Results of a phase 3 trial of bevacizumab biosimilar candidate FKB238 suggest the monoclonal antibody is comparable in efficacy and safety to the reference product (RP), Avastin, in patients with advanced/recurrent nonsquamous non–small cell lung cancer (non-sq-NSCLC).
FKB238 is a pipeline drug from Centus Biotherapeutics, a joint venture between AstraZeneca and Fujifilm Kyowa Kirin. FKB238 (Equidacent) is approved for marketing in the European Union but remains under review by the FDA. In April 2021, Centus reached a settlement with Genentech over alleged US patent infringement related to FKB238.
In AVANA, patients were randomized 1:1 to intravenous infusions of FKB238 or RP at a dosage of 15 mg/kg. All patients received infusions of paclitaxel 200 mg/m2 and carboplatin for 4 to 6 cycles prior to receiving the bevacizumab agents. Patients received bevacizumab on day 1 of each 21-day cycle until disease progression or discontinuation of therapy.
The primary end point was overall response rate (ORR), which investigators described as a more appropriate measure of efficacy for biosimilar comparisons than overall survival (OS).
They chose a patient population with advanced/recurrent disease because this best matched the population for whom efficacy was demonstrated in the original study of Avastin.
The ORR rate was 51.6% in the FKB238 arm (n = 364) and 53.7% in the RP arm (n = 367). Estimated median progression-free survival (PFS) was 7.72 months in the FKB238 arm vs 7.62 months for the RP group (HR, 0.97; 95% CI, 0.82-1.16).
The occurrence of treatment-emergent adverse events (TEAEs) for patients receiving FKB238 vs RP was 94.2% and 95.1%, respectively. Investigators said 53.6% and 55.5% of patients in the FKB238 and originator arms experienced grade 3 or higher TEAEs, respectively.
Patients with non-sq-NSCLC typically present with inoperable, locally advanced, or metastatic disease, which is incurable, although with the introduction of kinase inhibitors and immune checkpoint inhibitors 5-year survival has improved to about 25%.
Serious TEAEs were experienced by 25.1% of patients in the FKB238 arm and 26.0% of patients in the RP cohort.
Patients with non-sq-NSCLC typically present with inoperable, locally advanced, or metastatic disease, which is incurable, although with the introduction of kinase inhibitors and immune checkpoint inhibitors, 5-year survival has improved to about 25%. Bevacizumab has been effective in prolonging PFS in non-sq-NSCLC. It is an angiogenesis inhibitor, meaning it retards the growth of blood vessels that feed tumor growth.
An earlier, phase 1 study of FKB238 demonstrated pharmacokinetic properties comparable to the originator product and good tolerance by patients, without antidrug antibody development.
In AVANA, median OS was 14.13 months for patients receiving FKB238 (95% CI, 12.52-16.56) and 16.95 months for patients in the RP arm (95% CI, 14.65-19.02). Investigators said 3% of patients in each arm tested positive for antidrug antibodies at any visit.
There are currently 2 bevacizumab biosimilars on the US market: Mvasi (Amgen) and Zirabev (Pfizer), launched in July 2019 and December 2019, respectively.