Prospective clinical evaluation of blood-based tumor mutational burden (bTMB) as a predictive biomarker for atezolizumab (atezo) in 1L non-small cell lung cancer (NSCLC): Interim B-F1RST results.

12001 Background: TMB in both tissue and blood has shown promise in selecting for patients (pts) who clinically benefit from PD-L1/PD-1 inhibitors. In the randomized, 2L NSCLC Phase III OAK and Phase II POPLAR studies, high bTMB enriched for a PFS benefit in patients treated with atezo monotherapy. Here we report interim results from the single-arm, 1L NSCLC Phase II B-F1RST atezo monotherapy trial, which prospectively evaluated bTMB as a predictive biomarker for atezo using an NGS-based panel. Methods: Of 78 treated pts in the interim analysis population (IAP), 58 had adequate blood samples with sufficient detection of circulating tumor DNA (MSAF≥1%) and comprised the biomarker-evaluable population (BEP). A bTMB score of 16 (prevalence, 19% [11/58]) was prespecified to evaluate clinical efficacy in the BEP (bTMB high, ≥16; bTMB low, < 16). Statistical tests were 2-sided at a 0.1 level and 90% confidence interval. Results: Baseline characteristics were similar in the IAP and BEP. With a minimum follow-up of 6 mo, median PFS was 9.5 vs 2.8 mo for bTMB high vs low; HR, 0.49 (90% CI, 0.23, 1.04; P= 0.11). PFS HRs improved as bTMB scores increased (Table). In the BEP, the ORR was 12.1% (7/58) and disease control rate was 25.9% (15/58). In the bTMB high vs low groups, the ORR was 36.4% (4/11) vs 6.4% (3/47); odds ratio, 8.38 (90% CI, 2.02, 34.79; P= 0.02). Treatment-related serious AEs and treatment-related grade 3/4 AEs occurred in 14.1% and 16.7% of pts, respectively; 15.4% experienced AEs leading to discontinuation. Conclusions: PFS by various bTMB scores show preliminary utility of bTMB as a predictive biomarker for PFS and ORR, and further support bTMB selection of patients in the ongoing 1L BFAST study (NCT03178552). The safety profile in B-F1RST is consistent with the known AE profile for atezo. Additional biomarker and clinical data will be reported. B-F1RST is ongoing and has completed enrollment at 153 patients. Clinical trial information: NCT02848651.PFS (mo) by bTMB cutoff scores (BEP, n = 58). bTMB Score bTMB High Median (n) bTMB Low Median (n) HR 90% CI 12 3.0 (22) 3.2 (36) 0.95 0.55, 1.63 14 3.4 (14) 3.2 (44) 0.73 0.39, 1.39 16 9.5 (11) 2.8 (47) 0.49 0.23, 1.04 20 9.5 (8) 2.7 (50) 0.23 0.08, 0.62