388P - Biosimilar TAB008 compared with bevacizumab in advanced non-squamous, non-small cell, EGFR wildtype lung cancer patients

Background

Bevacizumab (Avastin®) is a monoclonal antibody targeting the vascular endothelial growth factor (VEGF). Used alone or in combination with chemotherapy and/or immunotherapy, there is confirmed efficacy in many cancers.

Methods

In this randomized, double-blind, multicenter, phase III, treatment naive, locally advanced, metastatic, or recurrent EGFR wildtype non-squamous, non small cell lung cancer (nsNSCLC) patients were enrolled and randomized (1:1) into TAB008 or Avastin® groups. Patients received 4-6 (3 week)cycles of paclitaxel/carboplatin plus TAB008 or Avastin® at 15mg/kg intravenously, followed by 7.5mg/kg maintenance dose 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 included disease control rate (DCR), duration of response (DoR), progression free survival (PFS), 1 year overall survival rate (OSR), overall survival (OS), safety, immunogenicity, and pharmacological bio-equivalence of C_min under steady state conditions.

Results

A total of 549 nsNSCLC patients were enrolled (277 in the TAB008 group, 272 in the Avastin® group). In the full analysis set, ORRs were 55.957% for TAB008, and 55.720% for Avastin®, the 90% CI was 0.89-1.14, well within the predefined equivalence margin of 0.75-1.33. No significant differences were found in DCR within 6 cycles (95.7% vs 95.4%, 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 OSR (66.2 vs 68%, p=0.6793), or OS (20.4 vs 17.4 months, p=0.6594). Serious adverse events (AEs) occurred in 37.55% (104/277) and 34.32% (93/271) in the TAB008 and Avastin® groups. Anti-drug antibodies were reported in 3/277 (1.08%) and 5/271(1.85%) in the TAB008 and Avastin® groups. Steady-state trough concentrations (C_min) were 106.13 and 96.03μg/mL in the TAB008 and Avastin® groups, with the treatment group ratio of LS geometric means is contained within the bioequivalence limits of 80.00–125.00% (90% CI: 101.74%-120.05%).

Conclusions

TAB008 is similar to bevacizumab(Avastin®) in terms of efficacy, safety, and pharmacokinetic parameters.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

TOT BIOPHARM.

Funding

TOT BIOPHARM.

Disclosure

X. Li, L. Wang: Full/Part-time employment: TOT BIOPHARM. All other authors have declared no conflicts of interest.