FDA approves dostarlimab-gxly with chemotherapy for endometrial cancer
Regulatory approval: On July 31, 2023, the FDA approved dostarlimab-gxly (Jemperli) with carboplatin and paclitaxel, followed by single-agent dostarlimab-gxly, for primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR) as determined by an FDA-approved test, or microsatellite instability–high (MSI-H). The approval was supported by the RUBY trial subgroup (n=122 dMMR/MSI-H), where investigator-assessed PFS improved versus placebo-containing regimens (median 30.3 vs 7.7 months; HR 0.29).
FDA approval (July 31, 2023)
The US Food and Drug Administration (FDA) approved dostarlimab-gxly (Jemperli; GlaxoSmithKline) in combination with carboplatin and paclitaxel, followed by single-agent dostarlimab-gxly, for primary advanced or recurrent endometrial cancer that is dMMR (by an FDA-approved test) or MSI-H.
Key efficacy evidence
Efficacy was evaluated in RUBY (NCT03981796), a randomized, multicenter, double-blind, placebo-controlled trial. The FDA reported results for a pre-specified subgroup of 122 patients with dMMR/MSI-H primary advanced or recurrent endometrial cancer. MMR/MSI status was determined via local assays (IHC, PCR, or NGS) or central IHC (Ventana MMR RxDx Panel) when local results were unavailable.
Patients were randomized 1:1 to dostarlimab-gxly plus carboplatin/paclitaxel followed by dostarlimab-gxly, or placebo plus chemotherapy followed by placebo. The primary endpoint was investigator-assessed PFS (RECIST v1.1). Median PFS was 30.3 vs 7.7 months (HR 0.29, 95% CI 0.17–0.50; p<0.0001) for dostarlimab-gxly–containing vs placebo-containing regimens, respectively.
Safety and dosing (per FDA communication)
Immune-mediated adverse reactions were reported (eg, pneumonitis, colitis, hepatitis, endocrinopathies, nephritis/renal dysfunction, skin reactions). Common adverse reactions (≥20%) with the combination included rash, diarrhea, hypothyroidism, and hypertension. Recommended dosing: 500 mg every 3 weeks for 6 doses with chemotherapy, then 1,000 mg every 6 weeks until progression/unacceptable toxicity, or up to 3 years; administer dostarlimab-gxly before chemotherapy on the same day.
Regulatory context
The review occurred under Project Orbis with ongoing reviews at collaborating agencies outside the FDA.