GSK’s Jemperli in combination with chemotherapy shows improved overall survival in patients with endometrial cancer.
- Jemperli in combination with chemotherapy showed a 31% reduction in the risk of death and a 16.4-month improvement in median overall survival.
- Adding the PARP inhibitor Zejula to the Jemperli-chemotherapy combination reduced the risk of disease progression by 37% in mismatch repair proficient or microsatellite stable tumors population which required further treatment options.
The Latest
Originally used in combination with chemotherapy to treat endometrial cancer, the FDA has expanded Jemperli’s use to include patients with mismatch repair proficient or microsatellite stable tumors. This is following the release of GSK’s phase RUBY trial which found that Jemperli adjuvant to chemotherapy had a 31% reduction in the risk of death and a 16.4-month improvement in median overall survival compared to chemotherapy alone in the overall population regardless of the patient’s biomarker status. In the 2nd part of the RUBY trial, it was found that when the PARP inhibitor Zejula was added to the combination of Jemperli with chemotherapy, there was a 37% reduction in risk of disease progression or death and a 6-month improvement in median progression-free survival compared to chemotherapy alone in the mismatch repair proficient or microsatellite stable tumor populations.
Physician’s Perspective
Endometrial cancer is the 6th most common cancer in women. Of the tumors that arise, mismatch repair deficiency and microsatellite instability are observed in 25-30% of all endometrial cancers. While there are other PD-1 inhibitors on the market to treat endometrial cancers, Jemperli is the first to show an overall survival benefit. Additionally, it should be noted that while the results of the 2nd part of the RUBY trial are promising, in the past, PARP inhibitors have been linked to potential long-term detriments to subsets of ovarian cancer patients. GSK is still currently collecting long-term overall survival results of adding a PARP inhibitor to determine if the reduction in risk of disease progression translates into positive long-term overall survival results. The most serious side effects to be monitored that are associated with Jemperli include acute kidney injury, urinary tract infection, and severe abdominal pain.
Molecular Target of Therapy
Programmed cell death protein 1 (PD-1) is a cell surface receptor found on activated T cells and B cells that plays a crucial role in regulating immune responses. PD-1 interacts with its ligands, PD-L1 and PD-L2, which can be expressed on tumor cells, leading to the downregulation of T-cell activity and allowing cancer cells to evade immune detection. Jemperli (dostarlimab) is a humanized monoclonal antibody that binds with high affinity to the PD-1 receptor, blocking its interaction with PD-L1 and PD-L2. This blockade interferes with the PD-1 signaling pathway, thereby restoring T-cell function and enhancing the immune system’s ability to recognize and attack cancer cells.
Company History
Established in 2000 through a merger of Glaxo Wellcome and SmithKline Beecham, GSK is a large British pharmaceutical company. The company has a rich history of developing popular and well-known medications such as the Shingrix vaccine for the prevention of shingles, Ventolin for asthma, and Trelegy for COPD. GSK’s current drug pipeline is focused on oncology and respiratory disease.
Further reading: https://www.nejm.org/doi/full/10.1056/NEJMoa2216334
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