The US Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to a cancer drug called dostarlimab (brand name Jemperli) that has so far shown a 100 percent clinical response rate for the treatment of locally advanced mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) rectal cancer.
“Today’s designation, which is based on the unprecedented 100% clinical complete response rate of dostarlimab reported to date, supports a path to help change the treatment paradigm for patients with locally advanced dMMR/MSI-H rectal cancer, who face long-term adverse quality-of-life effects. Our registrational AZUR-1 trial is continuing to study dostarlimab in this patient population.” Said Hesham Abdullah, Senior Vice President, Global Head of Oncology, R&D at GSK.
What is breakthrough therapy designation?
Breakthrough Therapy designation by the FDA is intended to speed up the development and review of drugs that target serious medical conditions, especially when early clinical evidence suggests the drug offers substantial improvements over existing treatments.
What is dMMR/ MSI-H rectal cancer?
In the US in 2024, there were over 152,000 new cases of colorectal cancer – a group of cancers which rectal cancer falls into – which accounted for 7.6 percent of all new cancer cases.
In 5-15 percent of colorectal cancers, there is a mismatch repair machinery and high microsatellite instability (dMMR/MSI-H), abnormalities that affect the DNA repair when it is copied in a cell. The dMMR/MSI-H status can be used as a biomarker that can help predict the response to an immune checkpoint blockade with a programmed death receptor-1 (PD-1) therapy.
How does the drug work?
Jemperli is a PD-1-blocking monoclonal antibody used as an immunotherapy treatment that improves the immune system’s ability to attack and eradicate cancer cells. This drug can help eradicate rectal cancer tumors without the need for chemotherapy, radiation therapy, or surgery – standard treatments that can often have significant, long-term side effects.
In an ongoing phase II trial – involving patients with dMMR/MSI-H rectal cancer and supported by GSK – all 42 patients who completed the treatment had a 100 percent clinical response, with only mild side effects, and the drug has been well tolerated.
Along with colorectal tumors, there are a few tumors that can be found with the dMMR/MSI-H biomarker, including gastrointestinal, endometrial, and other solid tumors. In the US, Jemperli has already been approved for use in patients with dMMR/MSI-H advanced or recurrent endometrial cancer, both as a standalone therapy (monotherapy) or in combination with chemotherapy.
Jemperli represents a potential game changer in oncology, offering a non-invasive treatment option that could transform outcomes for these rectal cancer patients while sparing them the side effects of traditional therapies.
Source Link: FDA Breakthrough Therapy Designation Granted For Promising Rectal Cancer Drug