The STAMPEDE2 niraparib-abiraterone acetate + prednisolone trial: A phase III, randomised, open-label trial in patients with metastatic prostate cancer (mPC) with a deleterious alteration in a homologous recombination repair (HRR) gene starting androgen deprivation therapy (ADT)

BackgroundTreatment intensification at the start of ADT improves overall survival (OS) in mPC. Up to 15% of mPC harbour a deleterious alteration in BRCA2 or a related HRR gene that confers sensitivity to polyadenosine diphosphate-ribose polymerase inhibitors. STAMPEDE2 will test for benefit from Niraparib-Abiraterone Acetate + Prednisolone in HRR-altered mPC starting ADT.Trial designSTAMPEDE2 is a phase III, randomised, open label, multi-centre platform protocol testing treatments in metastatic hormone sensitive prostate cancer (NCT06320067, ISRCTN66357938). For the Niraparib-Abiraterone Acetate + Prednisolone trial, patients identified as biomarker positive (HRR gene alteration) on clinical next-generation tumour sequencing are offered randomisation 1:1 to either arm A (standard of care with physician’s choice androgen receptor signalling inhibitor [SoC ARSI]) or arm N (standard of care with Niraparib-Abiraterone Acetate + Prednisolone) (Table). Prior randomisation into the STAMPEDE2 SABR or PSMA-Lutetium trials is allowed. Randomisation is stratified by planned use of Docetaxel and/or prostate radiotherapy (RT) and/or SABR/PSMA-Lutetium. Target recruitment is 680 patients with the primary outcomes Overall Survival (OS). Target HR=0.65, 80% power. The Niraparib-Abiraterone Acetate + Prednisolone trial is a collaboration with Janssen Pharmaceutica NV, sponsored by University College London (UCL), and co-ordinated by the MRC CTU at UCL. Table: 1656TiP Key exclusion criteria >6 months ADT Evidence of PSA progression on ADT +/- ARSI Interventions Arm A: SoC ARSI Arm N: ADT + 2 regular-strength dual-action tablets 100 mg Niraparib/500mg Abiraterone Acetate per tablet (total dose 200 mg Niraparib/1000 mg Abiraterone Acetate) + Prednisolone 5mg OD Arms A&N: +/- Docetaxel +/- Prostate RT +/- SABR +/- PSMA-Lutetium Treat until radiographic progression, unacceptable toxicity or death Primary endpoints OS Secondary endpoints Radiographic progression free survival Failure free survival Prostate cancer specific survival Toxicity Quality of life Cost-effectiveness Clinical trial identificationNCT06320067, ISRCTN66357938.Legal entity responsible for the studyUniversity College London.FundingJanssen.DisclosureL.C. Brown: Financial Interests, Institutional, Research Grant, £170k educational grant for the FOCUS4-C Trial from June 2017 to Dec 2021: AstraZeneca; Financial Interests, Institutional, Funding, Various grants awarded to my institution for work undertaken as part of the STAMPEDE Trial: janssen pharmaceuticals; Financial Interests, Institutional, Funding, Grant funding to my institution for the STAMPEDE2 trial.: Novartis AAA; Non-Financial Interests, Other, I am a member of the CRUK CERP funding advisory panel and my Institution also receive grant funding from CRUK for the STAMPEDE and FOCUS4 trials: Cancer Research UK. W. Cross: Financial Interests, Personal, Speaker, Consultant, Advisor: AAA Novartis, Bayer, Janssen, Astellas, Ipsen, Myriad Genetics, Allied Healthcare. M.K. Parmar: Financial Interests, Institutional, Full or part-time Employment, Director at MRC Clinical Trials Unit at UCL: Medical Research Council Clinical Trials Unit at UCL; Financial Interests, Personal and Institutional, Research Grant: AstraZeneca, Astellas, Janssen, Baxter, GSK; Financial Interests, Institutional, Research Grant: Clovis, Abcodia Pvt Ltd., Akagera, Amgen, Aspirin Foundation, Bayer, BMS US, Bri-BioCepheid, Cipla, CSL Behring, Eli Lilly, Emergent Biosolutions, Gilead Sciences, Grifols, Johnson & Johnson, Pfizer, Sanofi, ViiVHealthcare, Micronoma, Modus Theraputics, Mylan, Serum Institute of India, shionogi, SyntenyBiotechnology, Takeda, Tibotec, Transgene, Virco and Xenothera; Non-Financial Interests, Advisory Role, Euro Ewing Consortium: University College London; Non-Financial Interests, Advisory Role, rEECur: University of Birmingham; Non-Financial Interests, Advisory Role, CompARE Trial: University of Birmingham; Non-Financial Interests, Advisory Role, ROSSINI Trial Platform: University of Birmingham. N.D. James: Financial Interests, Personal, Advisory Board, Advice around PARP inhibitors: AstraZeneca; Financial Interests, Personal, Advisory Board, Prostate cancer therapies: Janssen, Clovis, Novartis; Financial Interests, Institutional, Advisory Board, Assisted with submissions regarding licencing for abiraterone: Janssen; Financial Interests, Personal, Advisory Board, Docetaxel: Sanofi; Financial Interests, Institutional, Advisory Board, Providing STAMPEDE trial data to facilitate licence extensions internationally for docetaxel: Sanofi; Financial Interests, Personal, Advisory Board, Bladder cancer therapy: Merck; Financial Interests, Personal, Advisory Board, Advice around novel hormone therapies for prostate cancer: Bayer; Financial Interests, Personal, Invited Speaker, Lecture tour in Brazil August 2022 - speaking on therapy for advanced prostate cancer: Merck Sharp & Dohme (UK) Limited; Financial Interests, Institutional, Coordinating PI, Funding for STAMPEDE trial: Janssen, Astellas; Financial Interests, Institutional, Coordinating PI, Funding for RADIO trial bladder cancer: AstraZeneca. G. Attard: Financial Interests, Personal, Invited Speaker: Janssen, Astellas, AstraZeneca; Financial Interests, Personal, Advisory Board: Janssen, Astellas, Novartis, Bayer, AstraZeneca, Pfizer, Sanofi, Sapience, Orion, Novartis, Blue Earth Therapeutics; Financial Interests, Personal, Royalties, Included in list of rewards to discoverers of abiraterone: Institute of Cancer Research; Financial Interests, Institutional, Advisory Board: Artera, Veracyte; Financial Interests, Institutional, Research Grant: Janssen, Astellas, Novartis; Financial Interests, Institutional, Coordinating PI: Janssen; Financial Interests, Institutional, Local PI: Novartis, Pfizer; Non-Financial Interests, Principal Investigator: Janssen, Astellas; Non-Financial Interests, Advisory Role: Janssen, AstraZeneca; Non-Financial Interests, Project Lead: Artera, Veracyte. All other authors have declared no conflicts of interest.