A Phase II Trial of Atezolizumab Plus Carboplatin Plus Pemetrexed Plus Bevacizumab in the Treatment of Patients with Stage IV Non-Squamous Non-Small Cell Lung Cancer: Big Ten Cancer Research Consortium (BTCRC)- LUN 17-139

The BTCRC-LUN 17-139 is a single arm phase II study which evaluated the combination of Atezolizumab plus Carboplatin plus Pemetrexed plus Bevacizumab in stage IV treatment naive non-squamous NSCLC. The median PFS and OS were 11.3m and 22.4m, respectively. Despite notably prolonged PFS, the primary endpoint was not met and PFS was not statistically significant compared to historical control. Introduction: LUN17-139 evaluated the safety and efficacy of Atezolizumab (A) plus Carboplatin (C) plus Pemetrexed (Pem) plus Bevacizumab (B) (ACBPem) in treatment naive patients with stage IV non-squamous non-small cell lung cancer (Ns-NSCLC). Patients and Methods: In this multicenter, single-arm phase II trial, all patients received A (1200mg, D1) + C (AUC 5, D1) + Pem (500-mg/m2, D1) + B (15-mg/kg D1) q3 week x4. If no PD (progressive disease), patients received maintenance ABPem until PD or intolerable side effects. The primary endpoint was progression-free survival (PFS). The positive PFS result was considered as PFS >6m (historical control). Secondary endpoints included objective response rate (ORR), disease control rate (DCR) defined by complete response (CR) + partial response (PR) + stable disease (SD) >= 2 months, overall survival (OS), and safety. Results: Thirty patients were enrolled from November 2018 to October 2020. The study was closed early due to 3 patient deaths, possibly related to treatment. Median age 64 (range 38-83); Men/Women 20/10; PD-L1 TPS < 1%/1-49%/ >= 50% (8/15/7). The median follow-up was 20.3 months ( 1-28.1). ORR 42.9% (95% CI, 24.5-62.8%), DCR 96.4% (95% CI, 81.7-99.9%). The median PFS and OS were 11.3m (5.5-14.9,P >.05) and 22.4m (22.4-NR), respectively. Four patients had G4 toxicity (anemia, febrileneutropenia, severe neutropenia, sepsis), and 3 patients had G5 toxicity (thromboembolism, sepsis, colonic perforation). Conclusion: ABCPem was associated with increased PFS compared to historical controls but this difference did not meet the statistical significance. Three on-treatment deaths and 5 thromboembolic events prompted early closure.