Dostarlimab Gains Breakthrough Therapy Designation for dMMR/MSI-H Rectal Cancer

The US Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to dostarlimab-gxly (dostarlimab) for the treatment of patients with locally advanced mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) rectal cancer.

The Breakthrough Therapy designation is based on positive results from an ongoing phase II collaborative trial between GSK and Memorial Sloan Kettering Cancer Center. While the current standard of care for patients with dMMR/MSI-H locally advanced rectal cancer consists of initial chemotherapy and radiation followed by surgery, nearly one-third of patients still die due to distant metastasis.

Results of the trial have shown a 100% clinical complete response (cCR) rate in all 42 patients with frontline locally advanced dMMR rectal cancer who underwent treatment with dostarlimab. Each patient had no evidence of tumors upon investigation using magnetic resonance imaging, endoscopy, PET scan and digital rectal exam.

The first 24 patients evaluated in the study had a sustained cCR rate with a median follow-up of 26.3 months (95% CI: 12.4-50.5). The treatment’s safety and tolerability profile was consistent with its known safety profile.

Findings of this ongoing trial are set to be confirmed by the phase II registrational AZUR-1 trial, evaluating the efficacy and safety of dostarlimab in patients with previously untreated locally advanced dMMR/MSI-H rectal cancer. Dostarlimab was previously granted a Fast Track designation for patients with dMMR/MSI-H rectal cancer in January 2023.