Preliminary results from TRITON2: a phase 2 study of rucaparib in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) assoc...

Date 21 October 2018
Event ESMO 2018 Congress
Session Poster Discussion session - Genitourinary tumours, prostate
Topics Anticancer Agents
Prostate Cancer
Presenter Wassim Abida
Citation Annals of Oncology (2018) 29 (suppl_8): viii271-viii302. 10.1093/annonc/mdy284
Authors W. Abida1, A.H. Bryce2, N.J. Vogelzang3, R.J. Amato4, I. Percent5, J.D. Shapiro6, R. McDermott7, A. Hussain8, A. Patnaik9, D. Petrylak10, C.J. Ryan11, T. Stanton12, J. Zhang13, A.D. Simmons14, D. Despain15, M. Collins16, T. Golsorskhi17, H.I. Scher1, S. Chowdhury18
  • 1Genitourinary Oncology, Memorial Sloan Kettering Cancer Center, 10065 - New York/US
  • 2Hematology/oncology, Mayo Clinic, 85054 - Phoenix/US
  • 3Medical Oncology, Comprehensive Cancer Centers of Nevada, 89169 - Las Vegas/US
  • 4Oncology, UT Health Science Center, 77030 - Houston/US
  • 5Medical Oncology, Florida Cancer Specialists, Port Charlotte/US
  • 6Medical Oncology, Cabrini Hospital, 3186 - Malvern/AU
  • 7Genito-urinary Oncology, Adelaide and Meath Hospital (Incorporating the National Children's Hospital), 24 - Dublin/IE
  • 8Department Of Medicine, University of Maryland Greenebaum Cancer Center, Baltimore/US
  • 9Medical Oncology, University of Chicago Comprehensive Cancer Center, 60637 - Chicago/US
  • 10Medical Oncology, Yale University, Yale Cancer Center, 06520-8032 - New Haven/US
  • 11Department Of Medicine, University of Minnesota, Minneapolis/US
  • 12Medical Oncology, St. Joseph Health Cancer Center, Santa Rosa/US
  • 13Genitourinary Oncology, H. Lee Moffitt Cancer Center, Tampa/US
  • 14Translational Medicine, Clovis Oncology, Inc., 94158 - Boulder/US
  • 15Biostatistics, Clovis Oncology, Inc., Boulder/US
  • 16Study Operations, Clovis Oncology, Inc., Boulder/US
  • 17Clinical Development, Clovis Oncology, Inc., Boulder/US
  • 18Medical Oncology, Guy's Hospital and Sarah Cannon Research Institute, SE1 9RT - London/GB

Abstract

Background

Treatment options for mCRPC following androgen deprivation and taxane therapy are limited. Preclinical and limited clinical data suggest efficacy of PARP inhibition in HRR-deficient PCa.

Methods

TRITON2 (NCT02952534; target enrolment, 157 pts) is evaluating rucaparib 600 mg BID in pts with a deleterious germline or somatic alteration in BRCA1, BRCA2 or 1 of 13 other prespecified HRR genes. Pts who progressed on 1–2 lines of androgen receptor–directed therapy and 1 prior line of taxane-based chemotherapy for mCRPC are eligible. The primary endpoint is centrally assessed confirmed objective response rate per modified RECIST v1.1/PCWG3 for pts with measurable disease and confirmed prostate-specific antigen (PSA) response (≥50% decrease) in pts without measurable disease. PSA response in all pts is a secondary endpoint.

Results

At the 6 Mar 2018 data cutoff date, 52 pts were treated with rucaparib. Median duration of follow-up was 3.7 mo (range, 1.0–12.6). Twenty-six pts (50%) had a BRCA1/2 alteration (BRCA pts), 12 had a CDK12 alteration, 10 had an ATM alteration and 4 had an alteration in another HRR gene. Prior therapies included docetaxel (88.5%), enzalutamide (82.7%), abiraterone (71.2%) and cabazitaxel (11.5%). Forty-four pts (84.6%) had bone metastases; 33 (63.5%) and 17 pts (32.7%) had nodal and visceral metastases, respectively. Among BRCA pts, 21 (80.8%) remain on study (median treatment duration, 16.1 wk; range, 4.1–36.9). Eleven of 23 evaluable BRCA pts had a confirmed PSA response (47.8%; 95% CI, 26.8–69.4). Five of 11 evaluable BRCA pts had a confirmed investigator-assessed RECIST/PCWG3 response (45.5%; 95% CI, 16.7–76.6). Overall, the most common treatment-emergent adverse events (TEAEs) included nausea (48.1%; grade ≥3, 3.8%) and asthenia/fatigue (44.2%; grade ≥3, 1.9%). One (1.9%) pt discontinued due to a TEAE; no deaths were reported.

