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) 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.
Additional locations may be listed on ClinicalTrials.gov for NCT06855277.
See trial information on ClinicalTrials.gov for a list of participating sites.
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 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) per
investigator's choice. Treatment with ARPI should continue as per protocol end of
treatment criteria. Treatment duration with taxane-based chemotherapy will 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.
Lead OrganizationNovartis Pharmaceuticals Corporation