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INTRODUCTION Biological therapies such as bevacizumab have improved survival in patients with non-small-cell lung cancer (NSCLC). This study was conducted to confirm equivalent efficacy of the biosimilar candidate BI 695502 to bevacizumab reference product (RP). METHODS In this phase III, multicenter, randomized, double-blind trial, adult patients with recurrent or metastatic NSCLC received up to 18 weeks of induction treatment with BI 695502 or bevacizumab RP 15 mg/kg plus paclitaxel and carboplatin. Subsequent maintenance therapy comprised BI 695502 or bevacizumab RP monotherapy until disease progression or unacceptable toxicity. The primary endpoint was best overall response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 assessed by central imaging review, until 18 weeks after the start of treatment. RESULTS In total, 671 patients were randomized 1:1 to BI 695502 or bevacizumab RP, of whom 335 and 328, respectively, received treatment. Of these, 228 (68.1%) and 256 (78.0%), respectively, proceeded to maintenance monotherapy. A manufacturing issue led to a small number of patients treated with BI 695502 switching to bevacizumab RP late in the study. The primary endpoint, best ORR, was 54.0% in the BI 695502 group and 63.1% in the bevacizumab RP group. The 90% confidence interval for the between-group ratio of best ORR (0.770–0.951) was within the pre-specified range for equivalence (0.736–1.359). Adverse events were class-related and similar between the two treatment arms. CONCLUSIONS This study demonstrated equivalent ORR after 18 weeks of treatment with BI 695502 or bevacizumab RP, with similar adverse event profiles.

This Phase I trial (INVICTAN®-1) evaluated three-way bioequivalence and safety of BI 695502 a bevacizumab biosimilar candidate, and reference product bevacizumab from two sources (US-approved Avastin®, Genentech; EU-approved Avastin, Roche).Healthy male subjects (N = 91) were randomized 1:1:1 to receive a single intravenous infusion of 1 mg/kg of BI 695502 or US- or EU-approved Avastin. An interim analysis was planned when ~50% of subjects were evaluable for the primary end point to determine if the prespecified criteria for bioequivalence were achieved; if demonstrated, the study could be stopped early. The primary end point was area under the concentration-time curve (AUC) of the analyte in plasma from time zero extrapolated to infinity (AUCThe interim analysis demonstrated three-way bioequivalence for all comparisons. The confidence intervals around the geometric mean ratios of the primary and secondary PK parameters were within the predefined acceptance ranges. Study drugs were well tolerated with no clinically relevant differences in safety.BI 695502 and US- and EU-approved Avastin showed three-way bioequivalence with similar safety profile.NCT01608087.