At the American Society of Clinical Oncology (ASCO) Annual Meeting 2025, held from 31 May to 3 June in Chicago, Illinois, updated efficacy and safety data from the international, double-blind, randomised Phase III FIRST clinical trial were presented on 1 June. The trial evaluated the combination of GSK’s Jemperli (dostarlimab), a monoclonal antibody targeting programmed cell death protein 1, and Zejula (niraparib), a poly (ADP-ribose) polymerase (PARP) inhibitor, in combination with platinum-based chemotherapy (PtCh) as a first-line therapy in patients with stage III and IV epithelial ovarian cancer (OC).
OC is a deadly gynaecological malignancy, with approximately 90% of cases classified as epithelial. According to GlobalData’s Ovarian Cancer: Opportunity Assessment and Forecast report, the number of diagnosed incident cases of OC in the seven major markets (7MM: France, Germany, Italy, Japan, Spain, the UK and the US) is expected to rise from 67,762 in 2025 to 71,308 by 2032.
In the FIRST/ENGOT-OV44 study, a total of 1,138 patients with advanced OC were randomised (1:1:2) to experimental arm 1 (PtCh + placebo and placebo maintenance; dropped from the study due to PARP inhibitor approval), arm 2 (PtCh + placebo and Zejula maintenance; n=385), and comparator arm 3 (PtCh + Jemperli and Jemperli/Zejula maintenance; n=753). The efficacy of arms 2 and 3 (intention-to-treat population) was evaluated based on the primary endpoint – investigator-assessed progression-free survival (PFS).
Statistically significant but clinically modest PFS benefit
The PFS showed a statistically significant difference between arm 3 and arm 2 (median 20.6 months versus 19.2; hazard ratio [HR] 0.85, 95% confidence interval [CI], 0.73–0.99, P = 0.0351), with a median duration follow-up of 53.1 months. The key secondary endpoint, overall survival (OS), had reached 57% maturity and was not statistically significant (median 44.4 versus 45.4 months; HR 1.01, 95% CI, 0.86–1.19, P = 0.9060). In the maintenance period, treatment-related adverse events above Grade 3 were reported in 41.1% of patients in arm 3 and 37.2% in arm 2. The study concludes that adding Jemperli to PtCh and Zejula provides a statistically significant but clinically modest PFS benefit, with no improvement in OS for newly diagnosed advanced OC patients.
The result was not unexpected, as immune checkpoint inhibitors have shown limited efficacy in OC, which is considered poorly immunogenic. At the end of 2024, Merck & Co’s Keytruda (pembrolizumab) and AstraZeneca’s Lynparza (olaparib) also failed to meet expectations in the KEYLYNK-001 study as a first-line therapy for OC, showing no OS benefit, similar to findings from the FIRST/ENGOT-OV44 study. Currently, no anti-PD-(L)1 therapies are approved for OC, and demonstrating a positive OS outcome is critical to gaining market share in this broad indication. A key difference between the two studies lies in patient selection. KEYLYNK-001 enrolled patients with breast cancer gene (BRCA) mutations, whereas the FIRST/ENGOT-OV44 trial included all-comers.
Jemperli’s global sales are projected to reach $2.56bn by 2030
To improve its chances of success, GSK made multiple modifications to the FIRST/ENGOT-OV44 trial design, including delaying readouts by several years. Initially, the primary endpoint was PFS in PD-L1-positive patients. In 2020, it was split into two groups, PFS in all-comers and PD-L1 expressers, before ultimately shifting the focus solely to all-comers. Another concern is the Jemperli and Zejula combination in the second-line setting for OC. A Phase III trial (NSGO-AVATAR) evaluating this combination was withdrawn due to a lack of financial support, suggesting GSK may not be optimistic about its prospects in the broader gynaecological cancer space.
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By GlobalDataAccording to GlobalData’s analyst consensus forecast, global sales for Jemperli and Zejula are projected to reach $2.56 billion and $1.26 billion, respectively, by 2030. In comparison, AstraZeneca’s Lynparza and blockbuster PD-1 blocker Merck’s Keytruda are expected to reach global sales of $2.4 billion and $22.71 billion, respectively. GSK acquired both Jemperli (co-developed with AnaptysBio) and Zejula through its $5.31 billion acquisition of Tesaro in 2019. After the FDA’s accelerated approval in 2021 for patients with mismatch repair-deficient endometrial cancer as a second-line treatment, Jemperli has become a cornerstone of GSK’s cancer portfolio alongside Zejula. In its most recent financial report, Jemperli sales increased 15% to $285 million in Q1 2025 due to broad-label expansion in first-line endometrial cancer regardless of biomarker status in the US. However, Jemperli holds a distinct advantage with its OS data over its main competitor, Keytruda, which also secured broad expansion in 2024. To expand Jemperli’s success beyond endometrial cancer, GSK will need to wait for positive Phase III results from other ongoing clinical trials: GALAXIES LUNG 301, AZUR-2, MITO 33, JADE, ROCSAN and COSTAR Lung.
