ABSTRACT Background Few treatment options are available for patients with epidermal growth factor receptor (EGFR) mutation‐positive metastatic non‐squamous non‐small cell lung cancer (NSCLC) who failed treatment with EGFR‐tyrosine kinase inhibitors (EGFR‐TKIs). We aimed to assess the efficacy and safety of atezolizumab plus bevacizumab in these patients. Methods We conducted a single‐arm, Simon's minimax two‐stage adapted phase II study. Patients received atezolizumab 1200 mg plus bevacizumab 15 mg/kg once every 3 weeks. The primary endpoint was the objective response rate (ORR). Secondary endpoints included duration of response (DOR), time to response (TTR), progression‐free survival (PFS), overall survival (OS), and safety. Results Between 14 August 2020 and 18 January 2021, 23 patients from seven sites in China were enrolled; all received study treatment. Twenty‐two patients were evaluable for ORR. At data cut‐off, median follow‐up was 16.4 months. The confirmed ORR was 18.2% (4/22) per RECIST v1.1. The number of responders did not cross the predefined threshold (> 6 patients) for stage II enrollment. For the four responding patients, the median TTR and DOR were 1.4 and 6.4 months, respectively. Median PFS and OS were 2.8 and 14.1 months, respectively. Atezolizumab plus bevacizumab had acceptable tolerability without any new safety signals identified. All patients experienced at least one treatment‐emergent adverse event (TEAE); four patients experienced serious TEAEs and one patient died of an unknown cause. Conclusions The chemotherapy‐free atezolizumab plus bevacizumab regimen had limited efficacy but an acceptable safety profile in this exploratory study. Although current data suggest that chemotherapy may still be important for patients who failed EGFR‐TKIs, more treatment regimens with lower toxicity and higher efficacy for these patients, such as antibody–drug conjugates and bispecific antibodies, need to be explored in the future. Trial Registration ClinicalTrials.gov identifier: NCT04426825
Fang et al. (2025) studied this question.