Dostarlimab monotherapy in mismatch repair deficient solid tumors

The GARNET trial, recently published on JAMA Network Open, demonstrated that dostarlimab, a recently approved immune checkpoint inhibitor, could be a well-tolerated treatment option with rapid, robust and durable antitumor activity in patients with a range of diverse Mismatch repair deficiency(dMMR) solid tumors.
Tumors with dMMR and/or high microsatellite instability have been found to have increased tumor-infiltrating lymphocytes and increased expression of PD-1 receptor and its ligands; simultaneously, the microsatellite instability-driven oncogenic pathway leads to a high tumor mutational burden, with highly immunogenic neoantigens arising from frameshift mutations. Together, these features make these dMMR and microsatellite instability-high tumors attractive candidates for anti–PD-1 and anti–PD-L1 checkpoint inhibition. The GARNET study is a phase I nonrandomized trial investigating the immune checkpoint inhibitor dostarlimab (500 mg intravenously every 3 weeks for 4 doses) in 327 patients with dMMR solid tumors (43% endometrial cancer, 32% colorectal cancer), who had been treated with at least one previous line of therapy. At a medianfollow-up of 27.7 months, results showed an objective response rate of 44%; 72% of responders had a response lasting 12 or more months; median progression-free survival was 6.9 months and the probability of progression-free survival at 24 months was 40.6%. Safety was consistent with the drug class and no new safety signals were observed. «Advanced cancer that has progressed on or following prior chemotherapy with or without targeted therapy is typically associated with poor outcomes. The antitumor activity data presented here support the use of dostarlimab monotherapy in patients with dMMR solid tumors and provide evidence on the durability of response in this setting. Dostarlimab provided clinically meaningful long-term benefit with a tolerable safety profile in dMMR solid tumors with a high unmet need», authors conclude.