Background: The HER2 bispecific antibody zani showed rapid, durable responses and a manageable safety profile in patients with HER2+ BTC in the pivotal HERIZON-BTC-01 study. Here we report pain outcomes and opioid use for patients in this trial. Methods: HERIZON-BTC-01 (NCT04466891), an ongoing, open-label, Phase 2b study, is assessing zani (20 mg/kg IV Q2W) in patients with HER2+ (gene amplification and immunohistochemistry 2+ or 3+ [Cohort 1] and 0 or 1+ [Cohort 2]), locally advanced, unresectable or metastatic BTC (gallbladder cancer, intra-/extra-hepatic cholangiocarcinoma) who received prior gemcitabine-containing treatment (tx). Exploratory endpoints assessed at baseline (BL) and every 8 weeks included the Brief Pain Inventory short form, the visual analog scale (VAS), and analgesic opioid use. Results: Of the 80 patients with HER2+ BTC in Cohort 1 who were assessed for primary efficacy (median age 64 yrs; 56% female), 1 (1%) had complete response (CR), 32 (40%) partial response (PR), 22 (28%) stable disease (SD), and 24 (30%) progressive disease (PD); 1 patient was not evaluable. Responders (CR or PR) generally reported improved pain scores and less pain interference with activities of daily living. Patients with PD generally had worsening pain scores and pain interference by time of best on tx score (BONT) (Table). Overall, patients who responded to zani reported improved quality of life (VAS scores) vs BL. Fewer patients with CR (0.0%; n=1) and PR (3.1%; n=32) increased opioid use overall post-BL vs patients with SD (9.1%; n=22) or PD (34.8%; n=23). Conclusions: Patients with HER2+ BTC who responded to zani reported less pain and pain interference compared with BL, further supporting the development of zani as a tx option for these patients, with the goal of improving patient outcomes. Clinical trial information: NCT04466891.

Change from BL for each patient is post-BL value minus BL value; negative values for change from BL indicate better outcomes and positive indicate worse.