Phase 2 study of dostarlimab for mismatch repair-deficient, locally advanced rectal cancer

Neoadjuvant chemotherapy and radiation followed by surgical resection of the rectum is a standard treatment for locally advanced rectal cancer (LARC). A subset of rectal cancer is caused by a deficiency in mismatch repair (dMMR). Because dMMR colorectal cancer is responsive to PD-1 blockade in the context of metastatic disease, checkpoint blockade could be effective in patients with dMMR LARC. A phase 2 study at Memorial Sloan Kettering Cancer Center and Yale University School of Medicine evaluated neoadjuvant dostarlimab for dMMR LARC. All patients had clinical complete response. No patients received chemoradiotherapy or underwent surgery, and no cases of progression were seen during follow-up (range 6 to 25 months). No adverse events of grade 3 or higher were reported.