Serplulimab Plus Chemotherapy, with or without HLX04, versus Chemotherapy as First-Line Treatment for Nonsquamous...

Background: ASTRUM-002 met the primary endpoint of progression-free survival (PFS) with the combination of serplulimab plus HLX04 (bevacizumab biosimilar) and chemotherapy at interim analysis. Here, we report the results of the final survival analysis. Methods: A total of 636 patients with treatment-naïve, locally advanced or metastatic nonsquamous non-small cell lung cancer (nsq-NSCLC) without epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK)/ROS proto-oncogene 1 receptor tyrosine kinase (ROS1) genetic alterations were randomized 1:1:1 to receive serplulimab plus HLX04 and chemotherapy (group A), serplulimab plus HLX04 placebo and chemotherapy (group B), or double placebo plus chemotherapy (group C). Patients and the investigators were blinded to the group assignments. The primary endpoint was blinded independent central review-assessed PFS. Overall survival (OS) was the key secondary endpoint. Results: At the final analysis, median OS was 23.7 (95% confidence interval [CI] 20.5 to 27.5) months, 26.8 (95% CI 21.2 to 30.9) months, and 20.3 (95% CI 16.2 to 24.6) months in groups A (n = 212), B (n = 214), and C (n = 210), respectively. A significant reduction in risk of death for group B compared to group C was observed (hazard ratio [HR] = 0.66, 95% CI 0.52 to 0.83; P < 0.001). A total of 79 (37.6%) patients in group C had crossed over to serplulimab plus HLX04 treatment. Median OS in group C adjusted by the 2-stage model was 14.2 months (95% CI 11.9 to 17.0), corresponding to an adjusted HR of 0.53 (95% CI 0.42 to 0.68; P < 0.001) for group B versus group C. Using the rank-preserving structural failure time model, the adjusted median OS in group C was 17.9 months (95% CI 14.2 to 20.3), with a corresponding adjusted HR of 0.65 (95% CI 0.51 to 0.83; P < 0.001). No statistical difference in median OS for group A compared to group B (HR = 1.12, 95% CI 0.88 to 1.42; P = 0.363) was found. Conclusions: Serplulimab plus chemotherapy significantly prolonged OS and maintained PFS benefit compared to chemotherapy; however, the addition of bevacizumab biosimilar HLX04 did not yield further improvement for the first-line treatment of nsq-NSCLC without EGFR or ALK/ROS1 genetic alterations. Trial registration: This trial was registered at ClinicalTrials.gov (NCT03952403, date of registration: 2019 May 14).