FDA Grants Accelerated Approval to Dostarlimab-gxly for dMMR Recurrent/Advanced Solid Tumors

The regulatory decision is based on findings from collective data from the dMMR endometrial cancer cohort A1 and the dMMR solid-tumor, non-endometrial cancer, cohort F of the ongoing phase 1 GARNET trial (NCT02715284).

The FDA granted accelerated approval to dostarimab-gxly (Jemperli) for the treatment of adults with mismatch repair-deficient (dMMR) recurrent or advanced solid tumors, so long as the patient has progressed beyond previous treatment and has no satisfactory alternative treatment options, according to GSK.

“Dostarlimab is an important new treatment option for patients with mismatch repair-deficient recurrent or advanced solid cancers who have progressed and have no alternative options,” said Jubilee Brown, MD,professor of gynecologic oncology, Levine Cancer Institute, and GARNET study investigator, in a press release. “As we saw in the GARNET trial, of those patients who respond to treatment with dostarlimab, nearly all continued to respond for six months or longer.”

The regulatory decision is based on findings from collective data from the dMMR endometrial cancer cohort A1 and the dMMR solid-tumor, non-endometrial cancer, cohort F of the ongoing phase 1 GARNET trial (NCT02715284), the results of which represent the largest dataset to assess anti-PD-1 as a monotherapy treatment in women with endometrial cancer.

The data showed that objective respone rate (ORR) was 41.6% (95% CI, 34.9-48.6) among the 209 patients with dMMR solid tumors, including endometrial and non-endometrial solid tumors. In addition, the data reported a partial response rate of 32.5% and a mediation duration of response (DOR) of 34.7 months. The DOR ranged between 2.6 months and 25.8 months, however, 95.4% of patients experienced a response that lasted for 6 months or more. The ORR among the 106 patients with dMMR solid tumor non-endometrial cancer treated with dostarlimab was 38.7% (95% CI, 29.4-48.6).

Patients were administered 500 mg of dostarlimab once every 3 weeks for 4 cycles, and then 1,00 mg once every 6 weeks until either the disease progressed or the toxicity was unacceptable.

The most commonly reported adverse events (AE) were fatigue or asthenia (42%), anaemia (30%), diarrhea (25%), and nausea (22%). The most common AEs reported at grade 3 or 4 included anaemia, fatigue, asthenia, increased transaminases, sepsis, and acute kidney injury. Researchers also noted grade 3 and 4 laboratory abnormalities, such as increased alkaline phosphatase, decreased sodium, decreased lymphocytes, and decreased albumin.

In April 2021, the FDA garnted dostarlimab an accelerated approval for the treatment of adult patients with dMMR recurrent or advanced endometrial cancer, as determined by an FDA-approved test, that has progressed on or following prior treatment with a platinum-containing regimen. That approval was based on findings from cohort A1, which included 71 patients with dMMR endometrial cancer.

Dostarlimab is also currently being evaluated as an earlier line treatment and in combination with other therapies to treat cancers besides endometrial.

Reference

GSK receives FDA accelerated approval for JEMPERLI (dostarlimab-gxly) for adult patients with mismatch repair-deficient (dMMR) recurrent or advanced solid tumours. News release. GSK. August 17, 2021. Accessed August 17, 2021. https://www.gsk.com/en-gb/media/press-releases/gsk-receives-fda-accelerated-approval-for-jemperli-dostarlimab-gxly-for-adult-patients-with-mismatch-repair-deficient-dmmr-recurrent-or-advanced-solid-tumours/