Positive results from phase III PRIME study of Zejula at Society of Gynecologic Oncology Meeting – Zai Lab + GSK

Zai Lab Limited presented data from the Phase III PRIME study of Zejula (niraparib) as maintenance therapy at the Society of Gynecologic Oncology annual meeting . Zejula demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) with a tolerable safety profile in Chinese patients with newly diagnosed advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer (collectively termed as ovarian cancer) following a response to platinum-based chemotherapy, regardless of biomarker status.

In the PRIME study, median PFS was significantly longer for patients treated with niraparib compared to placebo: 24.8 months versus 8.3 months, hazard ratio (HR), 0.45; p<0.001.

Other pre-specified efficacy results included : i. gBRCAmut patients: mPFS, not reached vs. 10.8 months; HR and 95% CI: 0.40 (0.23, 0.68); ii. Non-gBRCAmut patients: mPFS, 19.3 months vs. 8.3 months; HR and 95% CI: 0.48 (0.34, 0.67); iii. Overall survival data are still immature (percentage of death in niraparib and placebo groups are 14.5% vs. 21.7%); there is a trend in favor of niraparib at the data cut-off.

The PRIMA study previously conducted by Zai Lab’s partner GlaxoSmithKline plc (GSK) demonstrated that niraparib conferred a PFS benefit to patients with advanced ovarian cancer after a response to first-line platinum-based chemotherapy compared with placebo, regardless of biomarker status. An individualized starting dosing (ISD) based on baseline bodyweight and platelet count to personalize treatment of niraparib was used in approximately 35% of patients in PRIMA. The starting dose was individualized at 200 mg except for those patients with a baseline body weight greater than 77kg and a platelet count greater than 150K/uL, in which case the starting dose was 300 mg.

The current PRIME study was designed to prospectively assess the efficacy and safety of niraparib with this ISD as maintenance therapy in patients with newly diagnosed advanced ovarian cancer after a response to first-line platinum-based chemotherapy, regardless of biomarker status and postoperative residual disease status.

In PRIME, the safety profile of niraparib was improved with the ISD (individualized starting dosing) prospectively applied to all patients. Based on the prospective ISD with niraparib, less than 7% of patients discontinued treatment due to adverse events, the lowest rate of any PARPi Phase III first-line maintenance ovarian cancer trial. Compared with previous fixed starting dose, the ISD reduced the incidence of hematological treatment-emergent adverse events (TEAEs). Grade greater than 3 hematological TEAEs of neutrophil count decrease, anemia, and platelet count decrease in patients treated with niraparib versus placebo were 17.3% vs. 1.6%, 18.0% vs. 1.6%, and 14.1% vs. 0.8%, respectively..