3. 1865 - Comparative Pharmacokinetics of a Proposed Biosimilar Bevacizumab Bmab-100 and Reference Product Bevacizumab in a Multicentre Double Blind Randomized Clinical Trial in Metastatic Colorectal Carcinoma (mCRC) Patients. (158P)
- Date: Nov 1st, 2017
- Authors: S. Beniwal, M. Kothekar, S. Loganathan, A. Vishweswaramurthy, A. Marwah, E. Pennella, N. Sengupta
Abstract –
Background: The availability of biosimilars may provide more affordable treatment options for patients with cancer. Bmab-100 is a proposed bevacizumab biosimilar.
Methods: This multicentre double blind randomized active controlled parallel design study comparing Bmab-100 and Avastin®, was performed in 136 first line mCRC patients [129 in pharmacokinetic (PK) population]. The primary objective of the study was to demonstrate PK bioequivalence of Bmab-100 and Avastin following a single dose based on primary PK parameters: AUC0-t and Cmax, evaluated after dosing in Cycle 1. Patients were randomized to Bmab-100 or Avastin arm and received bevacizumab at 7.5 mg/kg along with XELOX (oxaliplatin and capecitabine) chemotherapy for up to 6 cycles. Each cycle consisted of a 21-day period. Twelve PK samples were collected during Cycle 1 for the assessment of primary PK parameters. A validated Enzyme Linked Immunosorbent Assay was used for the quantitation of Avastin and Bmab-100 in patient serum samples.
Results: The study included 84 male and 52 female patients of Asian origin and the demographic profile was similar in the Bmab-100 and Avastin arms with respect to age, height, weight, body surface area and survival expectancy. The primary PK parameters were similar for both the products; demonstrated by the point estimates of the ratio (%) of least square means of natural log-transformed Cmax and AUC0-t of Bmab-100 to reference product bevacizumab [Cmax: 92.91% and AUC0-t (AUC 0-504): 95.79%]. In addition, the 90% CIs were within the pre-defined bioequivalence range of 80% to 125% (Cmax: 85.86 and 100.54%; AUC0-504: 87.56% and 104.79%), confirming the single dose PK equivalence of Bmab-100 and Avastin. No suspected unexpected serious adverse reactions were observed during the study.
Conclusions: These results establish the single dose PK bioequivalence of Bmab-100 and Avastin and in addition to the comparable disease control rate, immunogenicity observed in the study, strongly support the prospective for Bmab-100 as an affordable biosimilar bevacizumab.
Funding: Biocon Research Limited (a subsidiary of Biocon Limited), India and Mylan GmbH, Switzerland
