FDA decision for GSK drug opens door to treatment of more cancer patients


A GlaxoSmithKline drug for treating endometrial cancer with a certain genetic signature can now be used for solid tumors that have that same mutation regardless of where in the body the tumors are found. The expanded FDA approval for the GSK drug, Jemperli, positions the immunotherapy for a broader market but it still has a long way to go to catch up to Merck’s blockbuster drug, Keytruda.

The regulatory nod comes four months after Jemperli won its first approval, for endometrial cancer. As with that decision, the approved broader use of the drug is for those whose cancer has progressed despite prior treatment with chemotherapy.

The genetic alteration in question, mismatch repair deficiency (dMMR), affects a cell’s ability to repair the DNA mutations that lead to cancer. This mutation is common in colorectal cancer, as well as in the endometrial cancer indication for which Jemperli is already approved. According to the National Cancer Institute, dMMR mutations are also found in cancers of the breast, prostate, bladder, and thyroid. Jemperli is a type of immunotherapy called a checkpoint inhibitor. Like Keytruda, the GSK drug blocks PD-1, a “checkpoint” protein on immune cells that keeps them from attacking tumors. Blocking this protein enables immune cells to recognize and go after cancer cells.

The latest FDA approval for Jemperli was based on the results of an open-label Phase 1 study that evaluated 209 patients with recurrent or advanced solid tumors carrying the dMMR mutation. Patients were given a 500 mg dose of the intravenously infused drug once every three weeks for six weeks followed by a 1,000 mg dose once every six weeks until the cancer progressed or the drug’s toxicity became intolerable.

The study’s main goal was measuring overall response rate to treatment, assessed by the change in tumor size. The FDA said the GSK drug shrank tumors in 41.6% of patients. Of those responders, 9.1% had a complete response while 32.5% showed a partial response. The median duration of response was 34.7 months. For 95.4% of patients, response to treatment was six months or longer.

The most common adverse reactions reported in the clinical trial were fatigue, weakness, anemia, diarrhea, and nausea. Like other immunotherapies, including Keytruda, the drug’s label warns of immune-mediated adverse reactions that can be severe or even fatal.

Keytruda is approved for a long list of cancers, and it has become Merck’s top-selling product, accounting for $14.4 billion in 2020 revenue. In 2019, the FDA awarded Keytruda the first approval for treating cancer based on a particular genetic signature, regardless of where in the body tumors are found. Jemperli is one of three products in a thin GSK oncology portfolio. The drug generated £1 million in revenue in the second quarter of this year, according to GSK’s financial reports.

Use of Jemperli will require a test to confirm the dMMR mutation. Concurrent with the drug’s approval in solid tumors, the FDA also approved a Roche companion diagnostic to test for the genetic signature. The FDA’s decision to expand use of Jemperli is an accelerated approval, a speedier decision made with less data than the agency requires for a standard review. Retaining approval will require GSK to conduct additional studies to confirm that patients are benefiting from the therapy.

GSK added Jemperli to its pipeline via its $5.1 billion acquisition of Tesaro in 2019. Additional tests of Jemperli are ongoing that could potentially support expanding the use of the drug. GSK is testing the drug as an earlier line of treatment for endometrial cancer. The company is also evaluating the drug in combination with other therapies for potential applications in other types of cancer.

Photo by GlaxoSmithKline