FDA Accepts BLA for Pertuzumab Biosimilar in HER2+ Breast Cancer

China’s National Medical Products Administration previously accepted a new drug application for HLX11 in combination with trastuzumab/chemotherapy for HER2-positive early breast cancer and with trastuzumab/docetaxel for HER2-positive metastatic or locally recurrent breast cancer in December 2024.

The FDA has accepted a biologics license application (BLA) for the investigational pertuzumab (Perjeta) biosimilar, HLX11, in various HER2-positive breast cancer populations, according to a press release from the developer, Shanghai Henlius Biotech, Inc.¹

Supporting data for the BLA came from a series of analytical similarity studies and clinical trials comparing treatment with HLX11 vs pertuzumab. Regarding the clinical trials, findings came from a phase 1 study (NCT04411550) evaluating the pharmacokinetics, immunogenicity, and safety of HLX11 vs pertuzumab in a healthy Chinese male patient population. Additionally, the BLA included data from a double-blind phase 3 trial (NCT05346224) assessing the safety and efficacy of each drug as neoadjuvant treatment for those with HER2-positive, hormone receptor (HR)–negative early, or locally advanced breast cancer.

Phase 1 Study

Findings published in BioDrugs showed that the pharmacokinetics, safety, and immunogenicity of HLX11 were comparable with those of reference pertuzumab as approved in the US, European Union (EU), and China.²

Compared with reference pertuzumab, HLX11 met the prespecified equivalence margins for all primary end points, which included maximum serum drug concentration, area under the serum concentration (AUC)–time curve from time 0 to time of last quantifiable concentration, and AUC from time 0 to infinity.

Treatment-emergent adverse effects (TEAEs) affected 95.6% of patients, which included 97.5% in the HLX11 arm, 97.5% in the US pertuzumab arm, 97.5% in the EU pertuzumab arm, and 90.0% in the China pertuzumab arm. Most toxicities were grade 1 or 2, and investigators noted that the incidence and severity of AEs were similar across treatment arms.

Investigators randomly assigned patients 1:1:1:1 to receive HLX11 (n = 40), US pertuzumab (n = 40), EU pertuzumab (n = 40), or China pertuzumab (n = 40) at 420 mg intravenously over 1 hour. The study’s secondary end points included pharmacokinetic parameters, safety, and immunogenicity.

Healthy male individuals who were 18 to 45 years old and Chinese with a body mass index of 19 to 26 kg/m² were eligible for enrollment on the study. Having any serious clinical disease, a history of drug abuse, or donation of blood within 3 months before beginning study treatment were grounds for exclusion from enrollment.

Phase 3 Study

Investigators of the multi-center, double-blind, parallel-controlled phase 3 trial announced that HLX11 reached the primary end point of total pathological complete response (tpCR) rate per independent review committee assessment in September 2024.³ At the time of analysis, investigators noted that evaluation was ongoing for the secondary end points of investigator-assessed tpCR rate, breast pathologic CR rate, objective response rate, event-free survival, disease-free survival, safety, pharmacokinetics, and immunogenicity.

An estimated population of 900 patients with HER2-positive, HR-negative early-stage, or locally advanced breast cancer were randomly assigned to receive neoadjuvant HLX11 or pertuzumab at a loading dose of 840 mg intravenously followed by 420 mg intravenously every 3 weeks.⁴ Additionally, all patients received treatment with trastuzumab (Herceptin) and docetaxel in the neoadjuvant setting as well as chemotherapy consisting of doxorubicin (Adriamycin) and cyclophosphamide.

Patients 18 years and older with histologically confirmed invasive breast carcinoma larger than 2 cm per standard local assessment, early-stage or locally advanced disease, and HER2-positive status based on central laboratory evaluation were eligible for enrollment on the trial. Those with inflammatory breast cancer, stage IV breast cancer, bilateral breast cancer, or multicentric breast cancer were ineligible for enrollment.

China’s National Medical Products Administration previously accepted a new drug application for HLX11 in combination with trastuzumab/chemotherapy for HER2-positive early breast cancer and with trastuzumab/docetaxel for HER2-positive metastatic or locally recurrent breast cancer in December 2024.⁵

References

1. US FDA accepts biologics license application (BLA) for HLX11, biosimilar candidate of Perjeta® (pertuzumab). News release. Shanghai Henlius Biotech, Inc. February 2, 2025. Accessed February 3, 2025. https://tinyurl.com/3pyufh7e
2. Yang J, Lin L, Long Q, et al. HLX11, a proposed pertuzumab biosimilar: pharmacokinetics, immunogenicity, and safety profiles compared to three reference biologic products (US-, EU-, and CN-approved pertuzumab) administered to healthy male subjects. BioDrugs. 2022;36(3):393-409. doi:10.1007/s40259-022-00534-w
3. Primary endpoint met in phase 3 comparative clinical study of Perjeta® (pertuzumab) biosimilar candidate HLX11. News release. Organon. September 30, 2024. Accessed February 3, 2025. https://tinyurl.com/yawb6vb4
4. A study to evaluate the efficacy and safety of HLX11 vs. EU-Perjeta® in the neoadjuvant therapy of HER2-positive and HR-negative early-stage or locally advanced breast cancer. ClinicalTrials.gov. Updated April 16, 2024. Accessed February 3, 2025. https://tinyurl.com/tzebtne6
5. China NMPA accepts Henlius' NDA for HLX11, an pertuzumab biosimilar candidate. News release. Shanghai Henlius Biotech, Inc. December 4, 2024. Accessed February 3, 2025. https://tinyurl.com/3ahessct