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Poster display session

2788 - The TRITON Clinical Trial Programme: Evaluation of the PARP Inhibitor Rucaparib in Patients (Pts) with Metastatic Castration-Resistant Prostate Cancer (mCRPC) Associated with Homologous Recombination Deficiency (HRD)

Date

10 Sep 2017

Session

Poster display session

Presenters

Simon Chowdhury

Citation

Annals of Oncology (2017) 28 (suppl_5): v269-v294. 10.1093/annonc/mdx370

Authors

S. Chowdhury1, W. Abida2, J. Arranz Arija3, G. Daugaard4, K. Fizazi5, E. Gez6, A. Heidenreich7, F. Joly Lobbedez8, R. McDermott9, A.S. Merseburger10, J.M. Piulats Rodriguez11, B. Sautois12, S. Sridhar13, C.N. Sternberg14, S. Watkins15, A. Simmons16, S. Shetty17, A. Golsorkhi18, C.J. Ryan19, H. Scher2

Author affiliations

  • 1 Urological Cancer, Guy’s Hospital & Sarah Cannon Research Institute, SE1 9RT - London/GB
  • 2 Genitourinary Oncology, Memorial Sloan Kettering Cancer Center, New York/US
  • 3 Medical Oncology, Hospital General Universitario Gregorio Marañon, 28007 - Madrid/ES
  • 4 Oncology, Copenhagen University Hospital, Rigshospitalet, 2100 - Copenhagen/DK
  • 5 Groupe Uro-genitologie, University of Paris Institut Gustave Roussy, 94805 - Villejuif/FR
  • 6 Department Of Oncology, Sourasky Medical Center, 64239 - Tel Aviv/IL
  • 7 Klinik Für Urologie, Universitätsklinikum Köln, 50937 - Köln/DE
  • 8 Medical Oncology, Centre Francois Baclesse, 14076 - Caen/FR
  • 9 Genito-urinary Oncology, Tallaght & St. Vincent’s University Hospital and Cancer Trials Ireland, 24 - Dublin/IE
  • 10 Urologic Oncology, Lübeck University Hospital, Lübeck/DE
  • 11 Medical Oncology, Insitut Catalán d'Oncología, 8907 - Barcelona/ES
  • 12 Medical Oncology, University Hospital of Liege, Liege/BE
  • 13 Medical Oncology, Princess Margaret Hospital, M5G 2M9 - Toronto/CA
  • 14 Department Of Oncology, San Camillo Forlanini Hospital, 156 - Roma/IT
  • 15 Clinical Science, Clovis Oncology, Inc., Boulder/US
  • 16 Translational Medicine, Clovis Oncology, Inc., Boulder/US
  • 17 Clinical Operations, Clovis Oncology, Inc., Boulder/US
  • 18 Clinical Development, Clovis Oncology, Inc., 80301 - Boulder/US
  • 19 Genitourinary Medical Oncology, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco/US
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Resources

Abstract 2788

Background

Recent data show that ≈20% of pts with mCRPC have a germline or somatic alteration in either BRCA1, BRCA2 or ATM (homologous recombination [HR] genes) (Robinson et al. Cell. 2015;161:1215-28), suggesting these molecular markers may be used to select pts with mCRPC for targeted treatment with a poly(ADP-ribose) polymerase inhibitor (PARPi). PARPis have demonstrated preliminary evidence of antitumour activity in pts with sporadic mCRPC and an HR gene mutation (Mateo et al. N Engl J Med. 2015;373:1697-708). These results provide a strong rationale for investigating rucaparib in pts with mCRPC associated with HRD.

Trial design

TRITON2 is a phase 2 study evaluating rucaparib 600 mg BID in pts (n≈160) with mCRPC who have a deleterious germline or somatic BRCA1, BRCA2 or ATM mutation (per local and/or central testing). Pts with tumours with an alteration in any of 12 additional prespecified HR genes (eg, RAD51C, RAD51D or PALB2) may enrol in an exploratory cohort. Pts must have progressed on androgen receptor (AR)-targeted therapy and on 1 prior taxane-based chemotherapy for mCRPC. The primary endpoint of TRITON2 is response rate (modified RECIST v1.1/PCWG3 in soft-tissue disease and PSA response with nonmeasurable disease). TRITON3 is a randomised phase 3 study evaluating rucaparib 600 mg BID vs physician’s choice of treatment (abiraterone, enzalutamide or docetaxel) in pts (n≈400) with mCRPC with a deleterious germline or somatic BRCA1, BRCA2 or ATM mutation (per local and/or central testing). Pts must have progressed on AR-targeted therapy for mCRPC; pts who received prior chemotherapy for mCRPC or PARPi treatment are excluded. Pts will be randomised 2:1 to rucaparib or physician’s choice; the latter group may cross over to rucaparib after radiographic progression confirmed by independent radiology review (IRR). The primary endpoint of TRITON3 is IRR-confirmed radiographic progression-free survival (modified RECIST v1.1/PCWG3 criteria). Pretreatment blood samples will be collected from all pts in both trials to enable development of a plasma-based companion diagnostic that predicts rucaparib sensitivity.

Clinical trial identification

TRITON2 – EudraCT 2016-003162-13, NCT02952534; TRITON3 – NCT02975934

Legal entity responsible for the study

Clovis Oncology, Inc.

Funding

Clovis Oncology, Inc.

