The proposed biosimilar MYL-1402O (Abevmy; Viatris and Biocon Biologics) met predefined criteria for biosimilarity to reference bevacizumab in a phase 3 trial in patients with stage IV nonsquamous non–small cell lung cancer (nsNSCLC).

The authors noted that lung cancer is the most common cause of cancer-related mortality in the United States and worldwide. Bevacizumab, a monoclonal antibody to vascular endothelial growth factor A, retards blood vessel development that supports tumor growth. The reference product (Avastin) was approved to treat metastatic colorectal cancer by the FDA in 2004 and the European Medicines Agency (EMA) in 2005. Today, bevacizumab is authorized for multiple indications, including in combination with platinum-based chemotherapy as a first-line treatment for patients with advanced or recurrent nsNSCLC.

In many cancers, bevacizumab-based regimens have improved overall survival (OS) and progression-free survival (PFS); however, patient access can be limited due to high out-of-pocket costs, the authors said. Bevacizumab “has become an integral, standard-of-care component for many malignancies,” and biosimilars, which are often lower-cost alternatives to reference products, could improve access.

Previous studies have established the analytical and pharmacokinetic similarity of MYL-1402O to reference bevacizumab. The current study evaluated efficacy, safety, and immunogenicity of MYL-1402O compared with the reference product in combination with carboplatin and paclitaxel (CP) chemotherapy in patients with stage IV nsNSCLC.

The study included 671 patients from 102 sites in 17 countries. After randomization, patients were treated with reference bevacizumab or the biosimilar plus CP for up to 18 weeks (6 cycles), followed by monotherapy with the reference drug or the biosimilar for up to 24 weeks.

Similar Overall and Progression-Free Survival Rates

The primary end point was overall response rate (ORR) at 18 weeks. The authors, noting “the FDA and the EMA use different approaches to determine equivalence based on the ORR,” reported ORR consistent with both FDA (ratio of ORR) and EMA (difference in ORR) requirements.

Overall, 41.5% and 43.1% of patients in the biosimilar and originator groups, respectively, had either a complete or partial response at 18 weeks. Efficacy based on ORR was comparable between groups. The ratio of ORR between groups was 0.96 (90% CI, 0.83-1.12) and the difference in ORR between groups was –1.6 (90% CI, –9.0 to 5.9). The 90% confidence intervals were within predefined margins for biosimilarity. The authors noted “the ORR data reported here are within the range of ORR reported in published data for the reference product.”

Subgroup analyses were carried out based on age, sex, race, smoking status, number of metastasis sites, prior radiation therapy, Eastern Cooperative Oncology Group status, negative or unknown sensitizing epidermal growth factor receptor mutation, negative or unknown sensitizing EML4-ALK rearrangement, and geographical region. Overall, the authors said, these results supported equivalence between the treatment groups; however, when the number of metastasis sites was limited to 1 and patients had had prior radiation therapy, there was evidence of a “slightly lower response” in the biosimilar group.

The investigators reported that secondary efficacy end points, including PFS, OS, disease control rate, and duration of response at 18 weeks and 42 weeks were comparable between groups. For example, the median PFS at 42 weeks was 7.6 months (95% CI, 7.0-9.5) in patients treated with MYL-1402O and 9.0 months (95% CI, 7.2-9.7) in patients treated with reference bevacizumab.

Adverse Events “Within the Expected Range”

On safety, the authors wrote, “the frequency, type, and severity of treatment-emergent adverse events (TEAEs) and AEs of interest were comparable between MYL-1402O and reference bevacizumab, falling within the expected range of the type and severity previously described in other bevacizumab biosimilar studies.”

Most patients (92.8% in the biosimilar group and 92.4% in the originator group) reported at least 1 TEAE during the study. The authors noted there were 8 (2.4% of patients) and 5 (1.5% of patients) TEAEs leading to death in the biosimilar and reference product groups, respectively, considered to be related to bevacizumab treatment. They also noted there was a higher incidence of serious TEAEs during the bevacizumab-plus-CP treatment period compared with the bevacizumab monotherapy period.

The investigators observed “no notable differences” between groups in treatment-emergent antidrug antibodies (ADAs), with 6.5% of patients treated with MYL-1402O and 4.8% of patients treated with the originator positive for ADAs. The incidence of neutralizing antibodies was lower in the biosimilar group (0.6%) compared with the originator group (2.5%).

The authors concluded MYL-1402O is therapeutically equivalent to bevacizumab in combination with CP, based on ORR by both FDA and EMA requirements. They added that their results support extrapolation to all applicable conditions for bevacizumab, because bevacizumab “has the same mechanism of action across all indications and the dose used for NSCLC is highest among all approved indications.”

In December, Tot Biopharm said it has been granted regulatory approval for a bevacizumab biosimilar (Pusintin) by China’s National Medical Products Administration.

Reference

Socinski MA, Waller CF, Idris T, et al. Phase III double-blind study comparing the efficacy and safety of proposed biosimilar MYL-1402O and reference bevacizumab in stage IV non-small-cell lung cancer. Ther Adv Med Oncol. Published online November 18, 2021. doi:10.1177/17588359211045845