GSK receives FDA accelerated approval for JEMPERLI (dostarlimab-gxly) for adult patients with mismatch repair-deficient (dMMR) recurrent or advanced solid tumours

GlaxoSmithKline (GSK) plc announced the US Food and Drug Administration (FDA) approved a new indication for JEMPERLI (dostarlimab-gxly), a programmed cell death receptor-1 (PD-1) blocking antibody, for the treatment of adult patients with mismatch repair-deficient (dMMR) recurrent or advanced solid tumours, as determined by an FDA-approved test, that have progressed on or following prior treatment and who have no satisfactory alternative treatment options. This indication received accelerated approval based on tumour response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

Dr Hal Barron, Chief Scientific Officer and President R&D, GSK, said: “For patients with tumours expressing the dMMR biomarker, there continues to be a significant need for new and effective treatments. I’m excited about GSK’s second oncology FDA approval this year, and the new treatment option it provides for these patients.”

Mismatch repair-deficient tumours contain abnormalities that affect the proper repair of DNA when copied in a cell. In the US, prevalence of dMMR across patients with solid tumours has been estimated at 14%. Mismatch repair-deficient status is a biomarker that has been shown to predict response to immune checkpoint blockade with PD-1 therapy. Tumours with this biomarker are most commonly found in endometrial, colorectal and other gastrointestinal cancers, but may also be found in other solid tumours.

Dr Jubilee Brown, Professor and Division Director of Gynecologic Oncology at Atrium Health Levine Cancer Institute, and investigator on the GARNET study, said: “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. 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.”

This new indication follows an FDA priority review of the Biologics License Application and is based on the collective results from the dMMR endometrial cancer cohort A1 and the dMMR solid-tumour (non-endometrial cancer) cohort F of the ongoing GARNET trial. The GARNET trial is a multicentre, non-randomised, multiple parallel-cohort, open-label study. Cohort F included patients with dMMR recurrent or advanced non-endometrial cancers, with the highest prevalence in colorectal, small intestine and stomach cancers.

The major efficacy outcomes of the GARNET trial are objective response rate (ORR) and duration of response (DoR), as assessed against RECIST v 1.1 by blinded independent central review. Results in all dMMR solid tumours, including endometrial and non-endometrial solid tumours (n=209), demonstrated an ORR of 41.6% (95% CI; 34.9-48.6) with a complete response rate of 9.1% and a partial response rate of 32.5%. The median DoR was 34.7 months (range 2.6-35.8+) with 95.4% of patients maintaining a response for six months or longer. In the dMMR solid tumour non-endometrial cancer cohort (n=106), results demonstrated an ORR of 38.7% (95% CI; 29.4-48.6).

Patients received 500 mg of dostarlimab as an intravenous infusion once every three weeks for four doses, followed by 1,000 mg once every six weeks until disease progression or unacceptable toxicity. Among the 267 patients with recurrent or advanced dMMR solid tumours who were evaluable for safety, the most commonly reported adverse reactions (≥20%) were fatigue/asthenia (42%), anaemia (30%), diarrhoea (25%) and nausea (22%). The most common Grade 3 or 4 adverse reactions (≥2%) were anaemia, fatigue/asthenia, increased transaminases, sepsis and acute kidney injury. Grade 3 or 4 laboratory abnormalities (≥2%) included decreased lymphocytes, decreased sodium, increased alkaline phosphatase and decreased albumin.

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

With the dMMR solid-tumour approval, the US prescribing information for this indication includes efficacy data for an additional 32 patients in the endometrial cancer cohort A1 (n=103). The additional results for this cohort show an ORR of 44.7% (95% CI; 34.9-54.8) with a DoR range of 2.6-35.8+ months. The results of the endometrial cancer cohort of the GARNET trial represent the largest dataset to date evaluating an anti-PD-1 as monotherapy treatment for women with endometrial cancer.

As we work to expand our oncology pipeline and portfolio of cancer treatments, GSK is also studying dostarlimab in earlier lines of treatment for endometrial cancer and in combination with other therapeutic agents for patients with advanced/metastatic cancers beyond endometrial cancer.