FDA Approval of Jemperli Plus Chemo ‘Changed the Game’ for Endometrial Cancer

The recent approval by the Food and Drug Administration (FDA) of Jemperli (dostarlimab) plus chemotherapyfollowed by standalone Jemperli for the treatment of adults with primary advanced or recurrent mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H) endometrial cancer is a landmark moment for patients, as one expert told CURE®.

“What this new FDA approval has done (is) expand options, while providing patients some possibilities for actual cure, even in the settings of recurrence or advanced-stage disease.This is something that we previously really didn't have to offer,” said Dr. Eloise Chapman-Davis, who specializes in gynecologic oncology at Weill Cornell Medicine in New York City and is a member of the Foundation for Women’s Cancer’s board of directors.

The FDA approved Jemperli plus carboplatin and paclitaxel followed by Jemperli, according to a July 31 news release from Jemperli manufacturer GSK, making it the first frontline immunotherapy and chemotherapy combination to be approved for this population of patients with endometrial cancer.

Mismatch repair deficiency describes cells with many DNA mutations which could potentially result in cancer, while microsatellite instability refers to cancer cells with a high number of mutations within microsatellites, short sequences of DNA.

The recent approval arrives in the wake of interim analysis results of part 1 of the RUBY/ENGOT-EN6/GOG3031/NSGO phase 3 trial, findings of which were published in June in The New England Journal of Medicine. Researchers found that patients with dMMR-MSI-H endometrial cancer treated with Jemperli displayed a 61.4% 24-month progression-free survival rate (how long a patient lives without the disease worsening), compared to 15.7% among patients treated with placebo plus carboplatin and paclitaxel.

In the total participant population, the 24-month progression-free survival rate was 36.1% for those treated with Jemperli versus 18.1% for those treated with placebo, although the overall survival (when a patient lives following treatment, regardless of disease status) rates at 24 months were 71.3% and 56%, respectively.

With more than 700 participants, the two-part trial launched in 2019 and is estimated to be completed in November 2026, according to its listing on clinicaltrials.gov. GSK noted in its release that the trial “included a broad (patient) population, including histologies often excluded from clinical trials and had approximately 10% of patients with carcinosarcoma and 20% with serous carcinoma.”

“What was really phenomenal about this large, randomized control trial that looked at patients with both advanced stage and recurrent endometrial cancer, is that it included all of the histology subtypes,” said Chapman-Davis. “Many previous studies were more likely to excludemore aggressive subtypes, specifically carcinosarcoma, while this study was one of the only trials using (Jemperli) and chemotherapy (paclitaxel and carboplatin), to include this previously left-out subgroup of patients harboring this histology subtype.

“And not only did they include all comers, they also showed that there was benefit for both progression-free survival and overall survival by including (Jemperli) with the typical paclitaxel/carboplatin (regimen), as well as incorporating a maintenance strategy for up to three years. I believe this is really important as it provides a more long-term option for treatment that may allow patients to live longer with limited or resolved disease. “

Jemperli was previously approved by the FDA in February as a standalone treatment of patients with recurrent or advanced dMMR endometrial cancer whose disease progressed following treatment with a platinum-containing regimen and are not eligible for curative surgery or radiation.

“This (second approval) also helped to expand the amount of patients that could have access to this drug, and showing that it significantly improved the time that it took for the cancer to come back, as well as the overall survival of these patients across all populations,” said Chapman-Davis.

According to the findings published in the New England Journal of Medicine, the most common side effects experienced by patients that occurred or got worse during the cause of treatment were nausea (53% of patients treated with Jemperli and 45.9% of those treated with chemotherapy alone), alopecia (53.5% and 50%, respectively) and fatigue (51.9% and 54.5%, respectively).

According to the American Cancer Society, potential side effects for immunotherapy treatments (drugs that help a patient’s immune system identify and kill cancer cells) such as Jemperli include fatigue, weakness, fever, cough, nausea, itching, rash, loss of appetite, muscle or joint pain, shortness of breath, constipation and diarrhea, as well as autoimmune reactions in the lungs, intestines, liver, hormone-producing glands, skin, kidneys or other organs.

“Once you added (Jemperli) to the chemotherapy, it did not cause more aggressive toxicities than the standard chemotherapy,” Chapman-Davis said. “The role of immunotherapy treatments are to try utilize our own immune response to help attack cancer cells. But sometimes you can have toxicities that are specific to your bodies intense immune response including pulmonary toxicity, skin toxicity, or thyroid toxicity but these are reactions that we can monitor every cycle. Many immune related toxicities were things that were very easily treatable and were consider low grade. There were very low instances of what we call grade three or four toxicities that would make patients get off of the drug, which is what we really care about.”

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