Clinical trial NCT06780670: Open-label Study Comparing AAA817 Versus Standard of Care in the Treatment of Previously Treated PSMA-positive mCRPC Adults Who Have Disease Progressed on or After [177Lu]Lu-PSMA Targeted Therapy
Official title: PSMAcTION: A Phase II/III, Open-label, International, Multicenter, Randomized Study of AAA817 Versus Standard of Care in the Treatment of Adult Participants With PSMA Positive Metastatic Castration-resistant Prostate Cancer Who Progressed on or After [177Lu]Lu-PSMA Targeted Therapy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Prostate Cancer
Keywords: post [177Lu]Lu-PSMA targeted therapy
PSMA-positive
mCRPC adults
Metastatic castration-resistant prostate cancer
AAA817
[225Ac]Ac-PSMA-617
PSMA-based targeted therapy
Standard of Care
SOC
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2025-01-17
Enrollment: 432
Sex: MALE
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Phase II/III study. Patient population is adult participants with PSMA-positive mCRPC who had treatments with androgen receptor pathway inhibitor (ARPI) and taxane-based chemotherapy and progressed on or after \[177Lu\]Lu-PSMA targeted therapy.

Treatment of interest: the investigational treatment is AAA817 regardless of subsequent anti-neoplastic treatment. The control treatment is investigator's choice of Standard of Care, regardless of subsequent anti-neoplastic treatment

Detailed description: Study CAAA817A12201 consists of 2 parts: a randomized, open-label, international, multicenter, phase II study (Phase II) to collect more information to support the proposed dose of AAA817 and a randomized, open-label, international, multicenter, 2- arm phase III study (Phase III) aimed to evaluate the efficacy and safety of proposed dose of AAA817 vs. investigator's choice of standard of care (SoC) in the treatment of adult participants with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) who had treatments with ARPI and taxane-based chemotherapy, and progressed on or after \[177Lu\]Lu-PSMA targeted therapy. The purpose of the phase II part (Phase II) of this study is to collect additional information to support proposed phase III dose of AAA817.

Eligibility criteria: Inclusion Criteria: ∙

* adults ≥ 18 years of age.
* ECOG performance status of 0 to 2.
* histopathological and/or cytological confirmation of adenocarcinoma of the prostate.
* PSMA-positive disease as assessed by PSMA PET/CT scan using an approved PSMA imaging agent as protocol instructed,
* castrate level of serum/plasma testosterone (\< 50 ng/dL or \< 1.7 nmol/L).
* Prior treatments with an androgen receptor pathway inhibitor (ARPI) and taxane-based chemotherapy, and progressed on or after \[177Lu\]Lu-PSMA targeted therapy.
* ≥ 1 metastatic lesion that is present on screening/baseline CT, MRI, or bone scan imaging obtained ≤ 28 days prior to randomization
* eGFR as requested by the sponsor

Exclusion Criteria:

* Any investigational agents within 28 days prior to the day of randomization.
* Any 225Ac-based investigational compound used prior to the day of randomization.
* Participants with a history of CNS metastases who are neurologically unstable, symptomatic, or receiving corticosteroids for the purpose of maintaining neurologic integrity.
* Concurrent acute kidney injury (renal failure developed between 48 hours to 7 days) or chronic kidney disease (at least 3 months of ongoing renal injury)
* Baseline xerostomia ≥ Grade 2 by CTCAE v.5
* History of uncontrolled hypertension, myocardial infarction (MI), angina pectoris, or coronary artery bypass graft (CABG) within 6 months prior to ICF signature and/or clinically active significant cardiac disease
* History of lymphoproliferative disease or any known malignancy or history of malignancy of any organ system within the past 5 years (except for basal cell carcinoma or actinic keratosis that have been treated with no evidence of recurrence in the past 3 months, non-invasive malignant colon polyps that have been removed).

Other protocol-defined inclusion/exclusion criteria may apply.

Primary outcomes:
measure: Biochemical response rate (Phase II)
timeFrame: from date of randomization up to approximately 24 months
measure: Adverse Events (AEs) and Serious Adverse Events (SAEs), and deaths - Phase II
timeFrame: from day of randomization to 30 days after End of Treatment or (last AAA817 dose date + 55 days, last dose date of SoC + 30 days), whichever is later
measure: Tolerability of the proposed dose of AAA817- Phase II
timeFrame: From on-treatment period which start from the first dose of study treatment until 30 days post-last dose date for SoC and 55 days post last-dose for AAA817
measure: Radiographic progression-free survival (rPFS)- Phase III
timeFrame: from date of randomization up to approximately 24 months
measure: Overall survival (OS)- Phase III
timeFrame: from date of randomization up to approximately 24 months
Secondary outcomes:
measure: Radiographic progression-free survival (rPFS)- Phase II
timeFrame: from date of randomization up to approximately 24 months
measure: Progression free survival (PFS)- Phase II
timeFrame: from date of randomization up to approximately 24 months
measure: Overall response rate (ORR)- Phase II
timeFrame: from date of randomization up to approximately 24 months
measure: Disease control rate (DCR)- Phase II
timeFrame: from date of randomization up to approximately 24 months
measure: Overall survival (OS)- Phase II
timeFrame: from date of randomization up to approximately 24 months
measure: Progression free survival (PFS) -Phase III
timeFrame: from date of randomization up to approximately 24 months
measure: Overall response rate (ORR)- Phase III
timeFrame: from date of randomization up to approximately 24 months
measure: radiographic progression-free survival- Phase III
timeFrame: from date of randomization up to approximately 24 months
measure: Disease control rate (DCR) -Phase III
timeFrame: from date of randomization up to approximately 24 months
measure: Duration of response (DoR)- Phase III
timeFrame: from date of randomization up to approximately 24 months
measure: Time to first radiographic soft tissue progression (TTSTP)- Phase III
timeFrame: from date of randomization up to approximately 24 months
measure: First symptomatic skeletal event (TTSSE)_Phase III
timeFrame: from date of randomization up to approximately 24 months
measure: Prostate specific antigen (PSA) response -Phase III
timeFrame: from date of randomization up to approximately 24 months
measure: Patient reported disease related symptoms and health-related quality of life (HRQoL): Phase III
timeFrame: from date of randomization up to approximately 24 months
measure: Patient-reported pain severity: Phase III
timeFrame: from date of randomization up to approximately 24 months
Other outcomes:
Locations:
city: Singapore
country: Singapore
facility: Novartis Investigative Site
Study officials:
References: