A phase II study of niraparib (N), abiraterone acetate (AA) plus prednisone (P) for Hispanic/Latino (HL) and non-Hispanic Black (NHB) patients with metastatic hormone sensitive prostate cancer (mHSPC) and deleterious homologous recombination repair alterations (HRRa; HARMONY).
Background: Patients with prostate cancer and deleterious HRRa have poorer prognosis but derive benefit from poly (ADP-ribose) polymerase (PARP) inhibition. However, prevalence of HRRa and response to PARP inhibition are less well defined in racial/ethnic minorities. We designed the HARMONY trial to evaluate the efficacy of N/AA/P in HL and NHB patients with mHSPC and deleterious HRRa. Methods: This multicenter, open label, phase II study is open through the Hoosier Cancer Research Network in the United States. The trial enrolls patients who self-identify as HL or NHB and have mHSPC with HRRa including BRCA 1/2, BRIP1, CHEK2, FANCA, PALB2, RAD51B, and/or RAD54L. Eligible patients will have hormone sensitive, treatment naïve or minimally treated prostate cancer (i.e., bicalutamide ≤ 45 days, androgen deprivation therapy [ADT] ± AA plus P ≤ 45 days allowed). Prostate cancer variants, other therapy in mHSPC setting, or symptomatic brain metastases are exclusionary. Enrolled patients will receive 24 weeks (w) of ADT plus N/AA dual action tablet (DAT) plus P, followed by an adaptive approach based on prostate specific antigen (PSA) response. Subjects in Arm A (PSA > 4.0 ng/mL at 24 w) can continue ADT/N/AA/P for max 2 years or stop N and escalate therapy to ADT/AA/P plus 6 cycles of docetaxel followed by standard of care (SOC) therapy. Subjects in Arm B (PSA ≤ 4.0 ng/mL at 24 w) will continue ADT/N/AA/P for a total of 12 months. At 12 months in Arm B, subjects with PSA ≥ 0.2 ng/mL will continue ADT/N/AA/P for max 2 years, and subjects achieving PSA < 0.2 ng/mL have the option to continue ADT/N/AA/P for max 2 years or discontinue all therapy with the option to start SOC treatment at disease progression. PSA decline to < 0.2 ng/mL at 24w (primary endpoint) will be evaluated for each racial/ethnicity group against a historic rate of 50%. Thirty patients per racial/ethnic cohort will give 80% power at 0.1 significance to determine noninferiority with a no-inferiority margin of 0.185. Estimating 5% drop out, 64 patients will be enrolled (n=32 HL and n=32 NHB). Key secondary/exploratory endpoints include PSA reduction ≥ 90%, overall response rate, PSA/radiographic progression free survival, overall survival, time to subsequent anti-cancer therapy, quality of life and safety. Key genomic correlatives will be evaluated. ClinicalTrials.gov: NCT06392841. Study support of drug and funding: Janssen Scientific Affairs LLC.
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