FDA approves dostarlimab-gxly with chemotherapy for endometrial cancer

2 Aug 2023
FDA approves dostarlimab-gxly with chemotherapy for endometrial cancer

The Food and Drug Administration approved dostarlimab-gxly with carboplatin and paclitaxel, followed by single-agent dostarlimab-gxly, for primary advanced or recurrent endometrial cancer (EC) that is mismatch repair deficient (dMMR), as determined by an FDA-approved test, or microsatellite instability-high (MSI-H).

Efficacy was evaluated in RUBY (NCT03981796), a randomised, multicenter, double-blind, placebo-controlled trial. Efficacy was assessed in a pre-specified subgroup of 122 patients with dMMR/MSI-H primary advanced or recurrent EC. MMR/MSI tumour status was determined by local testing assays (IHC, PCR, or NGS), or central testing (IHC), using the Ventana MMR RxDx Panel, when local results were unavailable.

Patients were randomised (1:1) to either dostarlimab-gxly with carboplatin and paclitaxel, followed by dostarlimab-gxly, or placebo with carboplatin and paclitaxel, followed by placebo. Chemotherapy regimens are described in the above link for full prescribing information. Randomisation was stratified by MMR/MSI status, prior external pelvic radiotherapy, and disease status (recurrent, primary Stage III, or primary Stage IV).

The primary efficacy outcome measure was investigator-assessed progression-free survival (PFS) using RECIST v 1.1. A statistically significant PFS improvement was observed in the dMMR/MSI-H population with a median PFS of 30.3 versus 7.7 months (Hazard Ratio=0.29 [95% CI: 0.17, 0.50]; p-value<0.0001), for the dostarlimab-gxly and placebo-containing regimens, respectively.

Immune-mediated adverse reactions occurred with dostarlimab-gxly, including pneumonitis, colitis, hepatitis, endocrinopathies, such as hypothyroidism, nephritis with renal dysfunction, and skin adverse reactions. The most common adverse reactions (≥20%) with dostarlimab-gxly in combination with carboplatin and paclitaxel were rash, diarrhoea, hypothyroidism, and hypertension. See the prescribing information for complete adverse reactions.

The recommended dostarlimab-gxly dose is 500 mg every 3 weeks for 6 doses with carboplatin and paclitaxel, followed by 1,000 mg monotherapy every 6 weeks until disease progression or unacceptable toxicity, or up to 3 years. Dostarlimab-gxly should be administered before chemotherapy when administered on the same day.

View full prescribing information for dostarlimab-gxly here.

Source: FDA