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 HER2-positive GC/GEJC cohort.

Abstract

e16034 Background: BAT8010 is an ADC argeting 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 gastric/gastroesophageal junction cancer 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 5, 2026, 34 HER2-positive GC/GEJC patients were enrolled, with a median of 2 prior lines of therapy, 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 34 patients who received at least one dose of BAT8010 in combination with BAT1006, at least one treatment-emergent adverse event (TEAE) was reported in 32/34 (94.1%) patients. The most common TEAEs (≥25%) were neutropenia, leukopenia, anemia, thrombocytopenia, elevated alanine aminotransferase, hypoalbuminemia, diarrhea, and infusion-related reaction (IRR). Most TEAEs were Grade 1/2; however, Grade 3 or higher AEs were reported in 68.8% of patients, including neutropenia (22/34, 64.7%), leukopenia (10/34, 29.4%), thrombocytopenia and anemia (each 5/34, 14.7%). No cases of interstitial lung disease (ILD)/pneumonitis were reported. Efficacy: Among 34 patients with at least one tumor assessment, 15 achieved PR and 18 SD, yielding an ORR of 44.1% (15/34) and a DCR of 97.1% (33/34); the mPFS was 7.52 months (95% CI: 4.53–NR).The overall survival (OS) data remain immature due to insufficient follow-up duration. Conclusions: BAT8010 in combination with BAT1006 is well-tolerated with manageable toxicity, and demonstrates promising preliminary antitumor activity in HER2-positive GC/GEJC. 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 .