12P Atezolizumab plus bevacizumab and chemotherapy in EGFR-mutant NSCLC with acquired resistance: Final results from the randomised, non-comparative phase II ETOP ABC-lung trial

ABC-lung explores the potential synergistic effect of combining atezolizumab and bevacizumab with pemetrexed (ABPem) or carboplatin/paclitaxel (ABCPac) in pts with EGFR-mutant NSCLC, resistant to tyrosine kinase inhibitors (TKIs). ABC-lung is a 1:1 randomised, non-comparative, international phase II trial evaluating atezolizumab (1200 mg, Q3W) and bevacizumab (15mg/kg, Q3W) until progression (PD) with either carboplatin (AUC5, Q3W) and paclitaxel (175-200 mg/m2, Q3W) 4-6 cycles or pemetrexed (500 mg/m2, Q3W) until PD. The study was stratified by prior treatment with a 3rd-generation EGFR TKI and aimed to improve the 1-year (1y) progression-free survival (PFS) rate from 18% to 37%, assessed per RECIST v1.1 and tested separately in each arm. To reject the null hypothesis, at least 14 of 45 evaluable pts in each arm needed to be progression-free at 1y (power 83%, 1-sided a=0.023, exact binomial test). Secondary endpoints included overall survival (OS), objective response rate (ORR), PFS, quality of life (QoL) and adverse events (AEs). From 09/2020-09/2022, 95 pts were randomised to account for potential attritions: 45 to ABCPac, and 50 to ABPem. Median age was 62 years, 63% of pts were females, 60% never smokers, 55% Asians, 60% had an exon 19 deletion and 33%/66% had stage IVa/IVb NSCLC. From the 43 evaluable pts with ABCPac and the 45 with ABPem, 9 and 11 pts reached 1y without progression, respectively, missing the success criterion of 14 pts. The 1y PFS rate for randomised pts (median follow-up 19 months, m) was 25% for both ABCPac and ABPem, with median PFS of 6.4m and 7.6m, median OS of 15.4m and 15.6m and ORR of 47% and 32%, respectively. The median number of cycles for bevacizumab and atezolizumab was 8-9. Grade≥3 treatment-related AEs were experienced by 50% of pts with ABCPac and 42% with ABPem. There were no grade 5 AEs. Results from QoL and PD-L1 testing will be included in the presentation. The observed 1y PFS rate with atezolizumab, bevacizumab in combination with either carboplatin-paclitaxel or pemetrexed was similar in both arms and below the aspired rate of 37%. The safety is consistent with the known toxicity profiles.