FDA approves Jemperli for advanced endometrial cancer

The US Food and Drug Administration (FDA) has granted GlaxoSmithKline’s Jemperli (dostarlimab) accelerated approval for treating patients with recurrent or advanced endometrial cancer that has progressed on or following prior treatment with a platinum-containing chemotherapy and whose cancers have a specific genetic feature known as deficient mismatch repair (dMMR, which affects the repair of DNA inside the cell), as determined by an FDA-approved test.

“Today’s approval of Jemperli is evidence of the FDA’s progress in applying precision medicine to expand treatment options for patients with cancer,” stated Dr Richard Pazdur, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research. “This immunotherapy was specifically studied to target dMMR endometrial cancer and leverages scientific knowledge surrounding the mechanism of immunotherapy response in this unmet medical need population.”

Endometrial cancer is the most common gynaecologic malignancy in the US and though three quarters of cases are diagnosed at an early stage when it can be cured with surgery, for women with advanced and recurrent endometrial cancer there are limited therapeutic options following front-line standard treatment with a platinum-containing chemotherapeutic regimen. It is estimated that up to 30 percent of patients with advanced endometrial cancer have dMMR tumours.

Jemperli targets the cellular pathway known as PD-1/PD-L1. PD-1 is expressed on the body’s T cells and has an immunosuppressive function, which is hijacked by cancer to prevent the immune system from clearing the tumour. By inhibiting this pathway, Jemperli assists the immune system in fighting cancer.

The accelerated approval was granted after Jempeli was shown to be safe and effective in a single-arm, multi-cohort clinical trial. In the trial, 71 patients with dMMR recurrent or advanced endometrial cancer received Jemperli. Overall, 42.3 percent had a complete or a partial response to treatment with Jemperli that lasted six months or more in 93 percent of responders.

The most common side effects with Jemperli were fatigue, nausea, diarrhoea, anaemia and constipation. The treatment can also cause immune-mediated side effects, including inflammation of healthy organs such as the lungs (pneumonitis), colon (colitis), liver (hepatitis), endocrine glands (endocrinopathies) and kidneys (nephritis).

Patients who experience severe or life-threatening infusion-related reactions should stop taking Jemperli. Women who are pregnant or breastfeeding should not take Jemperli because it may cause harm to a developing foetus or newborn baby. The safety and effectiveness of Jemperli in pediatric patients are not known.

The accelerated approval pathway, under which Jemperli was approved, allows the FDA to approve drugs for serious conditions where there is unmet medical need and a drug is shown to have certain effects that are reasonably likely to predict a clinical benefit to patients. Despite the approval, further trials will be required to verify and describe anticipated clinical benefits of Jemperli. These are currently being conducted by the sponsor in additional patients with dMMR endometrial tumours.