FDA Accepts BLA of HLX02 for Patients With HER2-Expressing Cancers


Multiple trials and techniques have evaluated treatment with HLX02 compared with trastuzumab. Now, the FDA has accepted the biologics license application HLX02 for patients with HER2-overexpressing metastatic breast cancer, breast cancer, gastric cancer, and gastroesophageal junction adenocarcinoma.

The FDA has accepted a biologics license application (BLA) of HLX02 for the adjuvant treatment of HER2-overexpressing breast cancer, HER2-overexpressing metastatic breast cancer, and HER2-overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma, according to Accord BioPharma.1

HLX02 is a Chinese-manufactured trastuzumab (Herceptin) biosimilar currently approved in more than 30 countries. Trastuzumab is an anti-HER2 antibody given in combination with chemotherapy for patients with HER2-positive breast cancer. While the combination has significantly improved overall survival in these patients and has become the standard of care over the past decade, the cost can limit patient access.

The basis of this BLA submission comes from robust structural and functional analytical comparison data using multiple orthogonal techniques clinical studies between HLX02 and the reference agent, trastuzumab. These include comparative analytical studies, nonclinical studies, a phase 1 pharmacokinetic similarity study, and a global multicentric phase 3 study of HLX02 (NCT03084237) in patients with HER2-overexpressing metastatic breast cancer.2

According to data from these trials, treatment with HLX02 and trastuzumab lead to similar quality, safety, and efficacy data among these patient populations.

In the randomized, double-blind, phase 3 study, investigators evaluated the efficacy, safety, and immunogenicity of HLX02 vs reference trastuzumab in patients with HER2-positive recurrent or metastatic breast cancer.

The trial was conducted at 89 centers in China, the Philippines, Poland, and Ukraine and enrolled patients aged 18 years and older with histologically or cytologically confirmed adenocarcinoma of the breast who had recurrent disease not amenable to curative surgery or radiation therapy, or metastatic disease with an indication for a taxane-containing therapy and who had availability of formalin-fixed paraffin-embedded tissue block from the primary tumor, or a metastatic lesion, to confirm HER2-positivity by the central laboratory.2

Patients were eligible for the study if they had received no prior systemic anticancer agent, measurable disease, an ECOG performance status of 0-1, LVEF within institutional range of normal at baseline, an estimated life expectancy ≥3 months, and adequate hematologic, hepatic, and renal function.

The trial randomized patients in a 1:1 fashion to receive HLX02 or trastuzumab at an initial dose of 8 mg/kg, followed by 6 mg/kg every 3 weeks for up to 12 months in combination with docetaxel administered via intravenous infusion. A total of 649 patients were enrolled in the study between November 11, 2016, and July 10, 2019.3

Investigators assessed the primary end point of overall response rate (ORR) up to week 24 (ORR). Secondary end points of the study were ORR at Week 6, 12, 18, and 24, duration of response, disease control rate, clinical benefit rate, progression-free survival, and overall survival.

According to findings, the ORR at week 24 was 71.3% among patients treated with HLX02 (n = 324) and 71.4% for patients treated with trastuzumab (n = 325), with a difference of - 0.1% (95% CI, - 7 to 6.9). This fell entirely in the predefined equivalence margins.

In the secondary efficacy analyses, there were no statistically significant differences observed.

Looking at safety and immunogenicity, each profile was comparable between the HLX02 and trastuzumab groups. A total of 98.8% of patients in each arm experienced at least 1 treatment-emergent adverse event (TEAE). Additionally, 23.8% of patients given HLX02 and 24.9% given trastuzumab experienced serious TEAEs, and 0.6% in each group had antidrug antibodies.

Based on these findings which showed that patients with HER2-positive recurrent or metastatic breast cancer treated with HLX02 compared with trastuzumab had equivalent efficacy and similar safety and immunogenicity, the biosimilar has received this designation from the FDA and seeks to treat several types of HER2 cancers.

1. Accord BioPharma announces U.S. FDA acceptance of biologics license application for proposed biosimilar trastuzumab HLX02. News release. Accord BioPharma. April 5, 2023. Accessed April 5, 2023. https://prn.to/3KzoptP
2. Compare efficacy, safety and immunogenicity of HLX02 and Herceptin in previously untreated HER2 +overexpressing metastatic breast cancer. ClinicalTrials.gov. Updated June 7, 2022. Accessed April 5, 2023. https://clinicaltrials.gov/ct2/show/NCT03084237
3. Xu B, Zhang Q, Sun T, et al. 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. BioDrugs. 2021;35(3):337-350. doi:10.1007/s40259-021-00475-w
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