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

Phase 3RecruitingNCT06780670

Novartis Pharmaceuticals443 enrolled

Overview

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

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

443

Conditions

Prostate Cancer

Eligibility

Sex: MALEMin age: 18 YearsMax age: 100 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Biochemical response rate (Phase II)

Biochemical response rate as defined as the percentage of participants who achieved a ≥ 50% decrease from baseline that is confirmed by a second measurement

Time frame: from date of randomization up to approximately 24 months

Adverse Events (AEs) and Serious Adverse Events (SAEs), and deaths - Phase II

Safety defined as the type, incidence and severity of AEs and SAEs, and deaths

Time frame: 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

Tolerability of the proposed dose of AAA817- Phase II

Percentage of participants who experienced Dose interruptions, reductions, discontinuation, dose intensity and duration of exposure

Time frame: 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

Radiographic progression-free survival (rPFS)- Phase III

Percentage of participants who are alive without radiographic progression or who are lost to follow-up at the time of analysis

Time frame: from date of randomization up to approximately 24 months

Overall survival (OS)- Phase III

Percentage of participants who are alive or who are lost to follow-up at the time of analysis

Time frame: from date of randomization up to approximately 24 months

Secondary Outcomes

Radiographic progression-free survival (rPFS)- Phase II

Percentage of participants who are alive without radiographic progression or who are lost to follow-up at the time of analysis

Time frame: from date of randomization up to approximately 24 months

Progression free survival (PFS)- Phase II

Percentage of Participants meeting Progression Free Survival

Time frame: from date of randomization up to approximately 24 months

Overall response rate (ORR)- Phase II

Percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR)

Time frame: from date of randomization up to approximately 24 months

Disease control rate (DCR)- Phase II

Percentage of participants with BOR of CR, PR, stable disease (SD) or non-CR/non-PD

Time frame: from date of randomization up to approximately 24 months

Overall survival (OS)- Phase II

Percentage of participants who are alive or who are lost to follow-up at the analysis data cut-off

Time frame: from date of randomization up to approximately 24 months

Progression free survival (PFS) -Phase III

Percentage of participants with PFS -defined as the time from date of randomization to first documented progression

Time frame: from date of randomization up to approximately 24 months

Overall response rate (ORR)- Phase III

ORR is defined as the percentage of participants with best overall response (BOR) of confirmed complete response (CR) or partial response (PR)

Time frame: from date of randomization up to approximately 24 months

Disease control rate (DCR) -Phase III

DCR is defined as the percentage of participants with BOR of confirmed CR, PR, stable disease (SD) or Non-CR/Non progressive disease (PD)

Time frame: from date of randomization up to approximately 24 months

Duration of response (DoR)- Phase III

Percentage of participants with confirmed DoR defined as duration of time between the date of first documented response (CR or PR) and progression or death due to any cause, whichever occurs first.

Time frame: from date of randomization up to approximately 24 months

Time to first radiographic soft tissue progression (TTSTP)- Phase III

Percentage of participants with confirmed first radiographic progression in soft tissue

Time frame: from date of randomization up to approximately 24 months

First symptomatic skeletal event (TTSSE)_Phase III

Percentage of participants with confirmed skeletal event is defined as new symptomatic pathological bone fracture, spinal cord compression, tumor-related orthopedic surgical intervention, or requirement for radiation therapy to relieve bone pain, or death due to any cause, whichever occurs first

Time frame: from date of randomization up to approximately 24 months

Prostate specific antigen (PSA) response -Phase III

PSA50 is defined as the percentage of participants who achieved a confirmed ≥ 50% decrease from baseline

Time frame: from date of randomization up to approximately 24 months

Patient reported disease related symptoms and health-related quality of life (HRQoL): Phase III

Percentage of participants who had a Change from baseline on FACT-P Prostate Cancer Subscale (PCS)

Time frame: from date of randomization up to approximately 24 months

Time to worsening on the Worst Pain: Phase III

Time to worsening on the Worst Pain defined as the time from randomization to the first occurrence of worsening on the Worst Pain item (brief pain inventory - short form (BPI-SF)) of at least 30% of baseline or minimum of 2 points increase from baseline, or death due to any cause, whichever occurs first. BPI-SF is a self-reported questionnaire to evaluate pain intensity (severity) and impact of pain on the participant's daily functioning (interference).

Time frame: from date of randomization up to approximately 24 months

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

Overview

Conditions

Interventions

Eligibility

Locations (81)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts