MAPLE Study Supports Clinical Equivalence of ABP 215 and Reference Bevacizumab

Amgen’s bevacizumab, ABP 215, is approved under the brand name Mvasi in both the United States and in the European Union as a biosimilar to the reference product, Avastin, though the biosimilar has not yet launched in either territory. This week, investigators published the results of the MAPLE study, a phase 3 trial of the biosimilar in comparison with the reference in patients with advance nonsquamous non—small cell lung cancer (NSCLC) who were also receiving first-line chemotherapy with carboplatin and paclitaxel.

In total, 642 patients with stage IV or recurrent metastatic disease were randomized to receive intravenous doses of either the biosimilar (n = 328) or the reference (n = 314). The primary efficacy end point was the risk ratio of objective response rate (ORR). Clinical equivalence of the primary end point was determined to be met if the 2-sided 90% confidence interval (CI) of the risk ratio in ORR between the biosimilar and the reference fell within the prespecified equivalence margin of 0.67 and 1.5.

The number of bevacizumab doses in the 2 treatment arms was similar, with the mean number of doses reaching 4.8 (standard deviation [SD], 1.76) in the biosimilar arm and 5.0 (SD, 1.61) in the reference arm.

In total, 128 (39.0%) patients in the biosimilar arm and 131 (41.7%) patients in the reference arm had objective responses. Two patients in each arm had complete responses. Progression-free survival and overall survival were comparable in both groups, and the risk ratio for ORR was 0.93 (90% CI, 0.80-1.09); the 2-sided 90% CI for ORR therefore fell within the prespecified margin for demonstrating clinical equivalence. Clinical equivalence was supported by comparing the risk difference (RD) of ORR between groups. The RD between treatment arms was —2.90% (90% CI, 9.2%-3.45%) in the intention-to-treat population based on central review.

In the biosimilar group, 85 patients (26.2%) had serious adverse events (AEs) versus 71 patients (23.0%) in the reference group. These AEs included febrile neutropenia, neutropenia, pneumonia, pulmonary embolism, anemia, dyspnea, and hemoptysis. In total, 24 patients (13 in the biosimilar arm and 11 in the reference arm) experienced a fatal AE during treatment.

Four patients (1.4%) in the biosimilar arm and 7 patients (2.5%) in the reference arm developed binding antidrug antibodies (ADAs) during the study. Three patients in each arm had transient binding ADAs. No patients tested positive to neutralizing antibodies.

The authors concluded that the study met its primary endpoint, that AEs were comparable between study arms, that immunogenicity was similar between arms, and that the MAPLE study “completes the totality of evidence recommended by regulatory agencies for biosimilars development.”

Reference

Thatcher N, Goldschmidt JH, Thomas M, et al. Efficacy & safety of biosimilar ABP 215 compared with bevacizumab in patients with advanced non—small cell lung cancer (MAPLE): a randomized, double-blind, phase 3 study [published online January 7, 2018]. Clin Cancer Res. doi: 10.1158/1078-0432.CCR-18-2702.