Bevacizumab biosimilar(Qilu Pharmaceutical Co., Ltd.)

This phase 3 study aimed to test equivalence in efficacy and safety for QL1101, a bevacizumab analogue in Chinese patients with untreated locally advanced non-squamous non-small cell lung cancer (NSCLC).

Eligible patients were randomly assigned 1:1 to receive carboplatin and paclitaxel in combination with either QL1101 or bevacizumab, 15 mg/kg every 3-week for 6 cycles. This was followed by maintenance treatment with single agent QL1101 every 3-week. The primary end-point was objective response rate (ORR), with secondary end-points being progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and adverse events (AEs).

Of 675 patients, 535 eligible patients were randomized to the QL1101 group (n = 269) and bevacizumab group (n = 266). ORRs were 52.8% and 56.8%, respectively, for the QL1101 and bevacizumab groups, with an ORR hazard ratio 0.93 (95% confidence interval: 0.8-0131.1). The PFS, OS, DCR, and AEs were comparable between the 2 groups, which remained the same after stratification according to epidermal growth factor receptor mutation or smoking history.

QL1101 showed similar efficacy and safety profiles as compared to bevacizumab among Chinese patients with untreated locally advanced non-squamous NSCLC.

This is the first study to compare the pharmacokinetics of QL1101, a proposed bevacizumab biosimilar, with Avastin® sourced from Roche Diagnostics GmbH.

In this double-blind, single-dose, parallel-group study, healthy male subjects were randomized 1:1 to receive QL1101 or Avastin® 3 mg/kg intravenously. Pharmacokinetic assessments were conducted for 85 days, with additional safety and immunogenicity assessments until day 90. Primary study endpoints were area under the concentration–time curve (AUC) from time zero to infinity (AUC0–∞), AUC from time zero to the last quantifiable concentration (AUC0–last), and maximum serum concentration (Cmax). Pharmacokinetic equivalence was shown if the 90% confidence intervals (CIs) of the geometric mean ratios (GMRs) of the C0–max, AUC0–last, and AUC0–∞ were within the predefined bioequivalence margin of 80–125.00%.

A total of 82 subjects were randomized to the following groups: 42 to QL1101 and 40 to Avastin®. The 90% CIs of the GMRs of AUC0–∞, AUC0–last, and Cmax of QL1101 and Avastin® were (97.8%, 107.0%), (94.5%, 106.9%), and (94.1%, 107.3%), respectively, which were all within the bioequivalence margin. The incidence of adverse events was 90.5% and 95.0% in the QL1101 and Avastin® groups, respectively. Mean serum concentration–time profiles, secondary pharmacokinetic parameters, and safety and immunogenicity profiles were comparable across the two treatment groups.

The study demonstrated the pharmacokinetic equivalence of QL1101 to Avastin®. QL1101 (3 mg/kg, iv) is safe and tolerable in healthy Chinese subjects. These data support the further clinical evaluation of QL1101 as a bevacizumab biosimilar.