Efficacy, Safety, and Immunogenicity of HLX02 Compared with Reference Trastuzumab in Patients with Recurrent or Metastatic HER2-Positive Breast Cancer: A Randomized Phase III Equivalence Trial

Abstract

Background HLX02 is an approved biosimilar of trastuzumab. Objective This study aimed to evaluated the efficacy, safety, and immunogenicity of HLX02 compared with reference trastuzumab in patients with human epidermal growth factor receptor 2 (HER2)-positive recurrent or metastatic breast cancer.Patients and Methods This randomized, double-blind, phase III study was conducted at 89 centers in China, the Philippines, Poland, and Ukraine. Eligible patients were randomized (1:1) to receive HLX02 or European Union (EU)-sourced trastuzumab (initial dose of 8 mg/kg, followed by 6 mg/kg every 3 weeks for up to 12 months) in combination with docetaxel intravenously. The primary endpoint was overall response rate up to week 24 (ORR 24 ). Equivalence was declared if the 95% confidence interval (CI) of difference was within ± 13.5%. Safety and immunogenicity were evaluated in patients who received at least one dose of study medication. Results Between 11 November 2016 and 10 July 2019, a total of 649 patients were enrolled. The ORR 24 was 71.3 and 71.4% in the HLX02 (n = 324) and EU-trastuzumab (n = 325) groups, with a difference of − 0.1% (95% CI − 7 to 6.9), which fell entirely in the predefined equivalence margins. No statistically significant differences were observed in all secondary efficacy analyses. Safety profiles and immunogenicity were comparable in HLX02 and EU-trastuzumab groups. In total, 98.8% of patients in each group experienced at least one treatment-emergent adverse event (TEAE), 23.8 and 24.9% experienced serious TEAEs, and 0.6% in each group had antidrug antibodies. Conclusions Among patients with HER2-positive recurrent or metastatic breast cancer, HLX02 demonstrated equivalent efficacy and similar safety and immunogenicity to reference trastuzumab.

Targeting mTOR and Glycolysis in HER2-Positive Breast Cancer

“…Recently, a biosimilar to trastuzumab, HLX02 [75], was shown to have near-identical clinical results when compared to trastuzumab [76]. Xu et al [59] reported that HXL02 showed similar efficacy and adverse effects in patients with HER2-positive recurrent or metastatic breast cancer compared to patients receiving trastuzumab (Table 1).…”

Biosimilar monoclonal antibodies in China: A patent review

“…The availability of Zercepac® changed actuality. Produced by Henlius, Zercepac® is the first biosimilar of trastuzumab and has obtained all the indications that Herceptin® (trastuzumab) has been approved in China due to the pleasure results of clinical trials (NCT02581748, NCT03084237, ; CTR20160526, [ 81 ].,[ 82 ] Up to 2021, 18 biosimilars of trastuzumab and pertuzumab have entered the competition of anti-HER2 biosimilar.…”

Biosimilars in an Era of Rising Oncology Treatment Options

“…In terms of clinical development, there were some differences in clinical study design across Phase III trials of different trastuzumab biosimilars. In the case of ABP 980 (Kanjinti R ; Amgen), CT-P6 (Herzuma R ; Celltrion) and SB3 (Ontruzant R ; Samsung Bioepis), Phase III trials were conducted in HER2-positive early breast cancer (using pCR as a primary end point), whereas MYL-1401O (Ogivri R ; Mylan), PF-05280014 (Trazimera R ; Pfizer) and HLX02 (Zercepac R ; Shanghai Henlius Biotech) Phase III trials were conducted in the first-line metastatic breast cancer setting, with ORR as the primary clinical end point [46,47]. Study indications, primary end points and prespecified equivalence margins for each trastuzumab biosimilar development campaign are shown in Table 1.…”

“…BS: Biosimilar; N/A: Not applicable; ORR: Objective response rate; pCR: Pathological complete response; RP: Reference product. Created using data from[46,47].…”