Abstract

Purpose:
The purpose of this study was to compare the efficacy and safety of a proposed bevacizumab biosimilar to those of the reference
product in patients with metastatic colorectal cancer (mCRC).
Methods:
This Phase III, multicenter, randomized, double-blind (patient- and assessor-blind), active controlled, 2-armed, parallel group, noninferiority trial was conducted in patients with histologically verified colorectal cancer with evidence of at least 1 metastasis. Patients with mCRC were randomized 2:1 to receive 5 mg/kg IV of either study drug plus FOLFIRI-3 (with repeated irinotecan 100 mg/m2
60-min infusion on day 3) or the reference drug plus FOLFIRI-3 every 2 weeks for 1 year. Progression-free survival (PFS) was the primary end point, and overall survival, objective response rate, and time to treatment failure as well as safety and immunogenicity were
secondary end points. The population assessable for PFS was per protocol, and the intention-to-treat population was used for sensitivity
analysis. Safety was assessed based on reports of adverse events, laboratory test results, and vital sign measurements.
Findings:
A total of 126 patients were enrolled; PFS values in the biosimilar and reference arms were 232 days (7.7 months) and 210
days (7 months), respectively (P = 0.47). The hazard ratio of the biosimilar arm versus the reference arm was 0.79 in the per-protocol
population (90% CI, 0.46-1.35; P = 0.47). The upper limit for the 2- sided 90% CI was lower than the margin of 1.44, indicating that the
biosimilar drug was noninferior to the reference drug. The hazard ratio for overall survival in the intent-to-treat population was 0.99 (95% CI, 0.55-1.80; P = 0.99). The difference between other efficacy end points among the groups was not statistically significant. No significant difference was observed in the comparison of the two arms for safety. The antidrug antibody was positive in 1 patient in each arm.
Implications:
The proposed biosimilar BE1040V was noninferior to the reference product in terms of efficacy in the treatment of mCRC, and
tolerability was comparable between the 2 drugs.

Biography

Doctor Sina Salari was born in Tehran in 1973 and got accepted to Isfahan Medical University in 2000. In 2007 he completed his specialty
training in Internal Medicine at Tehran University and completed his 3 years fellowship in Hematology and Oncology at Shahid Beheshti
Medical University, graduating with distinction in 2012. He was appointed as “Assistant Professor” and “Faculty member” in 2013. His
responsibilities from 2013 to 2020 include the followings: Director of the deputy of treatment of Oncology-Hematology and BMT department, Physician in charge of the international patients’ department (IPD), Head of the internal department and responsible
authorized physician of Ayatollah Taleghani Hospital. Some of his achievements in his field are as below: Presenting variety of lectures
in national seminars, publishing more than 30 research articles in national and international journals, Attaining ESMO, ASCO, ASBMT,
and APBMT membership. Dr.Salari has a particular interest in gastrointestinal and breast cancer. He has also widely researched in
lymphoma and multiple myeloma treatments and Cell therapy. He is member of the Cancer-Immunotherapy scientific committee and
organized the first cancer Immunotherapy Congress in Shiraz in 2019.
Dr.Salari performed the first research on the Monoclonal Antibody drug “Rituximab” for treating patients with lymphoma in Iran in 2011.
He is also involved in most studies related to Biosimilar medicines for cancers, collaborating with Iran Food and drug administration as a
consultant. He wrote the first RCT paper on the biosimilar drug of “Stivant” which was published in the Clinical Therapeutics journal in
2020.

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