GlaxoSmithKline plc Receives FDA Accelerated Approval for Jemperli (Dostarlimab-Gxly) for Adult Patients with Mismatch Repair-Deficient Recurrent or Advanced Solid Tumors
August 17, 2021 at 04:30 pm EDT
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GlaxoSmithKline 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 tumors, 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 tumor 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). Mismatch repair-deficient tumors contain abnormalities that affect the proper repair of DNA when copied in a cell. In the US, prevalence of dMMR across patients with solid tumors 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. Tumors with this biomarker are most commonly found in endometrial, colorectal and other gastrointestinal cancers, but may also be found in other solid tumors. 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-tumor (non-endometrial cancer) cohort F of the ongoing GARNET trial. The GARNET trial is a multicenter, non-randomized, 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 tumors, including endometrial and non-endometrial solid tumors (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 tumor 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 tumors who were evaluable for safety, the most commonly reported adverse reactions (=20%) were fatigue/asthenia (42%), anemia (30%), diarrhea (25%) and nausea (22%). The most common Grade 3 or 4 adverse reactions (=2%) were anemia, 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 JEMPERLI 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-tumor 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.
GSK plc is a global biopharma company. The Companyâs segments include Commercial Operations and Research and Development. It develops cancer medicines for patients, including ovarian cancer, endometrial cancer, and multiple myeloma. It has developed monoclonal antibodies to help treat different diseases. Its product areas include vaccines, specialty medicines, and general medicine. It is also focused on addressing the unmet treatment needs of patients with respiratory and inflammatory conditions. Its vaccine portfolio includes more than 20 vaccines that help to protect people from a range of diseases and infections, including meningitis, shingles and flu, among others. Its specialty medicines include medicines for immune-mediated conditions. Its specialty medicines are also engaged in developing medicines for respiratory disease and HIV. Its general medicines include inhaled medicines for asthma and chronic obstructive pulmonary disease, antibiotics, and medicines for skin diseases.
GlaxoSmithKline plc Receives FDA Accelerated Approval for Jemperli (Dostarlimab-Gxly) for Adult Patients with Mismatch Repair-Deficient Recurrent or Advanced Solid Tumors