A phase Ib/II study of niraparib combination therapies for the treatment of metastatic castration-resistant prostate cancer (NCT03431350)
| Autor: | Eugene Zhu, Bernard Doger, Sumit K. Subudhi, Nishi Kothari, Jeffrey J. Tryon, Lawrence Karsh, Deborah Ricci, Xin Zhao, Avivit Peer, Johann S. de Bono, Dana E. Rathkopf, Ana Aparicio, Namphuong Tran, Amado J. Zurita, William Kevin Kelly |
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| Rok vydání: | 2019 |
| Předmět: |
Oncology
Cancer Research medicine.medical_specialty business.industry Castration resistant medicine.disease Clinical trial Rapid identification 03 medical and health sciences Prostate cancer 0302 clinical medicine 030220 oncology & carcinogenesis Internal medicine medicine business 030215 immunology |
| Zdroj: | Journal of Clinical Oncology. 37:TPS5087-TPS5087 |
| ISSN: | 1527-7755 0732-183X |
| Popis: | TPS5087 Background: Assessing multiple therapies in a single clinical trial can facilitate the rapid identification of new agents for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC). Niraparib (Nirap) is a highly selective PARP inhibitor, with potent activity against PARP-1 and PARP-2 deoxyribonucleic acid (DNA)-repair polymerases. PARP inhibition may be especially lethal in tumor cells with genetic DNA damage response deficits (DRD). Based on promising preclinical and clinical data, this study is designed as a master protocol with nirap as a backbone therapy. Combination 1 assesses the safety and efficacy of nirap plus JNJ-63723283 (JNJ-283), an anti-PD-1 monoclonal antibody. Combination 2 assesses nirap plus abiraterone acetate and prednisone (AA-P). Methods: This multicenter, global, open-label study is currently open at 18 sites in 5 countries of the planned XX sites, and is enrolling patients with mCRPC who have progressed on ≥1 androgen-receptor targeted therapy for mCRPC. Enrollment at time of abstract submission was 25 for combination 1. When combined with AA-P, the RP2D has been determined to be nirap 200 mg. The recommended phase-2 dose (RP2D) of nirap plus JNJ-283 was determined in Part 1 based on the incidence of specified adverse events and PK data to be 480 mg every 4 weeks. For Part 2 of the study, patients are assigned to receive oral niraparib daily plus JNJ-283 infusions once every four weeks until disease progression, unacceptable toxicity, death, study termination. Part 2 is described in the table. Clinical trial information: NCT03431350. [Table: see text] |
| Databáze: | OpenAIRE |
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