission Bern

(BASEC)

Datum der Bewilligung durch die Ethikkommission

15.07.2025

(BASEC)

Ergebnisse der Studie