Bevacizumab Biosimilar Candidate TAB008 Comparable to Reference Bevacizumab for Patients With Locally Advanced, Metastatic EGFR Wild-Type Non-Squamous NSCLC

In a phase 3 similarity study, bevacizumab biosimilar candidate TAB008 was found to be similar to reference monoclonal antibody bevacizumab in terms of efficacy, safety, and pharmacokinetic parameters for patients with locally advanced, metastatic EGFR wild-type non-squamous non-small cell lung cancer (nsNSCLC).

Bevacizumab, which targets the vascular endothelial growth factor (VEGF) has shown promising efficacy in many cancers, both implemented alone and in combination with chemotherapy and/or immunotherapy. “This study compared the efficacy and safety of TAB008 with [bevacizumab] sourced from the EU (bevacizumab-EU), in patients with non-squamous non-small cell lung cancer,” S. Lu, MD, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China and coauthors wrote.

This randomized, double-blind, multicenter study enrolled 549 patients who were treatment-naïve for EGFR wild-type, locally advanced, metastatic, or recurrent nsNSCLC. Patients were randomized on a 1-to-1 basis to receive either TAB008 (n = 277) or reference bevacizumab (n = 272). Patients received 15 mg/kg TAB008 or bevacizumab intravenously, plus paclitaxel/carboplatin for 4 to 6 cycles, followed by 7.5 mg/kg TAB008 or bevacizumab until disease progression, unacceptable toxicity or death. The primary end point compared the objective response rate (ORR) within 6 cycles, as reviewed by an independent radiological review committee. The secondary end points 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 were evaluated by the study investigators.

In the full analysis set, ORRs were 55.957% in the TAB008 arm and 55.720% in the bevacizumab arm, and the ORR ratio was 1 (90% confidence interval [CI], 0.89 to 1.14), which fell 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% respectively, 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 occurred in 37.55% (104 out of 277) of patients in the TAB008 arm and 34.32% (93 out of 271) in the bevacizumab arm. Anti-drug antibodies were reported in 3 out of 277 (1.08%) patients in the TAB008 arm, and 5 of 271 (1.85%) patients in the bevacizumab arm. Neutralizing antibody was discovered to be positive in 1 patient on bevacizumab, which became negative upon follow-up.

“TAB008 is similar to [bevacizumab] in terms of efficacy, safety, and pharmacokinetic parameters, with comparable immunogenicity,” the study authors concluded.

Source:

Lu SL, Qin S, Zhou Z, et al. 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. J Cancer Res Clin Oncol. Published online January 3, 2023. doi:10.1007/s00432-022-04563-4