Home › Trials › NCT06855277

AAA817 (225Ac-PSMA-617) plus ARPI versus standard care for PSMA-positive metastatic castration-resistant prostate cancer

A Phase III, Open-label, Multi-center, Randomized Study Comparing AAA817+ARPI Versus Standard of Care in Adult Participants With PSMA-positive Metastatic Castration Resistant Prostate Cancer

PHASE3 · Novartis · NCT06855277

This trial tests whether adding [225Ac]Ac-PSMA-617 (AAA817) to an androgen receptor pathway inhibitor helps people with PSMA-positive metastatic castration-resistant prostate cancer stay free of radiographic progression longer than standard treatment options.

Quick facts

PhasePHASE3
Study typeInterventional
Enrollment940 (estimated)
Ages18 Years to 100 Years
SexMale
SponsorNovartis (industry)
Drugs / interventionschemotherapy, immunotherapy, radiation
Locations55 sites (Santa Barbara, California and 54 other locations)
Trial IDNCT06855277 on ClinicalTrials.gov

What this trial studies

This is a phase III, open-label, randomized multicenter trial enrolling adults with PSMA-PET positive metastatic castration-resistant prostate cancer who received an ARPI as their most recent therapy. Participants are randomized to receive up to six intravenous cycles of AAA817 (10 MBq ±10%) with or without an ARPI, versus investigator's choice standard of care (ARPI change, taxane chemotherapy, or [177Lu]Lu-PSMA-617). PSMA PET/CT is required at screening to confirm PSMA-positive disease, and key eligibility excludes prior PSMA-targeted radioligand therapy or taxane use in the mCRPC setting. The primary efficacy endpoint is radiographic progression-free survival (rPFS).

Who should consider this trial

Good fit: Adults (≥18) with PSMA-PET positive metastatic castration-resistant prostate cancer, ECOG 0–2, who had an ARPI as their last treatment and have not received taxane chemotherapy for mCRPC or prior PSMA-targeted radioligand therapy.

Not a fit: Patients with non-PSMA-expressing disease, mixed neuroendocrine histology, prior PSMA radioligand therapy, or prior taxane use in the mCRPC setting are unlikely to benefit from this regimen.

Why it matters

Potential benefit: If successful, the combination could extend the time patients live without radiographic progression and provide a new PSMA-targeted alpha-emitter treatment option.

How similar studies have performed: Randomized trials have demonstrated benefit for [177Lu]Lu-PSMA-617, and smaller early-phase reports suggest promising activity for 225Ac-PSMA-617, but phase III evidence for the alpha-emitter approach is still limited.

Eligibility criteria

Show full inclusion / exclusion criteria 
Key Inclusion Criteria:

* Signed informed consent must be obtained prior to participation in the study.
* Participants must be adults ≥ 18 years of age.
* Participants must have an ECOG performance status of 0 to 2.
* Participants must have histological, and/or cytological confirmation of adenocarcinoma of the prostate. Participants with mixed histology (neuroendocrine) are not eligible.
* Participants who have received taxane-based chemotherapy in mHSPC setting are eligible if they are deemed appropriate for chemotherapy, ARPI change or AAA617 as the next line of therapy in the opinion of the Investigator. Note: Participants who have received taxane-based chemotherapy for mCRPC are excluded.
* Participants must not have received taxane-based chemotherapy in mCRPC setting (allowed in mHSPC setting).
* Participants must have PSMA-PET positive disease using a PSMA imaging agent that is approved as per protocol.
* Participant must have been diagnosed with mCRPC with documented progressive disease while on treatment with ARPI in mHSPC or earlier setting as their last treatment (and did not progress on more than one ARPI).

  * Participants with deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer, as per local testing, may be enrolled if they had prior exposure to PARPi.

Key Exclusion Criteria:

* Previous anti-cancer treatment with any approved or investigational radiopharmaceuticals (for example, \[177Lu\]Lu-PSMA, \[177Lu\]-DOTA, or Radium- 223.)
* Previous treatment with any external beam radiotherapy including hemi-body radiation within 6 weeks of randomization (within 2 weeks for radiotherapy of localized metastases).

  * Any prior PARP inhibitor or other systemic anticancer therapy administered for metastatic castration-resistant prostate cancer (mCRPC). Any other approved or investigational systemic therapy (including chemotherapy, immunotherapy, biologics, or monoclonal antibodies) is prohibited within 28 days or 5 half-lives (whichever is shorter) before randomization.

Note: Prior ARPI administered in the mHSPC setting or earlier may continue until C1D1.

Other protocol-defined inclusion/exclusion criteria may apply.

Where this trial is running

Santa Barbara, California and 54 other locations

+5 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.

View on ClinicalTrials.gov →

Conditions: Prostate Cancer, Positive Metastatic Castration Resistant Prostate Cancer, PSMA, PSMA-positive, AAA817, [225AC] AC-PSMA-617, Radioligand Therapy, RLT

Last reviewed 2026-05-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.