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.

Abstract

1027 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. This study investigates the combination of BAT8010 and BAT1006 in patients with advanced solid tumors. 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 15, 2025, 20 patients with metastatic breast cancer (mBC, n=14) and gastric cancer (GC, n=6) were enrolled in three cohorts: BAT8010 (2.1mg/kg) + BAT1006, BAT8010 (2.4mg/kg）+ BAT1006 and BAT8010 (2.7mg/kg) + BAT1006, with BAT1006 fixed at 15 mg/kg. HER2 positivity on tumor tissue was categorized as IHC2+/FISH+ or IHC3+. Two dose-limiting toxicity (grade 4 thrombocytopenia and neutropenia) were reported in the BAT8010 (2.7mg/kg) + BAT1006 group. The maximum tolerated dose was determined to be BAT8010 (2.4mg/kg）+ BAT1006, and expansion studies have been proceeded at this dose. Safety: Among the 20 patients who received at least one dose of BAT8010 + BAT1006, 17/20 (85%) reported at least one treatment-emergent adverse events (TEAEs). The most common TEAEs (≥5%) included neutropenia, leukopenia, nausea, thrombocytopenia and anemia. Most TEAEs were Grade 1 or 2; however, 55% of the patients experienced Grade 3 or greater AEs, including neutropenia 7/20 (35%), thrombocytopenia 5/20 (20%), infusion-related reaction 1/20 (5%) and febrile neutropenia1/20 (5%). The infusion-related reaction was mild, and one subject discontinued the study treatment due to TEAEs. No cases of interstitial lung disease (ILD)/pneumonitis were reported. Efficacy: Fourteen mBC patients were recruited across the dose cohorts: BAT8010 (2.1 mg/kg)+BAT1006 (n=3), BAT8010 (2.4 mg/kg)+BAT1006 (n=7) and BAT8010 (2.7 mg/kg)+BAT1006 (n=4). Most had previously undergone 3-7 lines of systemic treatments, including trastuzumab and HER2 ADC regimens. Six GC patients were included in the BAT8010 2.4mg/kg + BAT1006 (n=4) and BAT8010 2.7mg/kg + BAT1006 (n=2) cohort. Sixteen patients had at least one tumor assessment, yielding an ORR of 43.7% (7/16) and a DCR of 87.5% (14/16). Among the 12 mBC patients, the ORR is 50% (6/12) with a DCR of 91.66% (11/12), including one CR. In the 4 GC patients, the ORR was 25% (1/4) with a DCR of 75% (3/4). Conclusions: The combination of BAT8010 and BAT1006 was well-tolerated, with manageable toxicity, and demonstrated promising preliminary antitumor activity in metastatic breast cancer and gastric cancer. Dose expansion studies are ongoing to further detect the safety and efficacy in these population. Clinical trial information: CTR20241120 .