Overall Survival and Longer Follow-Up From the Phase 2b HERIZON-BTC-01 Study: Zanidatamab in Patients With Previously Treated HER2-Positive Biliary Tract Cancer

Patients diagnosed with biliary tract cancer (BTC) that has progressed following initial treatment have a grim prognosis, typically surviving for a median of 6 to 9 months with subsequent chemotherapy. Zanidatamab, an HER2-targeted bispecific antibody, has shown promising antitumor effects in the phase 2b HERIZON-BTC-01 trial, with a previously reported confirmed objective response rate (cORR) of 41.3% and manageable safety outcomes in patients with previously treated HER2-positive BTC. An updated analysis, including overall survival (OS), was presented at ASCO 2024.

HERIZON-BTC-01 (NCT04466891), the ongoing open-label, global, phase 2b trial, is evaluating zanidatamab (20 mg/kg intravenously every 2 weeks) in patients with locally advanced, unresectable, or metastatic BTC (gallbladder cancer, intra/extrahepatic cholangiocarcinoma) and HER2/ERBB2 gene amplification and immunohistochemistry 2+ or 3+ (cohort 1; HER2-positive), or 0 or 1+ (cohort 2). Patients were previously treated with gemcitabine-containing regimens. The primary end point is cORR, with secondary end points including duration of response (DOR), OS, progression-free survival (PFS), and the frequency and severity of adverse events (AEs). Efficacy analyses have been updated for cohort 1 only, while safety analyses encompass both cohorts 1 and 2.

As of the data cutoff on July 28, 2023, the median follow-up period was 21.9 months. Among the 80 patients in cohort 1 (HER2-positive), treatment was still ongoing for 9 (11%) patients, and 11 (14%) patients were in survival follow-up. The cORR remained the same as in the primary analysis, with 33 (41.3%) patients showing a response, including 1 additional complete response (n=2; 2.5%). The median DOR increased by approximately 2 months to 14.9 months (95% confidence interval [CI], 7.4-not reached). The median PFS was maintained at 5.5 months (95% CI, 3.6-7.3). The median OS was 15.5 months (95% CI, 10.4-18.5), with a 12-month OS rate of 56.2% (95% CI, 44.3-66.5). Of the 87 patients in cohorts 1 and 2, 18 (20.7%) patients experienced grade ≥3 treatment-related adverse events (TRAEs). The most common grade 3 TRAEs (occurring in >2 patients) were diarrhea (4 [4.6%]), anemia (3 [3.4%]), and decreased ejection fraction (3 [3.4%]). Only 1 patient had a grade 4 TRAE (increased aspartate aminotransferase). There were no deaths related to zanidatamab treatment. Serious AEs occurred in 8 (9.2%) patients; 2 (2.3%) patients discontinued treatment due to an AE.

Zanidatamab showed a median OS of 15.5 months and a median DOR of 14.9 months in patients with HER2-positive BTC who had been previously treated. This represents an increase from the initial report and addresses the significant unmet need in this patient population. Safety remained manageable with additional follow-up, and there is an ongoing phase 3 trial of zanidatamab in combination with standard-of-care therapy in the first-line setting for patients with HER2-positive BTC.

Source:

Pant S, Fan J, Oh DY, et al. Zanidatamab in previously-treated HER2-positive (HER2+) biliary tract cancer (BTC): overall survival (OS) and longer follow-up from the phase 2b HERIZON-BTC-01 study. Chicago, IL & online: presented at 2024 ASCO Annual Meeting; abstract 4091.