FDA approves dostarlimab for the treatment of recurrent or advanced endometrial cancer_Cornhule

Endometrial cancer originates from malignant tumors of the endometrial glands, also known as uterine corpus cancer, and the vast majority are adenocarcinomas. It is one of the three major malignant tumors of the female genitalia. In our country, with the development of society and the improvement of economic conditions, the incidence of endometrial cancer has increased year by year. It currently ranks second only to cervical cancer and ranks second among malignant tumors of the female reproductive system. What we bring to you today is dostarlimab, a drug for the treatment of recurrent or advanced mismatch repair-deficient endometrial cancer, which has been approved and relevant clinical trials are ongoing.

Study details

The U.S. Food and Drug Administration (FDA) has fast-tracked approval of dostarlimab gxly (Jemperli) is indicated for the treatment of adult patients with recurrent or advanced endometrial cancer whose disease has progressed on or after prior platinum-containing chemotherapy and whose disease has a specific genetic signature of mismatch repair deficiency (dMMR) as determined by an FDA-approved test. If clinicians can use dostarlimab, it will solve the problem of limited first-line treatment options for 25% to 30% of patients with advanced endometrial cancer.

Trial results: Based on the results of a single-arm, multi-cohort clinical trial of 71 patients with dMMR recurrent or advanced endometrial cancer, the FDA approved dostarlimab for the treatment of this indication. In this trial, 42.3% of patients receiving dostarlimab achieved complete responses (CRs) or partial responses (PRs). Notably, 93% of responders had responses that lasted at least 6 months.

Common toxicities observed in patients receiving dostarlimab include fatigue, nausea, diarrhea, anemia, and constipation. Immune-mediated adverse events associated with dostarlimab include pneumonia, colitis, hepatitis, endocrine disorders, and nephritis. Dostarlimab targets and blocks the PD-1/PD-L1 pathway and assists the body's immune system in fighting cancer cells. The drug's ability to activate responses in patients with dMMR disease was also demonstrated in the endometrial cancer cohort of the Phase 1 GARNET trial (NCT02715284), which included 126 patients with dMMR endometrial cancer.

A subgroup analysis of dMMR endometrial cancer patients showed that the objective response rate was 44.7%, including 11 cases of CR and PR. 35 cases, 39 cases were in stable condition. The median duration of response (DOR) was not reached in this cohort (range 2.63-28.09+).

Safety: Preliminary analysis of the GARNET trial demonstrates the safety of this agent. In the dMMR cohort, 95.2% of patients experienced treatment-emergent adverse events (TEAEs) of any grade. The incidence rate of grade 3 or above adverse reactions in dMMR endometrial cancer was 48.4%. More than 63% of toxicities observed in this cohort were considered to be related to the trial drug, and 9.5% of patients had severe toxicities.

Immune-related adverse reactions of any grade also occurred in the trial, the most common being hypothyroidism (5.6%), diarrhea (4.8%), and increased aspartate aminotransferase (1.6%). The incidence of grade 3 or higher immune-related adverse events of elevated alanine aminotransferase (ALT) was 1.6%, and the incidence of diarrhea was also 1.6%. The incidence of grade ≥3 amylase elevations was observed in 0.8% of this cohort.

GARNET is evaluating dostarlimab in patients with advanced solid tumors. The total number of patients in the trial is 740. In the dMMR endometrial cancer cohort, patients received dostarlimab at doses of 160 mg, 20 mg/mL, 500 mg, or 50 mg/mL. The primary endpoints of the trial include ORR and DOR. The trial is also exploring multiple safety endpoints.

Reference: https://www.targetedonc.com/view/fda-approves-dostarlimab-for-recurrent-or-advanced-dmmr-endometrial-cancer