Background: BB-1701 is an antibody-drug conjugate consisting of a humanized IgG1κ monoclonal antibody and eribulin. When BB-1701 targets HER2-expressing cancer cells and is internalized, free eribulin is cleaved from the ADC by cathepsin b and causes cytotoxicity to cancer cells. The neighboring cells were affected with bystander effects, like cytotoxicity on tumor cells and non-cytotoxic effects on microenvironment by free eribulin. Here, we report preliminary results from this phase 1 study (NCT04257110). Methods: This dose escalation study followed an accelerated titration and traditional "3 + 3" design with 6 dose levels from 0.4 to 2.6 mg/kg Q3W. Patients with confirmed advanced/metastatic HER2 overexpressing solid tumors, who had progressed on, or were intolerant to prior standard therapies, aged ≥ 18 years, with ECOG PS ≤ 2, and measurable disease, were enrolled. HER2 expressions were determined by IHC or next generation sequencing. Tumor imaging was conducted every 9 weeks. The primary objective is the assessment of safety and tolerability, and the secondary objective is the assessment of PK and preliminary anti-tumor activity. Results: A total of 29 patients were enrolled in this study. Tumor types were breast cancer, gastric/gastroesophageal junction cancer, colorectal cancer, gallbladder cancer, ovarian cancer and urothelial cancer. The medium prior lines of systemic therapy were 3 (range 1 – 6). During this study, no DLT was observed and the MTD was not reached. The most commonly reported (≥20%) treatment-related adverse events (TRAEs) were peripheral neuropathy, aspartate aminotransferase increased, neutrophil count decreased, white blood cell count decreased, alanine aminotransferase increased, hypertriglyceridemia, anemia, platelet count decreased. The most commonly reported ≥ grade 3 TRAEs (≥10 %) was peripheral neuropathy. There were two grade 4 adverse events: neurological symptom and sepsis. There was no interstitial lung disease observed during the study. Nine patients discontinued the study treatment due to peripheral neuropathy. Thirteen patients out of 26 patients evaluable for antitumor activity achieved partial response (PR), and 11 patients had stable diseases (SD). The best overall response rate (BOR) was 50.0% (13/26) and the disease control rate (DCR) was 92.3% (24/26). For 17 breast cancer patients in the study, 12 patients achieved PR, and 5 patients had SD. The BOR was 70.5% (12/17) and the DCR was 100% (17/17). For 5 gastric cancer patients in the study, all patients had SD. The duration of treatment ranged from 2 weeks to 66 weeks. Conclusions: BB-1701 was generally well tolerated up to 2.6 mg/kg dose levels and has shown promising antitumor activity in patients with HER2-overexpression solid tumors. Clinical trial information: NCT04257110.