FDA approves GSK endometrial cancer drug with specific genetic signature

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The FDA approved GlaxoSmithKline’s drug dostarlimab (Jemperli) for endometrial cancer. The immunotherapy drug, which carries a particular genetic signature, joins Merck's Keytruda as the checkpoint inhibitors approved for treating endometrial cancer, according to Frank Vinluan of Medcity News. GlaxoSmithKline acquired the drug as part of a $5 billion deal. It is the first approved such cancers carrying a particular genetic signature.

The decision for dostarlimab covers patients who have recurrent or advanced endometrial cancer that has progressed after an initial line of treatment with chemotherapy. The cancers need to have mismatch repair deficiency (dMMR), in which mutations affect the proper repair of DNA inside of a cell. This genetic feature, which is characteristic of several types of cancer, is found in some endometrial cancers. Prior to treatment, the dMMR signature has to be determined by a companion diagnostic. In another decision, the FDA approved a Roche Diagnostics test that identifies MMR deficiency.

Endometrial cancer affects the layer of cells lining the uterus. The most common cancer affecting female reproductive organs, endometrial cancer is expected be diagnosed 66,570 times this year, according to the American Cancer Society. Nearly 13,000 women are expected to die from it.

When endometrial cancer is diagnosed early, it can be treated with surgery. Jemperli offers another option for women whose cancer has advanced or has returned following chemotherapy. Such cases have less available treatments. The FDA said that between 25 and 30 percent of patients with advanced endometrial cancer have tumors carrying the dMMR signature.

Jemperli, a type of immunotherapy called a checkpoint inhibitor, is an antibody that blocks PD-1, a so-called checkpoint protein found on cancer cells. Cancers utilize this protein to avoid detection by the immune system. By blocking it, immune cells can target and kill cancer cells. Jemperli is the same type of drug as Merck’s pembrolizumab (Keytruda), a PD-1 inhibitor approved for treating numerous cancers. In 2020, Keytruda generated $14.4 billion in worldwide revenue.

In 2019 the FDA approved Keytruda in endometrial cancer for tumors not characterized by dMMR or mismatch instability high (MSI-H), a different mutation. It is approved for use in combination with Eisai drug lenvatinib (Lenvima).

The FDA’s Jemperli decision was based on the results of a single-arm clinical trial with 71 patients whose endometrial cancer was characterized by dMMR. Patients received a 500 mg dose of the intravenously infused drug once every three weeks for four doses, then a 1,000 mg dose once every six weeks until the cancer progressed or the toxicity of the drug became unacceptable.

In the study, 42.3 percent of patients had either a complete response (disappearance of the tumor) or a partial response (tumor shrinkage). For those responding to treatment, the response lasted six months or longer in 93 peercent of patients. Side effects included fatigue, nausea, diarrhea, anemia and constipation. The drug can also cause immune-mediated side effects, including inflammation of healthy organs.

Jemperli could also be approved to treat other kinds of cancer. GSK is continuing Phase 1 tests in patients with other types of advanced solid tumors.