FDA Accepts BLA for Pertuzumab Biosimilar in HER2+ Breast Cancer

The FDA has accepted for a review a biologics license application (BLA) seeking the approval of HLX11, an investigational biosimilar referencing pertuzumab (Perjeta), in the treatment of select patients with HER2-positive breast cancer.1

Pertuzumab is currently indicated by the FDA for use in combination with trastuzumab (Herceptin) and docetaxel for treatment of patients with HER2-positive metastatic breast cancer who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease; and in combination with trastuzumab and chemotherapy as the neoadjuvant treatment of patients with HER2-positive, locally advanced, inflammatory, or early stage breast cancer (either greater than 2 cm in diameter or node positive) as part of a complete treatment regimen for early breast cancer and as adjuvant treatment of patients with HER2-positive early breast cancer at high risk of recurrence.2

The BLA for HLX11 is supported by data from a randomized phase 1 trial (NCT04411550), which investigated the biosimilar vs pertuzumab derived from the United States (US), European Union (EU), and China in healthy Chinese males.1 It was also supported by data from a phase 3 trial (NCT05346224), which evaluated the biosimilar in combination with trastuzumab and docetaxel in patients with HER2-positive, hormone receptor (HR)–negative, early-stage or locally advanced breast cancer.

In the phase 1 study, patients were randomly assigned 1:1:1:1 to receive HLX11 or US-, EU-, or China-derived pertuzumab.3 Findings showed that the 90% CIs of the geometric mean ratios of were all within the prespecified equivalence margins for Cmax, AUC0-T, and AUC0-∞. Safety data showed the rates of adverse effects was similar between the 4 arms, and anti-drug antibodies and neutralizing antibodies did not affect pharmacokinetics.

The phase 3 study met its primary end point of pathological complete response (pCR) rate for HLX11 plus trastuzumab and docetaxel vs pertuzumab plus trastuzumab and docetaxel.4

The phase 3 study was a multicenter, double-blind, randomized, parallel-controlled, equivalence study that enrolled patients at least 18 years of age with histologically confirmed invasive breast carcinoma with a primary tumor size of more than 2 cm per local assessment.5 Study protocol allowed for the enrollment of patients with early-stage (T2-3, N0-1, M0) or locally advanced (T2-3, N2 or N3, M0; T4, any N, M0) disease. Centrally confirmed HER2-positive disease (immunohistochemistry 3+ or 2+/in situ hybridization positive) and HR-negative disease (less than 1% nuclear staining for the estrogen receptor and progesterone receptor) was required.

Other key inclusion criteria comprised a baseline left ventricular ejection fraction of at least 55% and adequate major organ function. Patients were excluded if they had inflammatory breast cancer; had stage IV, bilateral, or multicentric breast cancer; or had a history of other malignancies within 5 years, other than patients who received radical treatment of cervical carcinoma in situ, basal cell carcinoma, squamous cell carcinoma of the skin.

Investigators randomly assigned patients in a 1:1 fashion to receive HLX11 or pertuzumab in combination with trastuzumab and docetaxel. In the neoadjuvant setting, HXL11 and pertuzumab were given at a loading dose of 840 mg, followed by subsequent doses of 420 mg once every 3 weeks for up to 4 cycles. In the adjuvant setting, the agents were given at a loading dose of 840 mg, followed by subsequent doses at 420 mg once every 3 weeks for up to 13 cycles.

All patients also received neoadjuvant treatment with trastuzumab at loading dose of 8 mg/kg, followed by 6mg/kg, plus docetaxel at 75mg/m2 once every 3 weeks; and adjuvant treatment with doxorubicin at 60 mg/m2 and cyclophosphamide at 600 mg/m2 once every 3 weeks for 4 cycles, plus trastuzumab at a loading dose of 8mg/m2, followed by 6 mg/m2 once every 3 weeks for 13 cycles.

The trial’s primary end point was pCR rate. Breast pCR rate was a secondary end point.

References

1. US FDA accepts biologics license application (BLA) for HLX11, biosimilar candidate of Perjeta® (pertuzumab). News release. Shanghai Henlius Biotech. February 2, 2025. Accessed February 3, 2025. https://www.henlius.com/en/NewsDetails-4853-26.html
2. Perjeta. Prescribing information. Genentech; 2021. Accessed February 3, 2025. https://www.gene.com/download/pdf/perjeta_prescribing.pdf
3. 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
4. Phase 3 comparative clinical study of Perjeta (pertuzumab) biosimilar candidate HLX11. News release. Shanghai Henlius Biotech. September 30, 2024. Accessed February 3, 2025. https://www.henlius.com/en/NewsDetails-4726-26.html
5. 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://clinicaltrials.gov/study/NCT05346224