GSK, Merck in endometrial cancer face-off

GSK and Merck & Co have both reported new clinical data with the PD-1 checkpoint inhibitors, seeking an edge in the first-line treatment of advanced endometrial cancer.

Results of GSK’s RUBY trial of Jemperli (dostarlimab) and Merck’s NRG-GY018 study of Keytruda (pembrolizumab) were presented at the Society of Gynaecologic Oncology (SGO) annual meeting, with both showing improvements in progression-free survival (PFS).

The top-line readouts of the two trials have previously been released by both companies, but SGO is the first opportunity for oncologists to look at the full data, with initial reactions suggesting that Merck may have edged the contest.

In both studies, the PD-1 inhibitors plus chemotherapy were compared to chemo plus placebo and showed they were more effective at extending progression-free survival (PFS).

In RUBY, Jemperli reduced the risk of disease progression or death by 72% in patients with primary advanced or recurrent endometrial cancer patients whose tumours had mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) mutations, after two years’ follow-up.

In NRG-GY018, meanwhile, Keytruda achieved a 70% improvement in a dMMR population after one year’s follow up, with the two drugs therefore closely matched – mindful of the usual caveats about trying to compare trials with different protocols.

The potential separation of the two drugs lies in the other subgroup of patients with tumours that were mismatch repair proficient (pMMR), where Keytruda improved PFS by 46%.

For comparison, Jemperli reduced the risk of disease progression or death by 24% in RUBY, although GSK pointed out that its subpopulation also included patients' MSI-H mutations and overall enrolled a broader patient population that may be more reflective of what is seen in clinical practice.

That included patients with “histologies often excluded from clinical trials”, as well as approximately 10% of subjects with carcinosarcoma and 20% with serous carcinoma - particularly aggressive forms of endometrial cancer.

Both Keytruda and Jemperli already have approvals as monotherapies in second-line or later endometrial cancer settings, but approval in the first-line setting would unlock a larger eligible patient population.

GSK’s drug was cleared by the FDA for use in advanced endometrial cancer with dMMR mutations in 2021, and the company has said it plans to file Jemperli for first-line use in the first half of this year.

Keytruda, meanwhile, was greenlit by the FDA in patients with MSI-H or dMMR mutations last year, and is also approved in a combination regimen alongside Eisai’s Lenvima (lenvatinib) in previously-treated endometrial cancer without dMMR mutations.

GSK looks likely to have a lead over Merck in its filing schedule, but that window of opportunity could be short and, if oncologists are more convinced by the Keytruda data, could face a challenge carving out market share, given Keytruda’s well-established position in endometrial and other forms of cancer.

One area where GSK could carve out a niche relies on the second part of the RUBY trial, which is looking at Jemperli plus chemotherapy followed by Jemperli plus GSK’s PARP inhibitor Zejula (niraparib), versus chemo plus placebo followed by placebo.