Tesaro presents Phase 1 GARNET data of TSR-042 in MSI-H endometrial cancer
Tesaro summarized updated Phase 1 GARNET data of TSR-042 in patients with recurrent or advanced microsatellite instability high endometrial cancer during the European Society for Medical Oncology Congress. Blinded, pooled interim safety data from the Phase 3 PRIMA trial of niraparib in patients with first-line ovarian cancer regardless of biomarker status were also presented in a poster discussion session and additional data from the QUADRA trial of niraparib for treatment of late-line ovarian cancer beyond BRCAmut were presented in a poster display. GARNET is a multicenter, open-label, Phase 1 dose-escalation study designed to assess the safety, pharmacokinetics, pharmacodynamics, and clinical activity of TSR-042 in patients with advanced solid tumors. The weight-based dose escalation and fixed-dose safety portions of the GARNET study have been completed. The ongoing cohort expansion portion of GARNET is evaluating TSR-042 at a dose of 500 milligrams every 3 weeks for the first 4 cycles, and 1000 milligrams every 6 weeks thereafter in four cohorts: MSI-H endometrial cancer, MSI-H non-endometrial cancer, MSS endometrial cancer and non-small cell lung cancer. Data presented at ESMO included safety and efficacy data from the cohort of patients with MSI-H endometrial cancer. At the time of data cutoff, 35 patients with MSI-H endometrial cancer had received treatment with TSR-042. Median duration of response was not reached. Preliminary safety findings among the 35 MSI-H endometrial patients indicate TSR-042 is generally well-tolerated. The data support the unique and convenient dose of TSR-042 of 500 mg Q3W for the first 4 doses, then 1000 mg Q6W thereafter. At this dose, TSR-042 maintained serum concentrations required to retain maximum receptor occupancy throughout the dosing cycle. The GARNET study is intended to support a Biologics License Application submission to the U.S. Food and Drug Administration in 2019. PRIMA is a double-blind, randomized Phase 3 study designed to evaluate niraparib versus placebo as maintenance therapy in first-line ovarian cancer patients. The trial remains blinded for efficacy and safety. The findings presented were from evaluable patients with greater than or equal to 30 days of safety data from blinded pooled niraparib and placebo and indicate improved tolerability with niraparib at the individualized starting dose. TEAEs grade greater than or equal to 3 were lower in the individualized dosing group as compared with the group that received a fixed starting dose of 300 mg of niraparib or placebo. There were fewer dose reductions and dose discontinuations in patients treated with the individualized starting dose compared with the fixed starting dose. TEAEs leading to treatment discontinuation remained low for both groups at 7.9% for the fixed starting dose and 5.3% for the individualized starting dose group. QUADRA, a single arm study, was conducted to assess the activity of ZEJULA monotherapy in the fourth-line or later treatment of patients with ovarian cancer, regardless of platinum sensitivity or biomarker status. Niraparib treatment demonstrated durable clinical activity in late-line patients with BRCAmut tumors, with an ORR of approximately 30%, including patients with platinum-sensitive, -resistant, and -refractory disease, and a median duration of response of 9.2 months. The clinical benefit rate at 16 weeks and 24 weeks were 56% and 38%, respectively. A gradient of clinical activity based on platinum sensitivity was demonstrated in the BRCAmut patient population, with greatest activity demonstrated in patients with platinum-sensitive disease, mOS was not reached. However, even patients with platinum-resistant and platinum-refractory disease experienced benefit from niraparib treatment with ORR of 33% and 19%, and mOS of 26.0 and 23.3 months, respectively. Clinical benefit of niraparib extended beyond patients with BRCA mutations in this late-line setting. Patients with non-BRCAmut/HRDpos platinum-sensitive disease had an ORR of 20%. In total, the biomarker-driven population included 98 patients with ORR of 26%, mDOR of 8.3 months, and a mOS of 23.3 months. The safety profile in the QUADRA treatment study was consistent with the safety profile observed in the NOVA maintenance population.