On a mission to grow in oncology, GSK has more positive data to report in endometrial cancer. This time, the company is touting results for its PD-1 inhibitor Jemperli and PARP inhibitor Zejula, which could become a threat to a rival therapy at AstraZeneca.
Adding Jemperli and Zejula to chemotherapy significantly extended the time before tumor progression or death in patients with primary advanced or recurrent endometrial cancer that’s mismatch repair proficient or microsatellite stable (pMMR/MSS), GSK said Monday.
The results came from the second part of the phase 3 RUBY trial. The trial also showed that the Jemperli-Zejula-chemo regimen was better at delaying disease worsening than chemo alone in the overall population, regardless of genetic stability. But GSK appears to think that the combo has more value in the pMMR/MSS subgroup.
Patients with pMMR/MSS endometrial cancer have few treatment options, Hesham Abdullah, GSK’s head of oncology R&D, said in a statement.
“Today’s positive topline results reinforce our approach of building combination therapies with [Jemperli] as the backbone in an effort to improve patient outcomes and options,” Abdullah said.
Before Monday’s announcement, GSK in July won FDA approval for Jemperli and chemo—without Zejula—to treat endometrial cancer that’s mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H). The first part of the RUBY trial showed that Jemperli and chemo cut the risk of progression or death by 72% compared with chemo alone in dMMR/MSI-H endometrial cancer.
In part 1 of RUBY, patients received Jemperli and chemo, followed by Jemperli alone. In part 2, Zejula was added to Jemperli only during the maintenance phase.
That massive progression-free survival benefit in part 1 of the study reflects the power of PD-1/L1 inhibitors such as Jemperli in various kinds of dMMR/MSI-H tumors. It also leaves little room for GSK to further improve outcomes in this patient population by adding Zejula to the mix.
In October, meanwhile, AstraZeneca provided detailed results from its phase 3 DUO-E trial. It showed that adding AZ’s PD-L1 inhibitor on top of chemo cut the risk of progression or death by 58% in dMMR/MSI-H endometrial cancer.
The magnitude of improvement was almost identical, at 59%, for a combo that also includes AZ and Merck’s PARP inhibitor Lynparza.
By comparison, in the pMMR subgroup, the addition of Lynparza widened the 23% progression-free survival benefit from the Imfinzi-chemo combo to 43%.
Results from the current RUBY part 2 analysis will be shared with regulatory authorities, GSK said. Data on whether the Zejula combo extended patients’ lives remained immature, and investigators are still following patients for that data, according to the company.
In October, GSK said part 1 of RUBY hit its overall survival goal as the Jemperli-chemo combo demonstrated statistically significant and clinically meaningful improvement over chemo alone in the overall population.
Overall survival data are important for a PARP-containing regimen. The FDA recently noticed potential harm from PARP regimens in certain ovarian cancer patients over the long term. Because of the FDA’s classwide scrutiny, GSK about a year ago withdrew Zejula’s use as a maintenance therapy in some ovarian cancer patients who’ve responded to second-line chemotherapy. That indication now only covers patients with germline BRCA mutations.