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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care

1678 - Interim Results of a Phase 1b Study of Niraparib plus Androgen Receptor-Targeted Therapy in Men with Metastatic Castration-Resistant Prostate Cancer

Date

22 Oct 2018

Session

Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care

Topics

Cytotoxic Therapy

Tumour Site

Prostate Cancer

Presenters

Fred Saad

Citation

Annals of Oncology (2018) 29 (suppl_8): viii271-viii302. 10.1093/annonc/mdy284

Authors

F. Saad1, K.N. Chi2, N. Shore3, J.N. Graff4, E.M. Posadas5, S. Freeman6, J. Tryon7, G.C. Trudel6, J. de Jong8, J. Meltzer9, X. Zhao10, N. Tran6, A. Rezazadeh11

Author affiliations

  • 1 Urology, Centre Hospitalier de l’Universite de Montréal, H2X 0A9 - Montreal/CA
  • 2 Medical Oncology, British Columbia Cancer Agency, V5Z 4E6 - Vancouver/CA
  • 3 Urology, Carolina Urologic Research Center, 29572 - Myrtle Beach/US
  • 4 Hematology And Medical Oncology, Knight Cancer Institute, Oregon Health and Science University, 97239 - Portland/US
  • 5 Medicine, Cedars-Sinai Medical Center, 90048 - Los Angeles/US
  • 6 Clinical Oncology, Janssen R&D, 90024 - Los Angeles/US
  • 7 Clinical Oncology, Janssen R&D, 08869 - Raritan/US
  • 8 Clinical Pharmacology, Janssen R&D, 92121 - San Diego/US
  • 9 Clinical Biostatistics, Janssen R&D, 08869 - Raritan/US
  • 10 Clinical Biostatistics, Janssen R&D, 94080 - San Francisco/US
  • 11 Norton Cancer Institute, Norton Healthcare, 40202 - Louisville/US
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Resources

Abstract 1678

Background

Niraparib is a potent inhibitor of poly (ADP-ribose) polymerase (PARP)-1 and PARP-2, enzymes involved in DNA repair. PARP-1 is involved in modulating androgen receptor (AR) signaling and function. A phase 1b study (Bedivere) of niraparib + AR-targeted therapy (ART), which combines 1000 mg abiraterone acetate and 10 mg prednisone (AA-P), in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) who failed ≥1 line of chemotherapy and ART is ongoing.

Methods

The objectives of this multicenter, open-label study were to establish the recommended phase 2 dose (RP2D) of niraparib and to evaluate the safety and pharmacokinetics (PK) of niraparib + ART. A standard 3 + 3 design was used in part 1, followed by niraparib dose expansion in part 2 with the RP2D of niraparib + AA-P. Pts received niraparib 200 or 300 mg once daily + AA-P. Dose-limiting toxicities (DLTs) were evaluated during the first cycle (28 days).

Results

At data cutoff, 16 pts were treated; 12 at 200 mg and 4 at 300 mg niraparib + AA-P. Median age was 62 years (49–81), median PSA was 70.0 ng/mL (2.7–766.9) and median treatment duration was 3.0 months (0.4–6.6). Most pts (11/16) are still on treatment. No DLT was observed with niraparib 200 mg + AA-P. Two pts had grade 4 neutropenia with niraparib 300 mg + AA-P. Niraparib 200 mg + AA-P is selected as the RP2D to be evaluated in part 2. Preliminary PK data (n = 6) suggest the absence of significant interaction between niraparib and AA-P; systemic exposure of the 2 drugs was comparable to that observed with respective monotherapies. At the RP2D (200 mg + AA-P), most common adverse events (AEs) were nausea (5/12, 41.7%), constipation, vomiting, fatigue and back pain (4/12, 33.3% each); serious AEs (SAEs) included nausea and vomiting (1/12, 8.3% each). In the 200 mg cohort, 10 pts (83.3%) had AEs; 1 pt (8.3%) had an SAE. AEs leading to dose interruption/reduction occurred in 3 pts (25%); 2 pts (16.7%) discontinued treatment due to AEs.

Conclusions

Data to date from the Bedivere study support safety and tolerability of a combination of niraparib 200 mg + AA-P in pts with mCRPC. A future phase 3 clinical study will be needed to assess the clinical benefit of the combination in mCRPC pts with DNA repair gene defects.

Clinical trial identification

NCT02924766 First posted: October 5, 2016.

Legal entity responsible for the study

Janssen Research & Development.

Funding

Janssen Research & Development.

Editorial Acknowledgement

Medical writing assistance was provided by Tracy T. Cao, PhD of Janssen Global Services, LLC and was funded by Janssen Global Services, LLC.

Disclosure

F. Saad: Honoraria: Astellas, AstraZeneca, Bayer, Janssen, Sanofi; Consulting or advisory role: Astellas, AstraZeneca, Bayer, Janssen, Sanofi; Research funding: Janssen, Astellas, Sanofi, Bayer, AstraZeneca, Bristol-Myers Squibb. K.N. Chi: Honoraria, consulting, advisory role, research funding: Janssen. N. Shore: Research funding: AbbVie, Amgen, Astellas, AstraZeneca, Bayer, Clovis, Dendreon, Ferring, GHI, Innocrin, Inovio, Invitae, Merck, Myriad, Janssen, Pfizer, Sanofi-Genzyme; Consulting, advisory role: AbbVie, Amgen, Astellas, AstraZeneca, Bayer, Clovis, Dendreon, Ferring, GHI, Innocrin, Inovio, Invitae, Merck, Myriad, Janssen, Pfizer, Sanofi-Genzyme. J.N. Graff: Honoraria, travel, accommodations, expenses: Janssen, Astellas, Sanofi, Bayer; Research funding: Janssen, Astellas, Merck, Sanofi. E.M. Posadas: Consulting, advisory role: Genentech; Speakers' bureau: Bayer; Research funding: Pfizer; Travel, accommodations, expenses: Tracon. S. Freeman: Consulting: Janssen. J. Tryon, J. de Jong, X. Zhao, N. Tran: Employee: Janssen; Stock: Johnson & Johnson. G.C. Trudel: Employee: Janssen; Stock: Johnson & Johnson. J. Meltzer: Employee, contractor: Janssen; Stock: Johnson & Johnson. A. Rezazadeh: Consulting, advisory role: AstraZeneca, Exelixis, Novartis, Pfizer; Speakers' bureau: Janssen, Astellas, Exelixis, Genentech, AstraZeneca, Bristol-Myers Squibb, Novartis, Amgen, Pfizer, Sanofi; Research funding: Janssen, Medivation, Exelixis, Genentech, AstraZeneca, Bristol-Myers Squibb, Bayer, Macrogenics, Eisai, Bioclin, Clovis; Travel, accommodations, expenses: Janssen, Astellas, Exelixis, Genentech, AstraZeneca, Bristol-Myers Squibb, Novarits, Amgen, Pfizer, Sanofi.

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