Multicenter phase 3 trial of first-line serplulimab plus chemotherapy with or without HLX04 versus chemotherapy in advanced nonsquamous NSCLC

The phase 3 ASTRUM-002 at 72 centers in China evaluated serplulimab (anti-PD-1) plus HLX04 (bevacizumab biosimilar) and chemotherapy in nonsquamous NSCLC. Patients aged 18-75 years with locally advanced or metastatic nonsquamous NSCLC without EGFR sensitising mutations or ALK/ROS1 rearrangements and without previous systemic therapy were 1:1:1 randomized to receive serplulimab plus HLX04 and chemotherapy (pemetrexed and carboplatin (group A; n=212), serplulimab plus chemotherapy plus HLX04 placebo (group B; n=214), or chemotherapy plus serplulimab placebo plus HLX04 placebo (group C; n=210). Primary endpoint was blinded independent central review assessed progression-free survival. Median duration of follow-up was 23 months. Median PFS was 12.6 months in group A, 11.0 months in group B, and 5.6 months in group C. A significant reduction in risk of progressive disease or death was seen in group B compared with group C (HR 0.55; p<0.0001). No significant improvement in PFS was seen in group A compared with group B (HR 0,86; p=0.25). Treatment-related serious events occurred in 39% of patients in group A, 37% in group B, and 24% in group C; whereas grade 3 or worse TRAEs occurred in 71%, 66%, and 57%, respectively; and grade 5 TRAEs occurred in 5%, 2%, and 3%, respectively. The authors conclude that addition of serplulimab to chemotherapy led to significantly longer PFS in patients with LA/M nonsquamous NSCLC compared with chemotherapy alone. Addition of HLX04 to serplulimab and chemotherapy did not confer further statistically significant benefit.