TESARO Inc. said the QUADRA study of Zejula treatment in heavily pre-treated patients with ovarian cancer achieved the pre-specified primary endpoint and demonstrated Zejula monotherapy activity in a biomarker-selected patient population.
Previous studies have shown PARP inhibitor activity in the late-line treatment of patients with BRCA mutations.
QUADRA, a single arm study (n=461), was conducted to assess the activity of Zejula monotherapy in the fourth-line plus treatment of specific ovarian cancer patient populations. Of the 92% of QUADRA participants who were PARP inhibitor naïve, 15% had a BRCA mutation, over two-thirds were platinum resistant/refractory and 63% had received prior bevacizumab.
Zejula demonstrated activity in the primary efficacy population of fourth and fifth-line HRD positive patients who were PARP inhibitor naïve, and platinum sensitive (n=45), with an objective response rate of 29%, and duration of response of 9.2 months. In patients who were fourth line or greater with BRCA mutations, including platinum-sensitive, resistant and refractory, (n=55), the ORR was 31% and the median DOR was 9.4 months.
At a starting dose of 300 milligrams of Zejula, the most commonly observed adverse events were consistent with prior clinical experience and included myelosuppression, which was generally managed via dose modifications. TESARO intends to discuss a biomarker focused regulatory submission with the FDA for a potential supplemental New Drug Application in the second half of 2018.
Beyond QUADRA, clinical trials of niraparib in ovarian cancer include:
PRIMA: Monotherapy phase III trial for patients with first-line ovarian cancer regardless of biomarker status expected to complete enrollment in Q2 2018; data anticipated in 2019
OVARIO: Combination phase II trial assessing Zejula with bevacizumab for patients with newly diagnosed ovarian cancer
FIRST: Combination phase III clinical trial of chemotherapy ± TSR-042, and Zejula in first-line ovarian cancer to be initiated in 1H 2018