GSK builds case for broader Jemperli label in endometrial cancer with Phase III data

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GSK

GSK builds case for broader Jemperli label in endometrial cancer with Phase III data

Published: Mar 18, 2024

By Tristan Manalac

BioSpace

GSK on Saturday unveiled new data from its Phase III RUBY program demonstrating better survival outcomes in a wide range of endometrial cancer patients treated with Jemperli (dostarlimab), potentially setting the PD-1 blocker up for a label expansion.

Hesham Abdullah, senior vice president and global head of oncology R&D at GSK, said in a statement that RUBY’s findings show that Jemperli-based regimens “could benefit a broader set of patients with endometrial cancer,” adding that the pharma has been amassing a “growing body of evidence supporting the role of dostarlimab-gxly as the backbone” of its immuno-oncology development program.

RUBY is a randomized and double-blinded Phase III study comprised of two parts. The first part assessed the efficacy and safety of Jemperli with carboplatin-paclitaxel, followed by maintenance with Jemperli monotherapy, versus carboplatin-paclitaxel with placebo and placebo maintenance therapy.

Part two used the same regimen of Jemperli with carboplatin-paclitaxel as an initial treatment, but combined the PD-1 inhibitor with GSK’s PARP inhibitor Zejula (niraparib) for maintenance treatment. The comparator arm received placebo with carboplatin-paclitaxel, followed by placebo.

Results from the first part showed that the Jemperli regimen significantly reduced the risk of death by 31% versus the chemotherapy counterpart. Patients in the Jemperli arm likewise had a “clinically meaningful improvement” in overall survival (OS) of 16.4 months.

The Jemperli combo was also similarly beneficial in an exploratory analysis of patients with mismatch repair proficient (MMRp)/microsatellite stable (MSS) tumors, cutting their risk of death by 21%. OS in this subpopulation improved by seven months.

GSK will file a regulatory submission in the first half of this year, using data from the first part of RUBY to expand Jemperli’s label to cover the overall endometrial cancer population, according to the pharma’s announcement.

Part two evaluated progression-free survival (PFS) and found that patients in the Jemperli-Zejula arm saw a 40% drop in the risk of disease progression or death. These patients also saw a clinically meaningful 6.2-month improvement in median PFS. In MMRp/MMS patients, the combo regimen reduced the risk of death or disease progression by 37% and increased median PFS by six months.

GSK previously announced positive PFS findings from part two of Ruby in December 2023, though it did not reveal specific data at the time.

Jemperli is a monoclonal antibody that works by targeting and binding the PD-1 receptor and blocking its interaction with corresponding ligands. This mechanism of action disables the cancer cells’ ability to evade the immune system and enhances the body’s anti-cancer immune activity.

The monoclonal antibody was first approved in 2021 for the treatment of recurrent or advanced endometrial cancer patients who are mismatch repair deficient. It has since picked up several more approvals, including one for frontline endometrial cancer in August 2023, beating out Merck’s dominant blockbuster treatment Keytruda (pembrolizumab).

Source: BioSpace