GSK is crowing about a victory for its PD-1 inhibitor Jemperli after it was quickly approved by the FDA for use in a subset of patients with endometrial cancer.
Individuals with primary progressed or first recurrent endometrial cancer who took Jemperli in combination with chemotherapy lived significantly longer, GSK reported on Monday.
Hesham Abdullah, M.D., who serves as GSK’s head of oncology clinical development, mentioned that Jemperli’s enhancement of overall survival was both statistically significant and held clinical significance. He emphasized that this development represents a milestone as it’s the first instance where a PD-1/L1 inhibitor has shown a benefit in overall survival for first-line endometrial cancer.
One key goal of the RUBY study is overall survival. An earlier interim study shown that Jemperli in conjunction with chemotherapy significantly reduced the risk of tumor growth or mortality compared to chemotherapy alone. There was a tendency toward improved overall survival of 36% with the GSK combination, although this increase was not statistically significant at the time.
Finally, in July, GSK received FDA clearance for Jemperli in combination with chemotherapy for a subset of patients with endometrial cancer whose tumors are characterized by mismatch repair deficiency (dMMR) or microsatellite instability (MSI-H).
GSK said that it chose an indication where Jemperli showed the most promising therapeutic outcome in order to submit the application quickly.
When asked about Jemperli’s advantage in the dMMR/MSI-H and pMMR/microsatellite-stable categories, Abdullah stated they were clinically meaningful now that the study’s OS endpoint had been accomplished in the total trial cohort.
GSK’s efforts to expand Jemperli’s authorization for first-line endometrial cancer treatment will hinge on the exact OS findings in the pMMR cohort. Jemperli demonstrated a preliminary 27% decrease in mortality risk in pMMR patients during the last interim study.
Abdullah did not elaborate on how the new OS data may be characterized, but he did say that GSK is “extremely excited.” According to him, the British pharmaceutical company intends to present the whole findings at a forthcoming medical conference and to the FDA.
The Jemperli-chemotherapy regimen is just one of the several experimental modalities in RUBY. The results of the trial, which examine whether or not the PARP inhibitor Zejula should be added to Jemperli for the maintenance period of treatment, are due in the first half of 2024, according to Abdullah.
Other PD-1/L1 developers may challenge GSK’s chemo/PARP combination and PARP triplet treatment plans.
Merck’s PD-1 king Keytruda scored a comparable success along with chemotherapy in first-line endometrial cancer in the third phase of the NRG-GY018 study, around the same time as GSK’s earlier progression-free survival readout. Although the follow-up duration was substantially shorter for the pMMR group, cross-trial comparison suggested that Keytruda performed better than Jemperli.
At the recent annual conference of the European Society for Medical Oncology, AstraZeneca presented comprehensive data on the use of its PD-L1 inhibitor Imfinzi in combination with chemotherapy and the PARP inhibitor Lynparza for the treatment of advanced endometrial cancer in patients at high risk of the disease. The pMMR population in the DUO-E study seemed to profit the most from the addition of Lynparza, whereas the dMMR group did not seem to gain anything from the PARP medication.