1662TiP - HARMONY: A phase II study of niraparib (N)/abiraterone acetate (AA) plus prednisone (P) for Hispanic/Latino (HL) and non-Hispanic Black (NHB) patients (pts) with metastatic hormone sensitive prostate cancer (mHSPC) and deleterious homologous recombination repair alterations (HRRa)

Background

While racial/ethnic disparities in incidence and outcomes have been noted among HL and NHB versus non-Hispanic White pts diagnosed with prostate cancer (PC), enrollment of racial/ethnic minorities onto clinical trials has been a challenge. We designed the HARMONY trial to evaluate the efficacy of targeted, adaptive approaches in HL and NHB pts with mHSPC and deleterious HRRa.

Trial design

In this multisite, phase 2, open-label trial run through the Hoosier Cancer Research Network in the USA, subjects will receive ADT + N/AA plus P for 24 weeks (w), after which they proceed to an adaptive approach: 1) pts with prostate specific antigen (PSA) > 4.0 ng/mL (Cohort A) have option to continue ADT + N/AA plus P for max 2 years or stop N and add docetaxel (6 cycles) to ADT + AA plus P, followed by standard of care (SOC) tx; or 2) pts achieving PSA ≤ 4.0 ng/mL (Cohort B) will continue ADT + N/AA plus P. At 12 months on tx, pts achieving PSA < 0.2 ng/mL have the option to continue ADT + N/AA plus P for max 2 years or discontinue all tx and monitor, with option to start SOC tx at disease progression. Main inclusion criteria are self-identified HL or NHB, mHSPC (minimal treatment i.e., bicalutamide ≤ 45 days, ADT +/- AA plus P ≤ 45 days allowed), and HRRa including BRCA 1/2, BRIP1, CHEK2, FANCA, PALB2, RAD51B, and/or RAD54L. Main exclusion criteria are PC variants (predominant neuroendocrine/small cell carcinoma), other tx in mHSPC setting, or symptomatic brain metastases. Estimating 5% drop out, 32 HL and 32 NHB pts will be enrolled (total n=64). PSA decline to <0.2 ng/mL at 24w (primary endpoint) will be evaluated for each ethnicity group against a historic rate of 0.5, which gives 80% power at 0.1 significance to determine non-inferiority with a non-inferiority margin of 0.185. Key secondary/exploratory endpoints include overall survival, objective response rate, progression free survival (PSA and radiographic), time to subsequent anti-cancer therapy, and safety. Key genomic and quality of life correlatives will be included.

Clinical trial identification

NCT06392841.

Editorial acknowledgement

Legal entity responsible for the study

Hoosier Cancer Research Network.

Funding

Janssen Scientific Affairs, LLC.

Disclosure

Q. Qin: Financial Interests, Personal, Invited Speaker, honorarium: MJH Life Sciences; Financial Interests, Personal and Institutional, Speaker, Consultant, Advisor, and research funding, Site-PI: Exelixis; Financial Interests, Institutional, Research Funding, site-PI: Bristol Myers Squibb. K. Courtney: Financial Interests, Personal, Speaker, Consultant, Advisor: Novartis; Financial Interests, Institutional, Research Funding: Astellas Pharma, Lilly, Stemline Therapeutics, Clovis Oncology, Exelixis, Amgen, Harpoon Therapeutics, Pfizer, Surface Oncology, Myovant Sciences, Celgene/Bristol-Myers Squibb, AstraZeneca, Janssen Research & Development; Financial Interests, Personal, Royalties, Spouse/immediate family member: Athena Diagnostics, Inc. E. Heath: Financial Interests, Personal, Other, Consulting/Advisory Role, Paid Travel: Astellas; Financial Interests, Personal, Advisory Board: AstraZeneca, Bayer, Janssen; Financial Interests, Personal, Other, Paid Travel: Caris Life Science; Financial Interests, Personal, Advisory Board, Speaker's Bureau, Paid Travel: Sanofi; Financial Interests, Personal, Advisory Board, Paid Travel: Seattle Genetics; Financial Interests, Institutional, Local PI: Arvinas, Astellas, AstraZeneca, Bayer, BioXcel, Bristol Myers Squibb, Calibr, Calithera, Corcept, Daiichi Sankyo, Eisai, Five Prime, Fortis, Gilead Sciences, GSK, Harpoon, Hoffman-La Roche, Infinity, Janssen, Merck, Merck Sharpe Dohme, Mirati, Modra, Novartis, Peloton, Pfizer, Pharmacyclics, iTeos, POINT Biopharma; Financial Interests, Personal, Other, Executive Committee Member Precision Oncology Alliance: Caris Life Science; Financial Interests, Institutional, Coordinating PI: Exelixis, Oncolys; Financial Interests, Personal, Steering Committee Member: Seattle Genetics. T. Zhang: Financial Interests, Personal, Advisory Board: Merck, Exelixis, Sanofi-Aventis, Janssen, AstraZeneca, Pfizer, Amgen, BMS, Pharmacyclics, Seagen, QED Therapeutics, Eisai, Aveo, Bayer, Eli Lilly, Gilead, Novartis, EMD Serono; Financial Interests, Personal, Other, Consulting: MJH Associates, Vanaiam, Aptitude Health, PeerView, Clinical Care Options; Financial Interests, Institutional, Local PI: Novartis, AbbVie, AstraZeneca, Pfizer, Astellas, Eli Lilly, Tempus, ALX Oncology, Janux Therapeutics, OncoC4; Financial Interests, Institutional, Steering Committee Member: Merck; Financial Interests, Institutional, Coordinating PI: Janssen, Exelixis; Non-Financial Interests, Advisory Role, Medical Steering Committee: Kidney Cancer Association; Non-Financial Interests, Advisory Role, Scientific Advisory Board: KCCure; Non-Financial Interests, Advisory Role: Myrovlytis Trust. All other authors have declared no conflicts of interest.