Abstract LB012: Efficacy of atezolizumab in the treatment of solid tumors with high tumor mutational burden (TMB): A MyPathway study cohort

Purpose Data suggest that TMB is correlated with response to checkpoint blockade. We present an analysis of atezolizumab treatment of patients (pts) with advanced solid tumors and high TMB from MyPathway (NCT02091141), a multi-basket study assessing activity of FDA-approved therapies in non-indicated tumors with targetable alterations. Methods Eligible pts were ≥18 years old with previously treated advanced solid tumors with TMB ≥10 mut/Mb by any CLIA-certified assay. Pts received atezolizumab 1200 mg IV q3w. The pre-planned primary endpoint was objective response rate (ORR) in pts with TMB ≥16 mut/Mb by FoundationOne CDx (F1CDx), a threshold determined by a retrospective study that showed TMB ≥16 mut/Mb is associated with improved ORR and duration of response (DOR) for various tumor types. Other endpoints in this group included disease control rate (DCR), DOR, progression-free survival (PFS), and overall survival (OS). Separate analyses were performed in pts with TMB ≥10 and Results Enrollment closed on 7-9-20. By the 12-11-20 data cutoff, 118 pts with 20 tumor types and TMB ≥10 mut/Mb by any CLIA assay were evaluable for efficacy. In the primary efficacy population of 42 pts with TMB ≥16 mut/Mb by F1CDx, confirmed investigator-assessed ORR was 38.1% vs 2.1% in 48 pts with TMB ≥10 mut/Mb and Conclusions Atezolizumab had durable activity against diverse solid tumor types with TMB ≥16 mut/Mb, independent of MSI status. Limited activity was observed in tumors with TMB ≥10 and Citation Format: John Hainsworth, Claire F. Friedman, Razelle Kurzrock, David R. Spigel, Howard Burris, Christopher J. Sweeney, Funda Meric-Bernstam, Yong Wang, Jonathan Levy, David Shames, Katja Schulze, Arisha Patel, Charles Swanton. Efficacy of atezolizumab in the treatment of solid tumors with high tumor mutational burden (TMB): A MyPathway study cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB012.