Efficacy and safety of first China-manufactured trastuzumab biosimilar HLX02 for metastatic breast cancer: A phase III trial

Abstract

Abstract Background The introduction of trastuzumab in combination with chemotherapy has significantly improved clinical outcomes for patients with HER2-positive breast cancer. HLX02 was developed as a trastuzumab biosimilar with the potential to increase market competition and treatment accessibility in China and around the world. Methods We conducted a randomised, double-blind, parallel-controlled equivalence study (HLX02-BC01) at 89 study centres in China, Philippines, Poland and Ukraine. Eligible women were aged 18 years or older, had histologically confirmed HER2+ breast cancer, an Eastern Cooperative Oncology Group performance status of 0 to 1, and estimated life expectancy ≥3 months. Patients were randomised at 1:1 to receive an intravenous dose of 8\xa0mg/kg of HLX02 or EU-trastuzumab with docetaxel on Day 1 -Cycle 1 followed by a dose of 6\xa0mg/kg once every 3 weeks in 3-weekly cycles for up to a maximum of 12 months. The primary endpoint was best overall response rate at Week 24 (ORRwk24) evaluated by blinded central imaging review. Secondary endpoints included clinical benefit rate (CBR), disease control rate (DCR), duration of response (DoR), progression-free survival (PFS) and overall survival (OS), safety outcomes with immunogenicity and incidence of adverse events up to 12 months. Results Of 1046 patients enrolled, 649 were randomly allocated to receive HLX02 (n\xa0=\xa0324) or EU-trastuzumab (n\xa0=\xa0325). The ORR was 71.0% (230 of 324 patients; 95% CI: 66.0, 75.9) for HLX02 and 71.4% (232 of 325 patients; 95% CI: 66.5, 76.3) for EU-trastuzumab. The p-value at 95% CI (p\xa0=\xa00.952) was completely contained within the pre-defined equivalence boundaries of\xa0±\xa013.5%. The difference in ORR between the 2 treatments was 0.4 (95% CI: -7.4, 6.6). Safety outcomes and immunogenicity were similar between the treatment groups at Week 24. Conclusions Among women with HER2+ metastatic breast cancer, the use of HLX02 compared with EU-trastuzumab resulted in an equivalent ORR at Week 24. All secondary efficacy and safety analyses at Week 24 also supported the conclusion of therapeutic equivalence; HLX02 does not demonstrate new safety signals in comparison with EU-trastuzumab. Further study results at Month 12 will be reported in August once the study is unblinded. Clinical trial identification NCT03084237; EudraCT: 2016-000206-10. Legal entity responsible for the study Shanghai Henlius Biotech, Inc. Funding Shanghai Henlius Biotech, Inc. Disclosure B. Xu: Research grant / Funding (institution): Shanghai Henlius Biotech,Inc. Q. Zhang: Research grant / Funding (institution): Shanghai Henlius Biotech,Inc. T. Sun: Research grant / Funding (institution): Shanghai Henlius Biotech,Inc. W. Li: Research grant / Funding (institution): Shanghai Henlius Biotech,Inc. Y. Teng: Research grant / Funding (institution): Shanghai Henlius Biotech,Inc. X. Hu: Research grant / Funding (institution): Shanghai Henlius Biotech,Inc. I. Bondarenko: Research grant / Funding (institution): Shanghai Henlius Biotech,Inc. H. Adamchuk: Research grant / Funding (institution): Shanghai Henlius Biotech,Inc. L. Zhang: Research grant / Funding (institution): Shanghai Henlius Biotech,Inc. D. Trukhin: Research grant / Funding (institution): Shanghai Henlius Biotech,Inc. B. Li: Full / Part-time employment: Shanghai Henlius Biotech,Inc. B. Shan: Full / Part-time employment: Shanghai Henlius Biotech,Inc. J. Cheng: Full / Part-time employment: Shanghai Henlius Biotech,Inc. T. Peng: Full / Part-time employment: Shanghai Henlius Biotech,Inc. W. Jiang: Full / Part-time employment: Shanghai Henlius Biotech,Inc. S. Liu: Full / Part-time employment: Shanghai Henlius Biotech,Inc. X. Zhang: Full / Part-time employment: Shanghai Henlius Biotech,Inc. Q. Wang: Full / Part-time employment: Shanghai Henlius Biotech, Inc. E. Liu: Full / Part-time employment: Henlix Biotech, Inc. A.Y. Luk: Full / Part-time employment: Shanghai Henlius Biotech,Inc.