Date: 2017-09-11
Type of
information: Presentation of results at a congress
phase: 1-2
Announcement: presentation of results at the European Society for Medical Oncology (ESMO) 2017 Congress
Company: Tesaro (US - MA)
Product: niraparib in combination with pembrolizumab
Action
mechanism:
- poly ADP ribose polymerase PARP inhibitor/PARP inhibitor/monoclonal antibody/immune checkpoint inhibitor. Niraparib is an orally administered poly polymerase (PARP) inhibitor, currently in late-stage development for patients with metastatic breast cancer and ovarian cancer. PARP proteins play a key survival role in DNA repair in cancer cells. By inhibiting PARP, certain defective cancer cells are not able to repair themselves, leading to cell death. A portion of men with prostate cancer have these defective cancer cells and may benefit from use of a PARP inhibitor, either alone, or in combination with other treatments.
- Keytruda® (pembrolizumab - MK-3475) is an highly selective monoclonal anti-PD-1 antibody designed to restore the natural ability of the immune system to recognize and target cancer cells by selectively achieving dual ligand blockade (PD-L1 and PD-L2) of the PD-1 protein. By blocking PD-1, pembrolizumab enables activation of the immune system’s T-cells that target cancer by essentially releasing a brake on the immune system.
Disease: triple-negative breast cancer orovarian Cancer
Therapeutic
area: Cancer - Oncology
Country: USA
Trial
details:
Latest
news:
- • On September 11, 2017, Tesaro provided a summary of Zejula® data presented at the 2017 European Society of Medical Oncology (ESMO) Annual Meeting in Madrid. Preliminary Phase 2 niraparib/pembrolizumab combination (TOPACIO) data shows activity in patients with platinum-resistant ovarian and triple-negative breast cancer
Data from a Phase 1 dose-escalation study of niraparib in combination with pembrolizumab in patients with platinum-resistant ovarian cancer (OC) or triple negative breast cancer (TNBC) was presented, along with preliminary response data from patients thus far treated in the Phase 2 TOPACIO study. In Phase 1, among the nine evaluable OC patients, five responded (partial or complete response) and four achieved stable disease. Three of the five responders had tumors that tested as wildtype BRCA 1/2 and three as PD-L1 negative (<1%). Of the four evaluable TNBC patients, three had stable disease and one patient came off study prior to her first assessment. The most common treatment related grade ?3 adverse events occurring in ?2 patients included anemia (35.7%), thrombocytopenia (35.7%), neutropenia (14.3%) and decreased platelet counts (14.3%). The recommended Phase 2 dose of niraparib was established as 200 mg oral niraparib once daily (increasing to 300 mg after cycle 2 in patients with no significant hematologic toxicities) in combination with 200 mg IV pembrolizumab on day 1 of each 21-day cycle.
- The Phase 2 portion of the TOPACIO study is ongoing, and, as of the data cutoff, 36 OC patients and 47 TNBC patients were enrolled out of a planned 48 patients for each tumor cohort. Twenty-nine OC and 27 TNBC patients have been assessed by at least one scan with responses observed in both BRCA wild-type and PD-L1 negative tumors. Among the patients who had received at least one on-study scan, 6 OC patients and 5 TNBC patients had a ?30% decrease in tumor lesion size and 10 of these 11 patients continue on therapy. Overall 52% OC and 63% TNBC patients who did not have progressive disease continue on therapy. No new safety signals were identified, and less than 7% of Phase 2 patients had experienced grade ?3 thrombocytopenia during the first treatment cycle. Thirty patients (36.1%) enrolled in Phase 2 reported treatment-related grade ?3 adverse events including anemia (8.4%), fatigue (6.0%), platelet count decrease (6.0%) and thrombocytopenia (6.0%).
Is
general: Yes
