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Randomized Controlled Trial
. 2023 Aug;149(9):5907-5914.
doi: 10.1007/s00432-022-04563-4. Epub 2023 Jan 3.

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

S Lu  1 , S Qin  2 , Z Zhou  1 , J Chen  3 , K Gu  4 , P Sun  5 , Y Pan  6 , G Yu  7 , K Ma  8 , J Shi  9 , Y Sun  10 , L Yang  11 , P Chen  12 , A Liu  13 , J He  14
Affiliations
Randomized Controlled Trial

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

S Lu et al. J Cancer Res Clin Oncol. 2023 Aug.

Abstract

Background: Bevacizumab (Avastin®) is a monoclonal antibody targeting the vascular endothelial growth factor (VEGF). Used alone or in combination with chemotherapy and/or immunotherapy, Avastin® has shown promising efficacy in many cancers. This study compared the efficacy and safety of TAB008 with 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 naïve for metastatic lung cancer., EGFR wild-type, locally advanced, metastatic, or recurrent non-squamous, non-small cell, lung cancer (nsNSCLC) patients were enrolled and randomized (1:1) into TAB008 or Avastin® groups. Patients received TAB008 or Avastin® 15 mg/kg intravenously plus paclitaxel/carboplatin for 4-6 cycles followed by TAB008 or Avastin® 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®, and the ORR ratio was 1 (90% CI 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 (95.703% 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 (Cssmin) were 106.13 μg/mL in TAB008 group and 96.03 μg/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 Avastin® in terms of efficacy, safety, and pharmacokinetic parameters, with comparable immunogenicity.

Trial registration: ClinicalTrials.gov number; NCT05427305.

Keywords: Avastin® biosimilar; EGFR wild-type; Non squamous non-small cell lung cancer (nsNSCLC); TAB008.

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Conflict of interest statement

The authors declare no potential conflicts of interest.

Figures

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Patient disposition
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Kaplan–Meier estimate of survival for PFS
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Incidence of treatment emergent adverse events of special interest
See this image and copyright information in PMC

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