Zai Lab: Niraparib Monotherapy Significantly Improves PFS in First-Line Platinum-Responsive Ovarian Cancer Patients

• The PRIMA study, presented at the Presidential Symposium of the 2019 ESMO Annual Congress and simultaneously published in The New England Journal of Medicine, demonstrated that niraparib reduced the risk of disease progression or death by 38% compared with placebo in the overall study population.

• More importantly, both HRD-positive and HRD-negative patients demonstrated clinically and statistically significant clinical benefits.

On September 28, GlaxoSmithKline, a partner of Zai Lab, announced the clinical results from the Phase III randomized, double-blind, placebo-controlled PRIMA study (ENGOT-OV26/GOG-3012). This trial evaluated niraparib as first-line maintenance therapy in patients with ovarian cancer following platinum-based chemotherapy. The results demonstrated that treatment with niraparib reduced the risk of disease progression or death by 38% in the overall population (PFS, HR 0.62; 95% CI, 0.50–0.75; p<0.001).

These results, demonstrating a reduction in the risk of disease progression with clinical significance, included the following types of female patients:

Tumor patients carrying BRCA mutations (60% reduction in progression risk, HR 0.40 (95% CI, 0.27–0.62), p < 0.001)

Homologous Recombination Deficiency (HRD)-Positive Tumors with Wild-Type BRCA (50% Reduction in Risk of Progression, HR 0.50 [95% CI, 0.30–0.83], p=0.006)

HRD-negative tumor patients (32% reduction in progression risk, HR 0.68 [95% CI, 0.49–0.94], p=0.020).

The PRIMA study enrolled patients who responded to platinum-based chemotherapy as first-line treatment, including those at high risk of disease progression—a population with significant unmet needs that has been underrepresented in previous first-line ovarian cancer studies.

In the interim analysis of overall survival (OS), niraparib also demonstrated an encouraging trend toward OS improvement compared with placebo. In the prespecified interim OS analysis, niraparib showed an overall survival benefit across the entire study population (HR 0.70; 95% CI 0.44–1.11). In the HRD-positive subgroup, 91% of patients treated with niraparib were still alive at 24 months, compared with 85% in the placebo group (HR 0.61; 95% CI 0.27–1.40). As these data are not yet mature, their clinical significance remains unclear. The interim OS analysis further revealed that in the HRD-negative subgroup, 81% of patients treated with niraparib were still alive at 24 months, compared with 59% of those receiving placebo (HR 0.51; 95% CI 0.27–0.97).

Dr. Antonio Gonzalez, Principal Investigator of the PRIMA study and Deputy Director of the Department of Medical Oncology at the University of Navarra in Spain, stated, “The PRIMA study demonstrates the importance of maintenance therapy and the benefits of niraparib for patients with ovarian cancer. I believe that single-agent niraparib maintenance therapy following surgery and platinum-based chemotherapy will represent a new treatment option for patients.”

Niraparib is not yet approved for first-line maintenance treatment of ovarian cancer. GSK will share these data with relevant health regulatory authorities and expects to submit the application materials by the end of the year.

The PRIMA study confirmed that the safety profile of niraparib is consistent with previously established data. The most common grade 3 or higher adverse events associated with niraparib include anemia (31%), thrombocytopenia (29%), and neutropenia (13%). Individualized dosing regimens based on body weight and/or platelet count can reduce the incidence of hematologic treatment-emergent adverse events. No new adverse events were identified. Patient-reported outcomes have demonstrated similar quality of life between the niraparib and placebo control groups.

Niraparib is currently marketed in the United States and Europe under the brand name Zejula®.

Zai Lab received approval in October 2018 to market and sell Zejula in Hong Kong, thereafter initiating an aggressive commercialization strategy. In June 2018, niraparib was approved in Macau for the treatment of patients with platinum-sensitive recurrent ovarian cancer. In mainland China, the National Medical Products Administration (NMPA) accepted the new drug application for Zejula on December 12, 2018, and included it in the priority review program on January 28, 2019.

About the PRIMA Study

PRIMA is a double-blind, randomized, Phase III clinical study evaluating niraparib versus placebo as first-line treatment in patients with Stage III or IV ovarian cancer. The study assessed the efficacy of niraparib as maintenance therapy using progression-free survival (PFS) as the endpoint. Platinum-responsive patients were randomized in a 2:1 ratio to receive either niraparib or placebo. The study incorporated an individualized starting dose regimen for niraparib: patients with a baseline body weight <77 kg or a platelet count <150,000/μL received an initial dose of 200 mg/day, while all other patients received 300 mg/day.

About Niraparib

Zeelco (niraparib, ZL2306) is a highly potent and selective, once-daily oral small-molecule inhibitor of poly(ADP-ribose) polymerase 1/2 (PARP1/2). Niraparib was approved in the United States in March 2017 and in Europe in November of the same year for the maintenance treatment of patients with recurrent epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer who have achieved a complete or partial response to platinum-based chemotherapy. Following its approvals in the US and Europe, niraparib received marketing approval in Hong Kong in October 2018. In December 2018, a new drug application for niraparib was submitted to China’s National Medical Products Administration (NMPA), and it was included in the priority review and approval list in January 2019. In June 2019, niraparib became available in Macau.

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