Study Comparing AAA817+ARPI Versus Standard of Care in Adult Participants With PSMA-positive mCRPC
Prostate Cancer
Unknown Primary
18 - 100 Years, Male and Female
CAAA817B12301 (primary)
NCI-2025-06540
2024-512340-32
2024-512340-32-00
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.
Eligibility
- 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
Treatment Sites in Georgia
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