Study Comparing AAA817+ARPI Versus Standard of Care in Adult Participants With PSMA-positive mCRPC

Active:	Yes
Cancer Type:	Prostate Cancer Unknown Primary	NCT ID:	NCT06855277
Trial Phases:	Phase III	Protocol IDs:	CAAA817B12301 (primary) NCI-2025-06540 2024-512340-32 2024-512340-32-00
Eligibility:	18 - 100 Years, Male and Female	Study Type:	Diagnostic
Study Sponsor:	Novartis Pharmaceuticals Corporation
NCI Full Details:	http://clinicaltrials.gov/show/NCT06855277

Summary

The purpose of this study is to determine whether [225Ac]Ac-PSMA-617 (AAA817), given for
up to 6 cycles at a dose of 10 Megabecquerel (MBq) +/- 10%, plus androgen receptor
pathway inhibitor (ARPI), improves the radiographic progression free survival (rPFS)
compared to investigator's choice of standard of care (SOC) (ARPI change or taxane-based
chemotherapy or [177Lu]Lu-PSMA-617 (AAA617)) in adult participants with PSMA-positive
metastatic castration resistant prostate cancer (mCRPC) treated with another ARPI as last
treatment and who have not been exposed to a taxane-containing chemotherapy in the mCRPC
setting nor have received any prior PSMA-targeting radioligand therapy.

Objectives

This is a phase III, open label, multicenter randomized study. The study aims at
evaluating the superiority of 225Ac-PSMA-617 combined with androgen receptor pathway
inhibitor (ARPI) over a change of ARPI or chemotherapy or [177Lu]Lu-PSMA-617 (AAA617) in
prolonging progression free survival (rPFS).

Screening period: At screening, the participants will be assessed for eligibility and
will undergo a positron emission tomography (PET)/computed tomography (CT) scan to
evaluate PSMA positivity. Only participants with PSMA positive cancer and confirmed
eligibility criteria will be randomized.

Participants randomized to the investigational arms will receive up to 6 doses of AAA817
10 Mbq +/- 10% given intravenously with or without an ARPI (oral enzalutamide or oral
abiraterone) per investigator's choice. Treatment with ARPI should continue as per
protocol end of treatment criteria.

Participants randomized to SoC will be treated with an ARPI change (oral enzalutamide or
oral abiraterone) or taxane-based chemotherapy (docetaxel or cabazitaxel) or
[177Lu]Lu-PSMA-617 (AAA617)' per investigator's choice. Treatment with ARPI should
continue as per protocol end of treatment criteria. Treatment duration with taxane-based
chemotherapy or AAA617will depend on the chosen regimen per the investigator's discretion
following local guidelines as per standard of care and product labels and adhere to the
protocol end of treatment criteria.

Supportive care will be allowed in both arms at the discretion of the investigator and
includes available care for the eligible participant according to best institutional
practice for mCRPC treatment, including androgen deprivation therapy (ADT).

Safety will be assessed routinely during the study. Crossover is not allowed among study
arms.

The study will be conducted in the USA among other countries globally.

Treatment Sites in Georgia

University Cancer and Blood Center, LLC - Athens Medical Oncology
3320 Old Jefferson Road
Building 800
Athens, GA 30607
www.universitycancer.com

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