Conclusions

Rucaparib has encouraging antitumour activity in mCRPC pts with a deleterious alteration in BRCA1 or BRCA2. Updated data from current and newly enrolled pts will be presented, including from pts with other gene alterations.

Clinical trial identification

NCT02952534.

Legal entity responsible for the study

Clovis Oncology, Inc.

Funding

Clovis Oncology, Inc.

Editorial Acknowledgement

Writing and editorial support, funded by Clovis Oncology, Inc. (Boulder, CO, USA) was provided by Nathan Yardley, PhD, and Shannon Davis of Ashfield Healthcare Communications (Middletown, CT, USA).

Disclosure

W. Abida: Consulting, Advisory role: Clovis Oncology; Honoraria: Caret Healthcare; Research funding: AstraZeneca, Zenith Epigenetics. N.J. Vogelzang: Consulting, Advisory role: Caris, Sanofi Aventis, Bayer, Pfizer, Janssen, AstraZeneca, Astellas; Stock options owner: Caris; Editor: Up-To-Date. R.J. Amato: Consulting, Advisory role, Speaker bureaus: Jansen, Astellas/Pfizer (Medivation), Novartis. A. Hussain: Consulting, Advisory role: Bayer, Bristol-Myers Squibb, AstraZeneca. A. Patnaik: Consulting, Advisory role: Janssen; Research funding: Bristol-Myers Squibb, GlaxoSmithKline. D. Petrylak: Consulting, Advisory role: Bayer, Bellicum Pharmaceuticals, Dendreon, Johnson & Johnson, Exelixis, Ferring, Millenium, Medivation, Pfizer, Roche, Sanofi and Tyme Pharmaceuticals; Expert testimony: Celgene, Sanofi; Research funding: Oncogenex, Progenics, Johnson & Johnson, Dendreon, Sanofi, Endocyte, Genentech, Merck, Astellas Medivation, Novartis, Agensys, AstraZeneca, Bayer, Lilly, Innocrin Pharma, MedImmune, Millineum, Pfizer, Roche, Sotio; Stock owner, Other ownership interests: Bellicum Pharmaceuticals and Tyme, Inc. C.J. Ryan: Consulting, Advisory role: Bayer, Millennium; Honoraria: Janssen Oncology, Astellas Pharma; Research funding: BIND Biosciences, Karyopharm Therapeutics, Novartis. J. Zhang: Consulting, Advisory role, Speaker’s bureaus: AstraZeneca, Sanofi; Research funding: AstraZeneca, Astellas Pharma, Bayer. A.D. Simmons, D. Despain, M. Collins, T. Golsorskhi: Employee, Stock owner, Stock option owner: Clovis Oncology. H.I. Scher: Consulting, Advisory role: AstraZeneca, Astellas Pharma, Bristol-Myers Squibb, Celgene, Endocyte, Exelixis, Endo Pharmaceuticals, Ferring, Foundation Medicine, Genentech, Janssen, OncologySTAT, Palmetto GBA, Pfizer, Sanofi, Takeda, Ventana Medical Systems, BIRB-Copernicus Group, Medivation; Speaker’s bureau: WebMD; Travel, accommodation: Exelixis, Janssen, Sanofi, Endocyte, AstraZeneca, Genentech, Bristol-Myers Squibb, Celgene, Pfizer, Takeda, Ferring, WIRB-Copernicus Group, and Astellas Pharma; Honoraria: Chugai Pharma; Research funding: BIND Biosciences, Exelixis, Janssen, Medivation, Janssen Diagnostics. S. Chowdhury: Consulting, Advisory role, Speaker’s bureaus: Clovis Oncology, Sanofi, Pfizer, Astellas Pharma, Janssen; Honoraria: GlaxoSmithKline, Novartis; Research funding: Sanofi, Johnson & Johnson. All other authors have declared no conflicts of interest.