GSK claims a first with Jemperli in endometrial cancer

GSK has built the case for first-line use of its PD-1 inhibitor Jemperli in endometrial cancer, with new survival data that could help it expand the label for the drug.

The latest readout from the RUBY trial shows that adding Jemperli (dostarlimab) to standard chemotherapy with carboplatin and paclitaxel improved overall survival (OS) compared to chemotherapy plus placebo, reinforcing earlier results showing that it extended the time to disease progression or death.

The trial compared Jemperli to placebo given on top of chemo, then follow-up treatment with Jemperli or placebo, in adult patients with primary advanced or recurrent endometrial cancer.

According to GSK, a “clinically meaningful” improvement in OS was seen in patients with mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) mutations – for which Jemperli is already approved – as well as a mismatch repair proficient (MMRp)/microsatellite stable (MSS) subgroup.

According to the company’s global head of oncology R&D, Hesham Abdullah, RUBY is the first immunotherapy combination study to show a survival benefit in this setting.

“We look forward to sharing detailed results of this analysis with regulatory authorities and the larger scientific community,” he said.

Jemperli was approved for front-line use in endometrial cancer in the summer on the strength of a 74% improvement in progression-free survival (PFS) in RUBY, but the FDA limited the drug to the sMMR and MSI-H population, saying that most of the benefit came from that group. Approval in Europe for dMMR/MSI-H endometrial cancer is expected in the first half of next year.

Now, all eyes will be on the size of the OS benefit across both patient groups to see if it might persuade the regulator to extend the label for the drug to include an all-comer population – which GSK has said could help it grow Jemperli’s sales above the $1 billion threshold. So far, sales are modest, at £36 million (about $44 million) in the first half of this year.

Competition could come quite quickly, however, including from MSD’s Keytruda (pembrolizumab), which in the NRG-GY018 trial was also shown to extend PFS in dMMR/MSI-H patients when used first-line for advanced endometrial cancer. That study was not designed to track OS, however, and was unblinded after the PFS endpoint was reached.

Both Keytruda and Jemperli already have approvals as monotherapies in second-line or later endometrial cancer settings, so, Jemperli's first-line approval already gives it an edge in the market, which could widen if its label is expanded.

By GSK’s reckoning, there are around 60,000 new cases of endometrial cancer diagnosed each year in the US, with 15% to 20% of them at the advanced or metastatic stage. Of these, 20% to 29% are dMMR or MSI-H.

Also angling for a piece of the market is AstraZeneca, which recently reported encouraging PFS results from the DUO-E trial of its PD-L1 inhibitor Imfinzi (durvalumab) alongside chemo – with or without its PARP inhibitor Lynparza (olaparib) – in previously-untreated endometrial cancer.

The RUBY trial is also looking at triplet therapy with Jemperli, chemo, and GSK’s PARP inhibitor Zejula (niraparib), with results from that arm due next year.