Atezolizumab treatment of tumors with high tumor mutational burden from MyPathway, a multicenter, open-label, phase IIa multiple basket study

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Abstract

High tumor mutational burden (TMB-H) correlates with improved immunotherapy response. We assessed atezolizumab 1200-mg every 3 weeks for TMB-H tumors from MyPathway (NCT02091141), a phase 2a multi-basket study. One hundred twenty-one patients had advanced solid tumors with TMB {greater than or equal to}10 mut/Mb by any CLIA assay. The pre-planned primary endpoint was objective response rate (ORR) in patients with TMB {greater than or equal to}16 mut/Mb tumors by FoundationOne TMB testing (F1[CDx]). Patients with F1(CDx) TMB {greater than or equal to}10 and <16 mut/Mb were also evaluated. Ninety patients with 19 tumor types and F1(CDx) TMB {greater than or equal to}10 mut/Mb were efficacy-evaluable. In 42 patients with F1(CDx) TMB {greater than or equal to}16 mut/Mb, confirmed ORR was 38.1% (16/42, 95% CI 23.6-54.4) and disease control rate was 61.9% (26/42, 95% CI 45.6-76.4), versus 2.1% (1/48, 95% CI 0.1-11.1) and 22.9% (11/48, 95% CI 12.0-37.3) for 48 patients with TMB {greater than or equal to}10 and <16 mut/Mb. Responses were observed in nine different tumor types (47% [9/19]).