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
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 details:
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
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
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).
Eligibility
Age eligible for study : NA
Healthy volunteers accepted : No
Gender eligible for study: ALL
Things to know
Study dates
Study start:
Primary completion:
Study completion finish:
Study type
TREATMENT
Phase
- PHASE2PHASE3
Study ID
NCT06780670
Intervention or treatment
DRUG: Investigators choice of SoC
DRUG: AAA817
DRUG: AAA817
DRUG: AAA817
Conditions
- Prostate Cancer
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Research sites nearby
Closest Location:
Novartis Investigative Site
Select from list below to view details:
Novartis Investigative Site
Darlinghurst, New South Wales, Australia
Novartis Investigative Site
Herston, Queensland, Australia
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Who is running the clinical trial?
Novartis Pharmaceuticals
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
| Participant Group/Arm | Intervention/Treatment |
|---|---|
EXPERIMENTAL: Phase II: AAA817 Dose B
| Drug: AAA817 |
ACTIVE_COMPARATOR: Phase III: Investigator's choice of SoC
| Drug: Investigators choice of SoC |
EXPERIMENTAL: Phase II: AAA817 Dose A
| Drug: AAA817 |
EXPERIMENTAL: Phase III: Recommended Phase 3 Dose of AAA817
| Drug: AAA817 |
What is the study measuring?
Primary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 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 | 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 | 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 | 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 | from date of randomization up to approximately 24 months |
Secondary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| 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 | from date of randomization up to approximately 24 months |
| Progression free survival (PFS)- Phase II | Percentage of Participants meeting Progression Free Survival | 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) | 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 | 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 | 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 | 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) | 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) | 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. | 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 | 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 | 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 | 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) | 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). | from date of randomization up to approximately 24 months |
References
Clinical Trials Gov: 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 TherapyOther trials to consider
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