Atezolizumab with carboplatin plus nab-paclitaxel combination therapy for TTF-1 negative advanced nonsquamous non–small cell lung cancer: A multicenter, single-arm phase 2 trial (F1NE TUNE, LOGiK 2102)

BACKGROUND: Individuals with thyroid transcription factor-1 (TTF-1)-negative nonsquamous non-small cell lung cancer (NSCLC) have a poor prognosis. There have been no prospective studies targeting TTF-1-negative nonsquamous NSCLC. METHODS: This multicenter, single-arm phase 2 study enrolled chemotherapy-naïve individuals with TTF-1-negative advanced nonsquamous NSCLC to receive four cycles of atezolizumab in combination with carboplatin plus nab-paclitaxel, followed by atezolizumab alone. The primary endpoint was progression-free survival (PFS). RESULTS: Between June 2022 and March 2024, 52 patients (41 male and 11 female) with a median age of 68.0 years were enrolled. Thirty-three patients had adenocarcinoma and 19 had nonadenocarcinoma. Nineteen, 30, and 3 patients were current, former, and never-smokers, respectively. The PD-L1 tumor proportion score was < 1 % in 22 cases, 1-49 % in 18 cases, ≥ 50 % in 11 cases, and unknown in 1 case. The median PFS was 4.9 months (80 % confidence interval [CI], 4.3-5.9 months). The lower limit of the 80 % CI did not exceed the prespecified threshold of 4.5 months; therefore, the study did not meet its primary endpoint. The median overall survival was 13.2 months (95 % CI, 10.3-27.2 months). The response rate was 56.9 % (95 % CI, 43.3-69.5 %). There were no new safety signals. CONCLUSIONS: This first prospective study of individuals with TTF-1-negative advanced nonsquamous NSCLC has provided evidence for the efficacy and safety of the combination of carboplatin plus nab-paclitaxel with atezolizumab in such patients. The prognosis of TTF-1-negative advanced nonsquamous NSCLC remains poor, however, warranting further treatment development.