Noticia de Contratación

The anti–vascular endothelial growth factor (anti-VEGF) agent bevacizumab (Avastin) carries indications for lung cancer, colorectal cancer, breast cancer, and glioblastoma, and has been the target of multiple hopeful biosimilar challengers. Alongside this week’s 2019 annual meeting of the American Society of Clinical Oncology (ASCO), 3 developers reported on their progress with developing biosimilars of this anticancer agent.

ABP 215 (Mvasi)
The first bevacizumab biosimilar to be approved by the FDA and authorized by the European Commission, ABP 215 (Amgen’s Mvasi), earned the FDA’s clearance on the basis of data that included findings from the phase 3 MAPLE study, which compared the biosimilar to the reference in patients with advanced non-squamous non–small-cell lung cancer (NSCLC).

During the ASCO meeting, researchers reported on the totality of the evidence on ABP 215 that led to approval.1

The researchers compared VEGF-A kinetic parameters for common isoforms: 121, 165, and 189. They determined that binding to all 3 isoforms was similar for the biosimilar and the reference product.

Patients were randomized to receive the biosimilar (n = 328) or the reference (n = 314) with carboplatin and paclitaxel for up to 6 cycles, and efficacy was based on objective tumor assessments. The primary efficacy endpoint was the risk ratio of objective response rate (ORR), and clinical equivalence was confirmed if the 2-sided 90% confidence interval (CI) of the risk ratio was within the prespecified margin of 0.67 to 1.5.

Based on a central analysis, ORR was achieved in 39.0% patients in the biosimilar arm and in 41.7% of patients in the reference arm (ORR risk ratio, 0.93 [90% CI, 0.80-1.09]). Based on an investigator analysis, ORR was achieved in 47.9% of patients in the biosimilar arm and in 48.1% of patients in the reference arm (ORR risk ratio, 1.01 [90% CI, 0.88-1.16]).

These results, write the authors, further confirm the similarity of ABP 215 to its reference, and support the extrapolation to all available indications for bevacizumab.

IBI305
Innovent provided greater detail on its phase 3 comparative study in patients with NSCLC after having announced positive topline results of the study in December 2018.

In the newly reported data, Innovent said that 450 patients with NSCLC who were receiving first-line treatment with carboplatin and paclitaxel were randomized to receive either the proposed biosimilar (n = 224) or the reference bevacizumab (n = 226) until progression.2

The primary endpoint was ORR, evaluated by comparing the 2-sided 90% CI of the RR between the study arms. The prespecified equivalence margin was 0.75-1.33.

ORR in the full analysis set was 44.3% in the biosimilar arm and 46.4% in the reference arm; the risk ratio for ORR was 0.95 (90% CI, 0.803-1.135), which fell within the prespecified margin.

Median PFS was 8.4 months in the biosimilar arm and 8.3 months in the reference arm. Treatment-emergent adverse events were balanced between arms and consistent with the known profile of bevacizumab.

The incidence of anti-drug antibodies (ADAs) was 0.5% in the biosimilar arm and 0% in the reference arm, and no patients developed neutralizing antibodies.

MB02
Finally, researchers report that the STELLA trial of MB02, a proposed bevacizumab biosimilar being developed by mAbxience, is underway.3

The study is a multinational, double-blind, randomized, parallel-group equivalence study to compare the efficacy and safety of the biosimilar versus its reference, both in combination with plus chemotherapy, in patients with stage 3B to 4 NSCLC

Patients will be randomized to the biosimilar or the reference along with chemotherapy, and after 6 cycles, they will receive bevacizumab monotherapy every 3 weeks until progression, intolerance, death, withdrawal, or the end of the study. The primary objective is to compare the OR between arms at week 18. Progression-free survival and overall survival at weeks 18 and 52, safety, and immunogenicity will also be assessed.

A sample size of 600 was calculated to provide 89% power to show equivalence on a primary endpoint of risk ratio based on ORR, and 596 individuals have been recruited, say the investigators.