Several trials have verified that patients whose tumors overexpress PDL1 have improved clinical outcomes with anti-PD1 therapy. At the ASCO2015 Annual Meeting, Merck researchers report a new biomarker called mismatch repair (MMR) deficiency, which predicts superior response to anti-PD1 therapy.
Tumors with MMR deficiency harbor many more mutations than tumors without such repair defects. Whole exome sequencing revealed an average of 1,782 somatic mutations per tumor in MMR-deficient compared to 73 in MMR-proficient tumors. Tumors with more mutations are more likely to be recognized as foreign by the immune system.
In a Phase II trial of pembrolizumab, ORR was 62% in MMR-deficient patients (n=25) compared with 0% in MMR-proficient patients (n=25). Progression-free survival rates at 20 weeks were 78% and 11%, respectively. Merck plans to launch a larger phase II study to confirm these findings.
Approximately 5% of many tumor types have MMR deficiency. About 20% of non-inherited colorectal cancers are MMR deficient. MMR status could be easily determined using an existing commercially available test.