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

Novartis

Status and phase: Begins enrollment in 3 months; Phase 3

Conditions: Prostate Cancer

Treatments: Drug: AAA817; Drug: Standard of Care; Drug: ARPI

Study type: Interventional

Funder types: Industry

Identifiers

NCT06855277

CAAA817B12301

2024-512340-32-00 (Registry Identifier)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 486 estimated patients

Sex: Male

Ages: 18 to 100 years old

Volunteers: No Healthy Volunteers

Inclusion and 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 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).

Key Exclusion Criteria:

• Previous treatment with any approved or investigational RLT, approved or investigational radioisotopes
• Previous treatment with any conventional external beam radiotherapy including hemi-body radiation within 6 weeks of randomization (within 2 weeks for radiotherapy of localized metastases).
• Participants with known or suspected deleterious germline or somatic homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer.
• Any approved or investigational agents/systemic anti-cancer therapy (e.g. other chemotherapy, investigational therapy, immunotherapy or biological therapy including monoclonal antibodies) within 28 days (or 5 times the half-life of that therapy whichever is longer) of the anticipated day C1D1.
• Diagnosed with other active malignancies that are expected to alter life expectancy or may interfere with disease assessment.

Other protocol-defined inclusion/exclusion criteria may apply.

Trial design

Primary purpose: Diagnostic

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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486 participants in 3 patient groups

Investigational Arm: AAA817+ARPI (enzalutamide or abiraterone)

Experimental group

Description:

Participants will receive AAA817 infusion directly into a vein with ARPIs.

Treatment:

Drug: ARPI

Drug: AAA817

Investigational Arm: AAA817

Experimental group

Description:

Participants will receive AAA817 infusion directly into a vein.

Treatment:

Drug: AAA817

Control arm: Investigator's choice of SoC (ARPI or taxane-based chemotherapy)

Active Comparator group

Description:

Participants will receive standard treatment as decided by the trial doctor either as a chemotherapy infusion directly into a vein or ARPI either as capsules or tablets.

Treatment:

Drug: ARPI

Drug: Standard of Care