On August 1, 2024, the U.S. Food and Drug Administration (FDA) approved dostarlimab-gxly (Jemperli) with carboplatin and paclitaxel, followed by single-agent dostarlimab-gxly, for adult patients with primary advanced or recurrent endometrial cancer (EC). Dostarlimab-gxly previously was approved with carboplatin and paclitaxel, followed by single-agent dostarlimab-gxly, for primary advanced or recurrent EC that is mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H).
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Efficacy was evaluated in RUBY (NCT03981796), a randomized, multicenter, double-blind, placebo-controlled trial conducted in 494 patients with primary advanced or recurrent EC. Patients were randomized 1:1 to receive either dostarlimab-gxly with carboplatin and paclitaxel, followed by dostarlimab-gxly, or placebo with carboplatin and paclitaxel, followed by placebo. View the full prescribing information for details on the chemotherapy regimens. Randomization was stratified by MMR/ MSI status, prior external pelvic radiotherapy, and disease status (recurrent, primary stage III, or primary stage IV).
The major efficacy outcome measures were progression-free survival (PFS; as assess by the investigator using RECIST v1.1) in the dMMR/MSI-H and overall populations, and overall survival (OS) in the overall population. In the overall population, researchers observed a statistically significant median OS improvement of 44.6 months (95% CI = 32.6, not reached) and 28.2 months (95% CI = 22.1, 35.6) in the dostarlimab-gxly and placebo arms, respectively (HR = 0.69 [95% CI = 0.54, 0.89]; one-sided p = 0.002). Median PFS in the overall population was 11.8 months (95% CI = 9.6, 17.1) and 7.9 months (95% CI = 7.6, 9.5) in the dostarlimab-gxly and placebo arms, respectively (HR = 0.64 [95% CI = 0.51, 0.80]; one-sided p < 0.0001).
The most common adverse reactions reported in at least 20% of clinical trial participants who were treated with dostarlimab-gxly with carboplatin and paclitaxel were anemia, increased creatinine, peripheral neuropathy, decreased white blood cell count, fatigue, nausea, alopecia, low platelets, increased glucose, lymphopenia, neutropenia, liver function test abnormalities, arthralgia, rash, constipation, diarrhea, decreased albumin, abdominal pain, dyspnea, decreased appetite, increased amylase, urinary tract infection and vomiting. Immune-mediated adverse reactions with dostarlimab-gxly were similar to those previously reported for dostarlimab-gxly. See the full prescribing information for dostarlimab-gxly for a complete list of potential adverse reactions.
The recommended dostarlimab-gxly dose is 500 mg every three weeks for six cycles with carboplatin and paclitaxel, followed by 1,000 mg monotherapy every six weeks for up to three years or until patients experience disease progression or unacceptable toxicity. Administer dostarlimab-gxly before chemotherapy when both treatments are given on the same day.
The applicant used the Assessment Aid to facilitate FDA’s review. The agency approved the application three weeks ahead of FDA’s goal date. The agency also granted the application priority review. FDA’s expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions—Drugs and Biologics.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088.
For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.