Neoadjuvant Pertuzumab Biosimilar HLX11 Versus Reference Pertuzumab for Early-stage or Locally Advanced Breast Cancer: A phase 3 Equivalence Trial.

PURPOSE: This randomized, double-blind phase 3 equivalence study aimed to evaluate the similarity of neoadjuvant pertuzumab biosimilar HLX11 versus reference pertuzumab plus trastuzumab and docetaxel for human epidermal growth factor receptor 2-positive, hormone receptor-negative early-stage or locally advanced breast cancer (BC). PATIENTS AND METHODS: Eligible patients were randomly assigned (1:1) to receive 4 cycles of neoadjuvant HLX11 (HLX11 arm) or European Union-sourced pertuzumab, plus trastuzumab and docetaxel (EU-pertuzumab arm). Patients in the respective arms received adjuvant HLX11 plus trastuzumab or were re-randomized (1:1) to receive HLX11 or EU-pertuzumab plus trastuzumab. The primary endpoint was blinded independent central review (BICR)-assessed total pathological complete response (tpCR) rate. RESULTS: In total, 908 patients were randomized to the HLX11 (n = 454) or EU-pertuzumab arm (n = 454); 192 patients in HLX11 arm received adjuvant HLX11; 200 patients in EU-pertuzumab arm were re-randomized to receive adjuvant HLX11 (n = 100) or EU-pertuzumab (n = 100). BICR-assessed tpCR rate (95% confidence interval [CI]) was 46.3% (41.6%-51.0%) and 45.8% (41.2%-50.5%), respectively. The equivalence criteria were met, with relative risk of tpCR (90% CI) of 1.01 (0.90-1.14) and relative difference (95% CI) of 0.47% (-5.99%-6.92%). No clinically meaningful differences were observed in other efficacy endpoints, safety, pharmacokinetics (PK), or immunogenicity. In the adjuvant phase, switching from EU-pertuzumab to HLX11 led to no notable differences in safety, PK, or immunogenicity. CONCLUSIONS: Compared with EU-pertuzumab, neoadjuvant HLX11 demonstrated a similar tpCR rate and no clinically meaningful differences in other efficacy endpoints, safety, PK, or immunogenicity in BC.