GSK Wins Big as FDA Expands Checkpoint Inhibitor's Reach

GSK_Cristina Arias/Cover/Getty Images

Cristina Arias/Cover/Getty Images

In April, the U.S. Food and Drug Administration (FDA) approved GlaxoSmithKline’s PD-1 checkpoint inhibitor Jemperli (dostarlimab) for adults with mismatch repair-deficient (dMMR) recurrent or advanced endometrial cancer.

Today, the U.K.-based company announced that the agency had approved the drug for a wider group of indications for adults with dMMR recurrent or advanced solid tumors. The tumors’ status is evaluated with an FDA-approved assay.

Specifically, the new approval was for adults with dMMR recurrent or advanced solid tumors who have progressed on or after previous treatment and who have no satisfactory alternatives. The expanded label was based on tumor response rate and durability of response and via an Accelerated Approval pathway. Continuing the approval will be based on verification and proof of clinical benefit in confirmatory studies.

In normal cells, mismatch repair (MMR) fixes errors created during DNA replication. Typically, the enzymes that are part of the MMR system fix the DNA by identifying and correcting the abnormal strands. When the repair mechanism isn’t working properly, it is known as mismatch repair-deficient, where the enzymes don’t work the way they’re supposed to. In the U.S., dMMR in solid tumors is believed to occur in about 14% of patients. dMMR status has been demonstrated to predict checkpoint inhibitor response. They are most common in endometrial, colorectal and other gastrointestinal tumors, and also in other solid tumors.

Jemperli is an anti-PD-1 antibody that binds to the PD-1 receptor and blocks its interaction with the PD-1 ligands PD-L1 and PD-L2. The drug was discovered by AnaptysBio and licensed to Tesaro in March 2014. GSK completed its acquisition of Tesaro in January 2019.

“For patients with tumors expressing the dMMR biomarker, there continues to be a significant need for new and effective treatments,” said Dr. Hal Barron, chief scientific officer and president of research and development for GSK. “I’m excited about GSK’s second oncology FDA approval this year, and the new treatment option it provides for these patients.”

The new approval was based on a priority review of the company’s Biologics License Application (BLA) and the accumulated results from the dMMR endometrial cancer cohort A1 and the dMMR solid-tumor (non-endometrial cancer) cohort F of the ongoing GARNET study. Cohort F includes patients with dMMR recurrent or advanced non-endometrial cancers.

The GARNET trial’s primary efficacy outcomes are objective response rate (ORR) and duration of response (DoR). In all dMMR solid tumors, the ORR was 41.6% and the complete response was 9.1%, with a partial response rate of 32.5%. Median DoR was 34.7 months, with 95.4% of patients maintaining the response for at least six months.

GSK is also evaluating Jemperli in earlier lines of treatment for endometrial cancer and combination with other drugs for advanced or metastatic cancers other than endometrial cancer.

“Jemperli 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 Dr. Jubilee Brown, professor and division director of Gynecologic Oncology at Atrium Health Levine Cancer Institute and investigator on the GARNET study. “As we saw in the GARNET trial, of those patients who respond to treatment with Jemperli, nearly all continued to respond for six months or longer.”

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