GSK announced that the US Food and Drug Administration (FDA) has approved the use of Jemperli (dostarlimab) combined with carboplatin and paclitaxel (chemotherapy) and subsequently followed by Jemperli alone for treating adult patients with primary advanced or recurrent endometrial cancer.
This new approval expands the drug's previous indication to include patients with mismatch repair proficient (MMRp) or microsatellite stable (MSS) tumors, which constitute 70-75% of endometrial cancer cases and have limited treatment options.
The supplemental Biologics License Application (sBLA) supporting this expansion was granted Priority Review and approved ahead of the Prescription Drug User Fee Act deadline.
The approval is based on the results of the RUBY phase III trial, which demonstrated significant improvements in progression-free survival (PFS) and overall survival (OS). RUBY Part 1 is the only trial in this setting to show a statistically significant OS benefit in patients with primary advanced or recurrent endometrial cancer, with a 31% reduction in the risk of death compared to chemotherapy alone.
After 2.5 years, 61% of patients treated with Jemperli plus chemotherapy were alive, compared to 49% in the chemotherapy-only group. The median OS improved by 16.4 months with the combination treatment (44.6 months vs. 28.2 months). The median follow-up duration was over three years.
Safety and tolerability analyses indicated that the side effects of Jemperli combined with carboplatin-paclitaxel were consistent with the known profiles of these drugs.
Common side effects (≥ 20%) included nausea, alopecia, fatigue, peripheral neuropathy, anemia, arthralgia, constipation, diarrhea, myalgia, rash, hypomagnesemia, decreased appetite, peripheral sensory neuropathy, and vomiting.
The RUBY trial is a global, randomized, double-blind, multicenter phase III study involving patients with primary advanced or recurrent endometrial cancer. Part 1 compares dostarlimab plus carboplatin-paclitaxel followed by dostarlimab to carboplatin-paclitaxel plus placebo followed by placebo. Part 2 investigates dostarlimab plus carboplatin-paclitaxel followed by dostarlimab plus niraparib against placebo plus carboplatin-paclitaxel followed by placebo.
Part 1's primary endpoints were PFS and OS, assessed using the Response Evaluation Criteria in Solid Tumors v1.1. The statistical plan included pre-specified analyses of PFS and OS in both the mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) and overall populations. Part 1 included a broad patient population, including subtypes often excluded from trials, with 10% having carcinosarcoma and 20% with serous carcinoma.
Part 2's primary endpoint is PFS in the overall population, with PFS in the MMRp/MSS population and OS as key secondary endpoints. Secondary endpoints in both parts include PFS by blinded independent central review, PFS2, overall response rate, duration of response, disease control rate, patient-reported outcomes, and safety and tolerability.
Jemperli is a PD-1-blocking antibody and a key component of GSK's immuno-oncology research program. Ongoing trials are exploring its use alone and in combination with other therapies for various cancers, including gynecologic, colorectal, and lung cancers.
In the US, Jemperli is now approved in combination with carboplatin and paclitaxel, followed by Jemperli alone, for treating adult patients with primary advanced or recurrent endometrial cancer, including those with MMRp/MSS and dMMR/MSI-H tumors.
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