SUMMARY  

• AMPLITUDE (NCT04497844) is an ongoing, phase 3, randomized, double-blind, placebo-controlled, international, multicenter study evaluating the efficacy and safety of AKEEGA with prednisone plus androgen deprivation therapy (ADT) compared to placebo/abiraterone acetate with prednisone (AAP) plus ADT in patients with deleterious germline or somatic homologous recombination repair (HRR) gene-altered mCSPC. The primary endpoint is radiographic progression-free survival (rPFS). The study has a planned enrollment of 788 patients from 352 sites in 32 countries.^1-3 The efficacy and safety results have not been published.
• ProBio (Prostate-Biomarker, NCT03903835) is an an ongoing, phase 3, outcomeadaptive, multiarm, multiple-assignment, randomized, open-label, international biomarker-driven platform study in patients with de novo metastatic hormone-sensitive prostate cancer (mHSPC) or first-line (L1) metastatic castration-resistant prostate cancer (mCRPC). Patients entering in the mHSPC phase will be randomized to receive either standard of care (SOC) or an experimental treatment with androgen receptor signaling inhibitors (ARSi), docetaxel, or AKEEGA with prednisone based on predefined biomarker signatures. The study has a planned enrollment of 750 patients.^4,5 The efficacy and safety results have not been published.

CLINICAL DATA

AMPLITUDE Study

Rathkopf et al (2022)³ described the study design for an ongoing, phase 3, randomized, double-blind, placebo-controlled, multicenter study evaluating the efficacy and safety of AKEEGA with prednisone plus ADT compared to placebo/AAP plus ADT in patients with deleterious germline or somatic HRR genealtered mCSPC.

Study Design/Methods

• The study design is presented in Figure: AMPLITUDE Study Design.

The efficacy and safety results of the AMPLITUDE study have not been published.

ProBio Study

De Laere et al (2022)⁴ described the study design for an ongoing, phase 3, outcomeadaptive, multiarm, multiple-assignment, randomized, open-label, international biomarker-driven platform study in patients with de novo mHSPC or L1 mCRPC. The information summarized below is limited to the de novo mHSPC treatment phase.

Study Design/Methods

• Patients with de novo mHSPC will be randomized to receive either SOC or an experimental treatment with ARSis, docetaxel, or AKEEGA with prednisone. Local therapy to the prostate will be allowed across all treatment arms.
• Patients were stratified by prespecified biomarker signatures (inferred from diagnostic tissue and/or liquid biopsy profiling), previous treatment, and fraction of circulating tumor DNA (ctDNA).
• Key inclusion criteria: ≥18 years old; histologically confirmed prostate adenocarcinoma starting systemic therapy for metastatic disease, including de novo mHSPC; distant metastatic disease documented by positive bone scan or metastatic lesions on computed tomography (CT)/magnetic resonance imaging (MRI); adequate health and hematologic, hepatic, and renal functions, as assessed by investigator; albumin ≥28 g/L; Eastern Cooperative Oncology Group/World Health Organization performance score of 0-2
• Key exclusion criteria: failure to detect ctDNA or somatic alterations in primary tumor biopsies; prior systemic therapy (including ADT); other malignancies within 5 years except nonmelanoma skin cancer; myocardial infarction, unstable angina, angioplasty, bypass surgery, stroke, transient ischemic attack, or New York Heart Association class III or IV congestive heart failure ≤6 months prior to randomization; uncontrolled hypertension
• Primary endpoint: to determine whether a biomarker signature and treatment combination is superior to SOC with respect to progression-free survival (PFS)
• Secondary endpoints: to determine whether biomarker-driven treatment selection can improve PFS for the experimental arms combined vs the control arm and whether a treatment class is superior for a certain biomarker signature by comparing the experimental arms against each other
• Other secondary endpoints: prostate-specific antigen (PSA) PFS, rPFS, response rates, time to second progression (PFS2), overall survival (OS), quality of life, health economics, drug safety, and identification of new biomarkers and superior treatment sequencing regimens

The efficacy and safety results of the ProBio study have not been published.

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File (and/or other resources, including internal/external databases) was conducted on 17 May 2024.