这次突破性疗法认定的授予主要基于一项由GSK支持并与纪念斯隆凯特琳癌症中心合作开展的2期临床试验的初步数据。试验显示，接受并完成dostarlimab作为一线疗法的42名局部晚期dMMR直肠癌患者，The USA FDA has granted breakthrough therapy designation (BTD) for its PD-1 inhibitor Jemperli (dostarlimab) for the treatment of locally advanced mismatch repair deficient (dMMR)/high microsatellite instability (MSI-H) rectal cancer.
According to the Zhitong Finance APP, GSK (GSK.US) recently announced that the USA FDA has granted its PD-1 inhibitor Jemperli (dostarlimab) breakthrough therapy designation (BTD) for the treatment of locally advanced mismatch repair deficient (dMMR)/high microsatellite instability (MSI-H) rectal cancer. This is the second regulatory designation for dostarlimab for the indication of locally advanced dMMR/MSI-H rectal cancer, following its qualification for fast track designation by the FDA in January 2023.
Rectal cancer is a type of colon cancer that originates in the rectum and is often classified as part of colorectal cancer. Colorectal cancer is the third most common cancer globally. In the USA, there are about 0.046 million new cases of rectal cancer diagnosed each year, of which about 5-10% are of the dMMR/MSI-H type. These tumors have replication errors due to abnormal DNA repair functions. Studies have shown that dMMR is an important biomarker that can predict the efficacy of PD-1 immune checkpoint inhibitor therapy. Tumors with this biomarker are typically found in endometrial cancer, colorectal cancer, and other gastrointestinal cancers, and may also appear in other types of solid tumors.
The granting of this breakthrough therapy designation is mainly based on preliminary data from a Phase 2 clinical trial supported by GSK and conducted in collaboration with Memorial Sloan Kettering Cancer Center. The trial showed that 42 patients with locally advanced dMMR rectal cancer who received and completed dostarlimab as a first-line therapy achieved an unprecedented 100% clinical complete response (cCR) rate, with no tumors detected by magnetic resonance imaging (MRI), endoscopy, positron emission tomography (PET), and digital rectal examination (DRE). In the first 24 patients, with a median follow-up time of 26.3 months (95% CI: 12.4-50.5), persistent cCR was observed.
