GSK's Zejula-Jemperli Combo Meets Endpoint but Falls Short on Survival in Ovarian Cancer

GSK has released results from its Phase 3 FIRST trial, assessing the efficacy of a combination treatment involving Zejula and Jemperli for first-line advanced ovarian cancer. The trial’s primary endpoint, progression-free survival, showed a statistically significant improvement when Jemperli was added to chemotherapy and Zejula maintenance, both with or without the addition of bevacizumab. Hesham Abdullah, GSK's Senior Vice President and Global Head of Oncology R&D, emphasized the company’s commitment to exploring treatments for gynecological cancers and expressed anticipation for sharing the complete trial findings.

Despite the success in meeting the primary endpoint, the trial fell short on a critical secondary endpoint: overall survival. GSK acknowledged that this aspect did not achieve statistical significance and mentioned that further analyses are being conducted. The company plans to share the collected data with regulatory authorities for further examination.

During the course of the trial, there was a significant modification in its design. Initially, participants were divided into three groups: one receiving chemotherapy followed by a placebo, another receiving chemotherapy followed by Zejula maintenance, and a third group receiving chemotherapy and Jemperli followed by maintenance with both Zejula and Jemperli. However, after Zejula gained approval in 2020 for use in the first-line setting, the trial design was altered to focus on the latter two groups, eliminating the chemotherapy and placebo cohort. This change reflects the evolving landscape of cancer treatment and the need to adapt clinical trials to incorporate newly approved therapies.

In 2023, Zejula generated approximately $650 million in revenue for GSK, underscoring its importance in the company’s oncology portfolio. Jemperli, which was initially approved for first-line treatment of endometrial cancer in patients with mismatch repair deficiency (dMMR) and microsatellite instability-high (MSI-H), expanded its label in August to include all adult endometrial cancer patients. This PD-1 antibody contributed roughly $177 million to GSK’s revenue in the same year, highlighting its growing role in cancer treatment.

GSK’s ongoing investigations into the Zejula-Jemperli combo reflect a strategic focus on maximizing the potential of these drugs in treating advanced ovarian cancer, a particularly challenging type of cancer with significant unmet medical needs. By continuing to explore the efficacy of this combination, GSK aims to provide new therapeutic options for patients and potentially improve outcomes in this difficult-to-treat cancer.

The trial outcomes have implications for future research and treatment protocols. While the combination has shown promise in improving progression-free survival, understanding its impact on overall survival will be crucial. As GSK proceeds with further analyses and regulatory discussions, the oncology community will be keenly interested in the details that emerge from the complete trial results.

Overall, GSK’s efforts in this trial highlight the complexities of cancer treatment research, where promising results in one area can be tempered by challenges in another. The company remains committed to advancing its research and delivering innovative treatments for patients in need.