A phase Ib/IIa study of BAT8010+BAT1006, an anti-HER2 monoclonal antibody-exatecan conjugate combined with an ADCC-enhanced HER2 mAb in patients with advanced solid tumors: Results from the 1L HER2-positive breast cancer cohort.

Abstract

1046 Background: BAT8010 is an ADC targeting HER2, while BAT1006 is a humanized monoclonal antibody targeting another epitope of HER2, with ADCC enhancement activity via completely devoid of fucose. Expansion cohort of 1st-line HER2-positive breast cancer (BC) patients enrolled, treated with BAT8010 + BAT1006. Methods: Patients in this open-label, multicenter clinical trial received BAT8010 + BAT1006 on day 1 of a 21-day cycle until intolerable or disease progression occurred. The study objectives included assessing tolerability, safety, pharmacokinetic characteristics, immunogenicity, and preliminary efficacy. Results: As of January 9, 2026, 46 HER2-positive BC patients were enrolled, and received BAT8010 2.4 mg/kg in combination with BAT1006 15 mg/kg. Favorable efficacy was observed with a manageable and predictable safety profile; dose optimization is ongoing in the BAT8010 2.1 mg/kg in combination with BAT1006 15 mg/kg dose cohort. Safety: Among the 46 patients who received at least one dose of BAT8010 in combination with BAT1006, at least one treatment-emergent adverse event (TEAE) was reported in 41/46 (89.1%) patients. The most common TEAEs (≥30%) were neutropenia, leukopenia, anemia, infusion-related reaction (IRR), thrombocytopenia, elevated alanine aminotransferase and diarrhea. Most TEAEs were Grade 1/2; however, Grade 3 or higher AEs were reported in 67.4% of patients, including neutropenia (27/46, 58.3%), leukopenia (16/46, 34.8%), and anemia (7/46, 15.2%). No cases of interstitial lung disease (ILD)/pneumonitis were reported. Efficacy: Among 46 patients with at least one tumor assessment, 1 patient achieved CR, 34 PR, and 11 SD, yielding an ORR of 76% (35/46) and a DCR of 100% (46/46); mPFS: not yet mature. Conclusions: BAT8010 in combination with BAT1006 is well-tolerated with manageable toxicity, and demonstrates promising preliminary antitumor activity in HER2-positive BC. Dose expansion studies in this patient population are ongoing, and further confirmatory clinical trials are planned to initiate for the additional validation of its safety and efficacy. Clinical trial information: NCT06376136 .