Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2017

The TRITON clinical trial programme: evaluation of the PARP inhibitor rucaparib in patients with metastatic castration-resistant prostate cancer (mCRPC) associated with homologous recombination deficiency (HRD) (#263)

Laurence Krieger 1 , Jeremy Shapiro 2 , Ian Byard 3 , David Campbell 4 , Timothy Clay 5 , Vinod Ganju 6 , Simon Watkins 7 , Andy Simmons 7 , Jowell Go 7 , Sanjay Shetty 7 , Tony Golsorkhi 7 , Wassim Abida 8 , Charles J. Ryan 9 , Howard I. Scher 8 , Simon Chowdhury 10
  1. Northern Cancer Institute, St Leonards, NSW, Australia
  2. Cabrini Hospital, Malvern, VIC, Australia
  3. Royal Hobart Hospital, Hobart, TAS, Australia
  4. University Hospital Geelong (Barwon Health), Geelong, VIC, Australia
  5. St. John of God Hospital Subiaco, Subiaco, WA, Australia
  6. Peninsula & Southeast Oncology, Frankston, VIC, Australia
  7. Clovis Oncology, Inc., Boulder, CO, USA
  8. Memorial Sloan Kettering Cancer Center, New York, NY, USA
  9. UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA
  10. Guy’s Hospital & Sarah Cannon Research Institute, London, UK


Poly(ADP-ribose) polymerase (PARP) inhibitors have demonstrated preliminary evidence of antitumour activity in patients with mCRPC and a homologous recombination (HR) gene mutation (Mateo et al. N Engl J Med. 2015;373:1697-708). These data provide a compelling rationale for evaluating rucaparib in patients with mCRPC associated with HRD.


TRITON2 (NCT02952534) is a phase 2 study evaluating rucaparib (600 mg BID) in patients (n≈160) with mCRPC harbouring a deleterious germline or somatic BRCA1, BRCA2, or ATM mutation (by local and/or central testing). An exploratory cohort will enrol patients with an alteration in any of 12 other prespecified HR genes (eg, RAD51C, RAD51D, or PALB2). Patients must have progressed on androgen receptor (AR) signalling–directed therapy and 1 prior taxane-based chemotherapy for mCRPC. The primary endpoint of TRITON2 is response rate (per modified RECIST v1.1/PCWG3 in patients with soft-tissue disease and prostate-specific antigen response in patients with nonmeasurable disease).

TRITON3 (NCT02975934) is a randomised phase 3 study evaluating rucaparib vs physician’s choice of abiraterone, enzalutamide, or docetaxel in patients (n≈400) with mCRPC harbouring a deleterious germline or somatic BRCA1, BRCA2, or ATM mutation (by local and/or central testing). Patients must have progressed on AR signalling–directed therapy for mCRPC; prior chemotherapy for mCRPC or prior PARP inhibitor treatment are exclusions. Patients 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 (per modified RECIST v1.1/PCWG3).

Pretreatment blood samples collected from all patients in both trials will enable development of a plasma-based companion diagnostic to select patients for rucaparib treatment.


The TRITON programme is actively recruiting and will assess the efficacy and safety of rucaparib treatment in patients with mCRPC associated with HRD.