Researchers, led by Birgit Geurts, conducted a clinical trial to evaluate the safety and efficacy of the PD-L1 inhibitor, durvalumab, in the treatment of various mismatch repair deficient (dMMR) or microsatellite instability-high (MSI-H) tumors from the Drug Rediscovery Protocol population.
According to the investigators, durvalumab exhibited a favorable safety and efficacy profile in advanced dMMR or MSI-H solid tumors from heavily pretreated patients who previously exhausted all other standard of care options.
However, the authors noted patients with high structural variant (SV) burden, JAK1 frameshift mutations, and low IFN-γ expression were associated with a reduced rate of clinical response. The findings were published in BMC Cancer.
The primary end point was the rate of patients achieving a clinical benefit, defined as objective response (OR) or stable disease for 16 weeks or more. Authors enrolled a total of 26 participants with 10 different types of cancer, of which 2 were not eligible for the primary analysis.
According to the report, 13 (50%) out of 26 patients demonstrated a clinical benefit with durvalumab, of which 7 (27%) were an OR. Investigators noted the remaining 11 (42%) of 26 patients displayed progressive disease. The population had a median progression-free survival of 5 months (95% CI, 2-not reached) and median overall survival of 14 months (95% CI, 5-not reached).
“Durvalumab provided durable responses in previously treated patients with advanced dMMR/MSI-H solid tumours,” the authors summarized. They added that their finding of potential resistance mechanisms warrants validation in larger studies.
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