Background
Randomized, double-blind, phase 3 equivalence (biosimilarity) trial. N=908 with HER2-positive, hormone receptor-negative early-stage or locally advanced breast cancer receiving neoadjuvant therapy. HLX11 is a proposed biosimilar to reference pertuzumab, a humanized monoclonal antibody blocking HER2 dimerisation with HER3; dual HER2 blockade with trastuzumab plus pertuzumab and a taxane is standard neoadjuvant therapy. The trial was designed to demonstrate equivalence of total pathological complete response (tpCR), the accepted sensitive endpoint for detecting clinically meaningful differences between a biosimilar and its reference product.
Results
Interventions and follow up: Arm A: HLX11 plus trastuzumab and docetaxel ×4 neoadjuvant cycles (n=454)
Arm B: EU-sourced reference pertuzumab plus trastuzumab and docetaxel ×4 neoadjuvant cycles (n=454)
Adjuvant phase: 192 patients from the HLX11 arm continued adjuvant HLX11 + trastuzumab; 200 patients from the EU-pertuzumab arm were re-randomised 1:1 to adjuvant HLX11 (n=100) or continued EU-pertuzumab (n=100) to assess single transition/switching
Primary endpoint: tpCR rate by blinded independent central review (BICR)
Secondary endpoints: other efficacy endpoints, safety, pharmacokinetics, immunogenicity
mFollow up: NR
Results: tpCR (BICR, primary): 46.3% (95% CI 41.6-51.0) with HLX11 vs 45.8% (95% CI 41.2-50.5) with EU-pertuzumab
Relative risk of tpCR: 1.01 (90% CI 0.90-1.14) — within prespecified equivalence margins
Absolute difference in tpCR: 0.47% (95% CI -5.99 to 6.92)
Other efficacy endpoints: no clinically meaningful differences
Pharmacokinetics / immunogenicity: comparable between arms; single transition from EU-pertuzumab to HLX11 in the adjuvant phase produced no notable differences
Arm B: EU-sourced reference pertuzumab plus trastuzumab and docetaxel ×4 neoadjuvant cycles (n=454)
Adjuvant phase: 192 patients from the HLX11 arm continued adjuvant HLX11 + trastuzumab; 200 patients from the EU-pertuzumab arm were re-randomised 1:1 to adjuvant HLX11 (n=100) or continued EU-pertuzumab (n=100) to assess single transition/switching
Primary endpoint: tpCR rate by blinded independent central review (BICR)
Secondary endpoints: other efficacy endpoints, safety, pharmacokinetics, immunogenicity
mFollow up: NR
Results: tpCR (BICR, primary): 46.3% (95% CI 41.6-51.0) with HLX11 vs 45.8% (95% CI 41.2-50.5) with EU-pertuzumab
Relative risk of tpCR: 1.01 (90% CI 0.90-1.14) — within prespecified equivalence margins
Absolute difference in tpCR: 0.47% (95% CI -5.99 to 6.92)
Other efficacy endpoints: no clinically meaningful differences
Pharmacokinetics / immunogenicity: comparable between arms; single transition from EU-pertuzumab to HLX11 in the adjuvant phase produced no notable differences
Adverse events
Overall safety: no clinically meaningful differences between HLX11 and EU-pertuzumab; profile consistent with known pertuzumab plus trastuzumab plus docetaxel toxicity
Adjuvant switching: no notable differences in safety, PK, or immunogenicity after transition from EU-pertuzumab to HLX11
Detailed grade ≥3 rates: NR in the abstract
Adjuvant switching: no notable differences in safety, PK, or immunogenicity after transition from EU-pertuzumab to HLX11
Detailed grade ≥3 rates: NR in the abstract
Conclusions
Neoadjuvant HLX11 met prespecified equivalence criteria versus reference pertuzumab for BICR-assessed tpCR (46.3% vs 45.8%; RR 1.01), with comparable secondary efficacy, safety, PK, and immunogenicity, and no signal on single transition in the adjuvant phase. This is the registrational efficacy dataset behind the first pertuzumab biosimilar, and it establishes biosimilarity in the setting where dual HER2 blockade is most widely used.
Key Limitations
Equivalence trials answer a narrower question than superiority trials: tpCR is a short-term surrogate, and the study is not powered or designed to detect differences in event-free or overall survival, where any residual difference between products would ultimately matter. The design restricted enrolment to hormone receptor-negative disease, which has higher pCR rates and therefore greater assay sensitivity, but means HR-positive/HER2-positive patients — a large share of real-world pertuzumab use — were not studied directly. Only a single transition (EU-pertuzumab to HLX11) was tested, in 100 patients, so repeated or multiple switching is not addressed; immunogenicity signals from multiple switches would require larger and longer exposure. Neoadjuvant treatment was limited to 4 cycles, and follow-up duration for long-term outcomes was not reported. The comparator was EU-sourced pertuzumab, requiring an analytical/PK bridge to the US-sourced reference product.
Clinical Context
Pertuzumab (Perjeta) plus trastuzumab and a taxane is the standard neoadjuvant backbone for HER2-positive early breast cancer per NCCN, ASCO, and ESMO, based on NeoSphere, TRYPHAENA, and the adjuvant APHINITY data. HLX11 (US brand Poherdy) was approved by the FDA in November 2025 as the first pertuzumab biosimilar, with an interchangeability designation, and the EMA CHMP adopted a positive opinion in February 2026 recommending marketing authorisation across all reference-product indications. The clinical significance of this trial is therefore economic and access-related rather than a change in therapeutic strategy: biosimilar entry is expected to lower the cost of dual HER2 blockade and broaden access, following the pattern set by trastuzumab biosimilars. Clinicians should note that interchangeability is a US regulatory designation governing pharmacy-level substitution, not a claim of superiority.