Bevacizumab biosimilar candidate TAB008 compared to Avastin ® in patients with locally advanced, metastatic EGFR wild-type non-squamous non-small cell lung cancer: a randomized, double-blind, multicenter study

Background: Bevacizumab(Avastin ® ) is a monoclonal antibody targeting the vascular endothelial growth factor (VEGF). Used alone or in combination with chemotherapy and/or immunotherapy, bevacizumab has shown promising efficacy in many cancers. This study compared the efficacy and safety of TAB008 with bevacizumab(Avastin ® ) sourced from the EU (bevacizumab-EU), in patients with non-squamous non–small cell lung cancer (nsNSCLC). Method: In this randomized, double-blind, multicenter, phase III similarity study, treatment naive, EGFR wild-type, locally advanced, metastatic, or recurrent non-squamous, non-small cell, lung cancer (ns-NSCLC) patients were enrolled and randomized (1:1) into TAB008 or Bevacizumab-EU groups. Patients received TAB008 or bevacizumab-EU 15 mg/kg intravenously plus paclitaxel/carboplatin for 4-6 cycles followed by TAB008 or bevacizumab-EU 7.5 mg/kg until disease progression, unacceptable toxicity or death. The primary endpoint compared the objective response rate (ORR) within 6 cycles as read by an independent radiological review committee (IRRC). Secondary endpoints compared disease control rate (DCR) Within 6 cycles, duration of response (DoR), progression free survival (PFS), a year overall survival rate (OSR), overall survival (OS), safety, immunogenicity, and steady state pharmacokinetics. Results: : A total of 549 nsNSCLC patients were enrolled (277 in TAB008 group and 272 in Avastin ® group). In the full analysis set, ORRs were 55.957% for TAB008 and 55.720% for Avastin ® , the ORR ratio was 1 (90% CI 0.89-1.14), well within the predefined equivalence margin of 0.75 to 1.33. No significant differences were found in DCR within 6 cycles（95.703% vs 95.367%, p=0.8536）, DoR (8.17 vs 7.3 months, p=0.3526), PFS (9.10 vs. 7.97 months, p=0.9457), 1 year overall survival rate (66.2% vs 68%, p=0.6793), or OS (20.4 vs 17.6 months, p=0.6549). Serious adverse events (SAEs) occurred in 37.55% (104/277) of patients in the TAB008 group and 34.32% (93/271) in the Avastin ® group. Anti-drug antibodies were reported in 3 of 277(1.08%) TAB008 patients, and 5 of 271(1.85%) Avastin ® patients, neutralizing antibody (Nab) was positive in 1 patient on Avastin ® , which became negative upon follow-up. The steady-state trough concentrations (C ssmin ) were 106.13μg/mL in TAB008 group and 96.03μg/mL in Avastin ® groups, with the treatment group ratio of LS geometric means fully contained within the bioequivalence limits of 80.00–125.00% (90% CI was 101.74%-120.05%). Conclusions: : TAB008 is similar to bevacizumab-EU in terms of efficacy, safety, and pharmacokinetic parameters, with comparable immunogenicity. ClinicalTrials.gov number, NCT05427305）