TAPISTRY: A Phase II Study of Atezolizumab in Patients with Tumor Mutational Burden-High Tumors.

[PURPOSE] Patients with tumor mutational burden (TMB)-high tumors can derive benefit from atezolizumab, though previous studies have used inconsistent TMB cutoffs. We report data for atezolizumab in patients with TMB-high solid tumors from the phase II TAPISTRY multicohort trial, using TMB cutoffs of ≥13 and ≥16 mutations per megabase (mut/Mb).

[PATIENTS AND METHODS] Patients with PD-L1 inhibitor-naïve, TMB-high (≥13 mut/Mb), advanced/metastatic solid tumors received atezolizumab every 21 days [1,200 mg for adults, 15 mg/kg (up to 1,200 mg/kg) for children]. The primary endpoint was independent review committee (IRC)-assessed objective response rate (ORR) for TMB ≥16 mut/Mb. Secondary endpoints (using TMB ≥13 mut/Mb) included IRC-assessed ORR, duration of response (DOR), progression-free survival (PFS), and safety.

[RESULTS] As of November 9, 2023 (median survival follow-up: 9.8 months), 148 patients received treatment. Median age was 63 years, 31.8% of patients had >2 prior therapy lines, and the most common tumor types were colorectal (29.1%), breast (8.8%), and gastroesophageal (8.8%). IRC-assessed ORR was 22.3% [95% confidence interval (CI), 15-31.2] with TMB ≥16 mut/Mb (n = 112), and 20.2% (95% CI, 13.6-28.1) with TMB ≥13 mut/Mb (n = 129). Median IRC-assessed DOR was not estimable. Median IRC-assessed PFS was 2.8 (95% CI, 1.7-5.4) and 2.7 (95% CI, 1.5-4.2) months using TMB ≥16 and ≥13 mut/Mb, respectively. Adverse events were reported in 93.2% of patients, of which 53.4% were treatment-related (no grade 5) and 40.5% were grade ≥3.

[CONCLUSIONS] Atezolizumab led to moderate antitumor activity in various TMB-high solid tumors. Safety was consistent with previous reports.