The European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has adopted a positive opinion in favor of the approval of dostarlimab (Jemperli) and chemotherapy for adults diagnosed with mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H), primary advanced or recurrent endometrial cancer who are eligible for systemic therapy, according to a press release from GSK.1
The CHMP’s opinion is one of the final steps before the European Commission can authorize use of the combination regimen.
Supporting data for the positive opinion came from the first part of the phase 3 RUBY/ENGOT-EN6/GOG3031/NSGO trial(NCT03981796), which were presented at the European Society for Medical Oncology (ESMO) Virtual Plenary and the Society of Gynecologic Oncology (SGO) Annual Meeting.
Part 1 of the RUBY trial met its primary endpoint of progression-free survival (PFS) in patients treated with dostarlimab plus carboplatin and paclitaxel in the dMMR/MSI-H population. Investigators observed a 72% reduction in the risk of disease progression or death compared with placebo plus chemotherapy (HR, 0.28; 95% CI, 0.16-0.50).2 Additionally, there was a 70% reduction in the risk of death with the combination regimen compared with chemotherapy alone in the dMMR/MSI-H population, according to a prespecified exploratory analysis (HR, 0.30; 95% CI, 0.13-0.70).
“We are pleased with this positive CHMP opinion and the potential for dostarlimab with chemotherapy to treat patients with this very challenging form of endometrial cancer,” Hesham Abdullah, senior vice president and Global Head Oncology, R&D at GSK, said in the press release. “If approved, dostarlimab plus chemotherapy will be the first new treatment option in decades for these patients in the European Union, offering long-awaited new hope for improved long-term outcomes. This opinion further reinforces our confidence in dostarlimab’s important role in the immuno-oncology treatment landscape.”
In the two-part global, randomized, double-blind, multicenter trial, 494 patients with primary advanced or recurrent endometrial cancer were randomly assigned either dostarlimab or a placebo. The study’s dual-primary endpoints were PFS and OS.
Frequent adverse effects (AEs) associated with dostarlimab plus carboplatin and paclitaxel include rash, hypothyroidism, increased alanine aminotransferase and aspartate aminotransferase, pyrexia, and dry skin. Frequent AEs specific to dostarlimab include anemia, nausea, diarrhea, vomiting, joint pain, itching, rash, fever, and hypothyroidism.Investigators have reported several immune system AEs, as well, such as inflammation, rash, and infusion reactions.3
Currently, dostarlimab has conditional approval as a monotherapy for treating adult patients with dMMR/MSI-H, recurrent or advanced endometrial cancer that has progressed. If the European Commission approves dostarlimab plus chemotherapy, it is expected that the conditional approval will convert to a full approval.
Dostarlimab/chemotherapy was approved by the FDA for dMMR/MSI-H, primary advanced or recurrent endometrial cancer in July 2023 based on findings from the RUBY trial.4