Disclosure

S. Chowdhury: Honoraria: GlaxoSmithKline, Novartis Consulting or Advisory Role: Clovis Oncology, Sanofi, Pfizer, Astellas Pharma, Janssen. Speakers' Bureau: Clovis Oncology, Sanofi, Pfizer, Astellas Pharma, Janssen Research Funding: Sanofi, Johnson & Johnson. W. Abida: Consulting or Advisory Role: Clovis Oncology Honoraria: Caret Healthcare Research Funding: AstraZeneca, Zenith Epigenetic. J. Arranz Arija: AdBoard: Astellas, Sanofi, Bayer, Jansen-Cilag. K. Fizazi: Advisory boards: Amgen, Astellas, AstraZeneca, Bayer, CureVac, Essa, Genentech, Janssen, Orion, Sanofi. Honorarium: Amgen, Astellas, AstraZeneca, Bayer, CureVac, Essa, Genentech, Janssen, Orion, Sanofi. A. Heidenreich: Consultant: Astellas, Bayer, IPSEN, sanofi Advisory Board: Amgen, Astellas, Bayer, Ipsen, Jansen, Sanofi. Honoraria: Amgen, Astellas, Bayer, Ferring, IPSEN, Jansen, Pfizer, Sanofi, Takeda Research Grant: Amgen, Astellas, Sanofi. J.M. Piulats Rodriguez: Consultant: Clovis, Astellas, Janssen, Bayer, BMS, MSD, Merck Serono, Pfizer, Roche and Novartis. Research grants: Merck Serono, BMS, Pfizer, Janssen and Astellas. C.N. Sternberg: Honoraria: Janssen, Sanofi, Astellas, Clovis, Bayer, Ferring. Research Funding to institution: Roche/Genentech, Bayer, Sanofi, Janssen, Medivation, Sanofi Genzyme. S. Watkins: Employment: Clovis Oncology Stock. Other ownership interests: Clovis Oncology, United Health Group. A. Simmons: Employment: Clovis Oncology Consulting or Advisory Role: Redwood Bioscience Stock and Other Ownership Interests: Clovis Oncology. S. Shetty, A. Golsorkhi: Employment: Clovis Oncology Stock and Other Ownership Interests: Clovis Oncology. C.J. Ryan: Consulting or Advisory Role: Bayer, Millennium Honoraria: Janssen Oncology, Astellas Pharma Research Funding: BIND Biosciences, Karyopharm Therapeutics, Novartis. H. Scher: Advisory: Endo, Foundation Med, OncologySTAT, Palmetto GBA, Takeda, Ventana Med Sys, MDV Spk Bureau: WebMD Hon: Chugai Consult/Travel: AZ, Astellas, BMS, Celgene, Endocyte, Exelixis, Ferring, GNE, PFE, Sanofi, Janssen, Takeda, WIRBCopernicus Grp. All other authors have declared no conflicts of interest.

Disclosure

S. Chowdhury: Honoraria: GlaxoSmithKline, Novartis Consulting or Advisory Role: Clovis Oncology, Sanofi, Pfizer, Astellas Pharma, Janssen. Speakers\' Bureau: Clovis Oncology, Sanofi, Pfizer, Astellas Pharma, Janssen Research Funding: Sanofi, Johnson & Johnson. W. Abida: Consulting or Advisory Role: Clovis Oncology Honoraria: Caret Healthcare Research Funding: AstraZeneca, Zenith Epigenetic. J. Arranz Arija: AdBoard: Astellas, Sanofi, Bayer, Jansen-Cilag. K. Fizazi: Advisory boards: Amgen, Astellas, AstraZeneca, Bayer, CureVac, Essa, Genentech, Janssen, Orion, Sanofi. Honorarium: Amgen, Astellas, AstraZeneca, Bayer, CureVac, Essa, Genentech, Janssen, Orion, Sanofi. A. Heidenreich: Consultant: Astellas, Bayer, IPSEN, sanofi Advisory Board: Amgen, Astellas, Bayer, Ipsen, Jansen, Sanofi. Honoraria: Amgen, Astellas, Bayer, Ferring, IPSEN, Jansen, Pfizer, Sanofi, Takeda Research Grant: Amgen, Astellas, Sanofi. J.M. Piulats Rodriguez: Consultant: Clovis, Astellas, Janssen, Bayer, BMS, MSD, Merck Serono, Pfizer, Roche and Novartis. Research grants: Merck Serono, BMS, Pfizer, Janssen and Astellas. C.N. Sternberg: Honoraria: Janssen, Sanofi, Astellas, Clovis, Bayer, Ferring. Research Funding to institution: Roche/Genentech, Bayer, Sanofi, Janssen, Medivation, Sanofi Genzyme. S. Watkins: Employment: Clovis Oncology Stock. Other ownership interests: Clovis Oncology, United Health Group. A. Simmons: Employment: Clovis Oncology Consulting or Advisory Role: Redwood Bioscience Stock and Other Ownership Interests: Clovis Oncology. S. Shetty, A. Golsorkhi: Employment: Clovis Oncology Stock and Other Ownership Interests: Clovis Oncology. C.J. Ryan: Consulting or Advisory Role: Bayer, Millennium Honoraria: Janssen Oncology, Astellas Pharma Research Funding: BIND Biosciences, Karyopharm Therapeutics, Novartis. H. Scher: Advisory: Endo, Foundation Med, OncologySTAT, Palmetto GBA, Takeda, Ventana Med Sys, MDV Spk Bureau: WebMD Hon: Chugai Consult/Travel: AZ, Astellas, BMS, Celgene, Endocyte, Exelixis, Ferring, GNE, PFE, Sanofi, Janssen, Takeda, WIRBCopernicus Grp. All other authors have declared no conflicts of interest.

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