Proposed Bevacizumab Biosimilar for mCRC Found Noninferior to Reference Drug

The proposed bevacizumab biosimilar BE1040V was found to be noninferior to its reference product in terms of efficacy for the treatment of metastatic colorectal cancer (mCRC), according to a study published in Clinical Therapeutics.

Currently, 2 anticancer biosimilars referencing the originator, Avastin, are available in the US market: Mvasi, a bevacizumab biosimilar, and Kanjinti, a trastuzumab biosimilar referencing Herceptin, The Center for Biosimilars reports. However, in March, the FDA accepted a biologics license application (BLA) for MYL-1402O, a proposed biosimilar to bevacizumab.

“Bevacizumab works by inhibiting vascular endothelial growth factor-A, an angiogenic factor known to be overexpressed in tumors,” authors write.

A total of 126 patients with mCRC were enrolled in the phase 3 randomized, double-blind clinical trial. Participants were randomized 2 to 1 to receive either 5 mg/kg IV of the study drug plus Folfiri-3 (with repeated irinotecan 100 mg/m2 60-min infusion on day 3) or Avastin plus Folfiri-3 every 2 weeks for 1 year.

Colorectal cancer (CRC) ranks as the third-most commonly diagnosed cancer and the second-leading cause of cancer deaths in the world, while mCRC accounts for 20% to 25% of all CRCs.

In addition to the biosimilar being noninferior to its reference product, researchers also found tolerability was comparable between the 2 drugs. Although the primary end point of the trial was progression-free survival (PFS), overall survival (OS), objective response rate (ORR), time to treatment failure (TTF) and safety were also measured.

Researchers defined PFS as the time from the date of randomization to the first date of documented progression or death as a result of any cause. The per-protocol population was assessed for PFS, while sensitivity analyses were conducted on the intention-to-treat (ITT) population. Of the 126 study participants, 82 received BE1040V and 44 received Avastin.

In the per-protocol population:

• PFS values with BE1040V and the reference product were 232 days (7.7 months) and 210 days (7 months), respectively (P = .47)
• Hazard ratio (HR) of BE1040V versus the originator was calculated to be 0.79 (90% CI, 0.46—1.35; P = .47)

In the ITT population, HR for OS was 0.99 (95% CI, 0.55—1.80), and the difference between the 2 groups was not statistically significant (P = .99).

The study yielded the additional results:

• Median TTF with BE1040V was 73(9.39) days versus 73(9.12) days for Avastin, and the difference between the 2 groups was not statistically significant (P =.59)
• ORR values were reported to be 17 (40.48%) and 5 (21.74%) with BE1040V and the reference drug, respectively; the difference between the 2 groups was not statistically significant (difference = 0.19; 95% CI —0.04 to 0.41; P = .173)
• The rate of any grade 3/4 adverse events (AEs) were 23.75% and 27.27% in the BE1040V and reference drug groups, respectively

“Since the upper limit of 2-sided 90% CI was lower than the noninferiority margin of 1.44 [in the per-protocol population] BE1040V was considered to be noninferior to the reference drug,” the authors said. Complete response was seen in 1 patient in the BE1040V group and no significant differences in adverse events (AEs) were observed when comparing the 2 arms.

Authors note their study resulted in relatively lower PFS times compared with previous investigations. This may be attributable to differences in public health care between countries (the current study was carried out in Iran, and was conducted and funded by the maker of the proposed biosimilar), genetics, and environmental factors affecting life expectancy.

Due to short follow-up duration (up to 1 year), researchers could not report median OS in the present study.

Reference

Rezvani H, Mortazavizadeh SM, Allahyari A, et al. Efficacy and safety of proposed bevacizumab biosimilar BE1040V in patients with metastatic colorectal cancer: A phase III, randomized, double-blind, noninferiority clinical trial [published online April 22, 2020]. Clin Ther. doi: 10.1016/j.clinthera.2020.03.009.