1339P - Efficacy and safety of MIL60, a bevacizumab biosimilar, in combination with paclitaxel/carboplatin in patients with advanced or recurrent non-squamous non-small cell lung cancer: A randomized, double-blind, multicenter phase III study

Background

MIL60 is a biosimilar of bevacizumab (BEV) which can bind and inhibit vascular endothelial growth factor. We compared the efficacy, safety, popular pharmacokinetics (PoP PK) and immunogenicity of MIL60 with BEV in patients with advanced or recurrent non-squamous non-small cell lung cancer (NSCLC).

Methods

In this phase III, randomized, double-blind study (NCT03196986), we randomized assigned (1:1) patients with untreated advanced, or recurrent NSCLC to receive MIL60 or BEV (15 mg/kg on day 1 of each cycle every 3 weeks) in combination with paclitaxel/carboplatin, followed by MIL60 single-agent (7.5mg/kg) maintenance treatment until disease progression, or intolerable toxicity. The primary endpoint was the objective response rates at week 12 (ORR₁₂) by independent review committee (IRC) using RECIST 1.1.

Results

Between Aug 23, 2017, and Aug 1, 2019, 517 patients were randomly assigned to MIL60 group (n=257) and BEV group (n=260). In the full analysis population, the ORR₁₂ in MIL60 group and BEV group were 48.6% and 43.1%, respectively. The ORR ratio of these two groups were 1.14 (90% CI 0.97-1.33), which fell within the pre-specified equivalence boundaries (0.75-1/0.75). Analyses of secondary endpoints were based on updated data on October 31, 2020. The median DOR was 5.7 months (95% CI 4.5-6.2) for MIL60 and 5.6 months (95% CI 4.3-6.4) for BEV. No significant difference was noted in median PFS (7.2 vs. 8.1 months; HR 1.01, 95% CI 0.78-1.30, p=0.9606) and OS (19.3 vs. 16.3 months; HR 0.81, 95% CI 0.64-1.02, p=0.0755). Safety and tolerability profiles were similar between the two groups. Incidence of treatment-emergent adverse events (TEAE) grade ≥3 [70.3% (180/257) vs. 72.6% (188/260)] and serious adverse events (SAE) [28.1% (72/257) vs. 28.6% (74/260)] were also comparable in the MIL60 and BEV groups. Anti-drug antibody (ADA) was undetectable both in MIL60 and BEV groups.

Conclusions

MIL60 and BEV are equivalent in clinical efficacy in non-squamous non-small cell lung cancer patients, and the safety, Pop PK and immunogenicity of MIL60 was similar with BEV.

Clinical trial identification

NCT03196986; 23 June 2017.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Betta Pharmaceuticals Co., Ltd.

Disclosure

All authors have declared no conflicts of interest.