Zanidatamab Shows Promise in Extending Survival for Advanced Biliary Tract Cancer
Published: 2026/01/11 07:19:11
Biliary tract cancer (BTC) is a rare and aggressive malignancy with a historically poor prognosis. Though, recent data from the HERIZON-BTC-01 trial (NCT04466891) are offering new hope for patients with HER2-positive advanced BTC. The trial demonstrates that zanidatamab, a novel bispecific antibody, can significantly prolong overall survival (OS) in this patient population, a particularly impactful finding given the typically fatal nature of the disease and a median OS of less than 13 months from diagnosis. These groundbreaking results were recently presented at the American Society of Clinical Oncology Gastrointestinal Cancers Symposium.
Zanidatamab Receives Global Approvals
Zanidatamab has already begun to change the treatment landscape for HER2-positive BTC, receiving accelerated approval from the U.S. Food and Drug Governance (FDA) in November 20241. Following this, the therapy has also gained conditional approval in both China2 and the European Union3, signaling its growing recognition as a valuable treatment option.
Understanding the HERIZON-BTC-01 Trial Design
The HERIZON-BTC-01 trial was a pivotal study designed to evaluate the efficacy of zanidatamab in patients with locally advanced, unresectable, or metastatic HER2-amplified BTC. Key eligibility criteria included confirmation of intra-hepatic cholangiocarcinoma (ICC) in 27% of patients, extra-hepatic cholangiocarcinoma (ECC) in 19%, and gallbladder cancer (GBC) in 53%. Participants were required to have progressed on prior gemcitabine-based chemotherapy and have a good performance status (ECOG PS of 1 or below), along with adequate organ and cardiac function.
Between September 15, 2020, and March 16, 2022, patients were enrolled and categorized into two cohorts based on immunohistochemistry (IHC) scores:
* Cohort 1: IHC 2+ or 3+ (indicating higher levels of HER2 protein expression)
* Cohort 2: IHC 0 or 1+ (indicating lower levels of HER2 protein expression)
Patients received intravenous zanidatamab at a dose of 20 mg/kg every two weeks. Tumor response was assessed after eight weeks, with landmark survival analyses conducted at week 9 and week 25 to evaluate long-term outcomes.
Significant Survival Benefits Demonstrated
The analysis of IHC3+ patients (N=27) revealed remarkable results. A substantial 88.9% (n=24) experienced a partial response (PR) by week 9, with the remaining 3 achieving a complete response (CR). Importantly, zanidatamab significantly improved median overall survival:
* Any-Responders: 24.5 months (95% CI, 16.6 months – not estimable [NE])
* Patients with Stable Disease (SD): 14.4 months (95% CI, 6.5-21.1)
* All Other Patients: 8.9 months (95% CI, 2.3-14.3)
This translates to a 60% reduction in the risk of disease progression or death for those who responded to treatment (HR, 0.40; 95% CI, 0.19-0.83) compared to patients with stable disease. Moreover, patients with stable disease experienced a 62% reduced risk compared to those with progressive disease (HR, 0.38; 95% CI, 0.17-0.82). patients who responded to zanidatamab saw a 70% reduction in death risk by week 9, increasing to 79% by week 25.
Subgroup Analysis Reveals Key Insights
Further analysis revealed interesting patterns in treatment response based on patient characteristics:
* Asian Patients: Demonstrated the highest rate of CR or PR (69%), but also the highest rate of progressive disease (62%).
* White Patients: Exhibited the highest rate of stable disease (50%).
* ECOG Performance Status: Patients with an ECOG PS of 1 showed higher rates of CR/PR (77% vs 23%) and SD (57% vs 43%) but also a higher rate of progressive disease (54% vs 46%) compared to those with an ECOG PS of 0.
* Cancer Type: Gallbladder cancer (GBC) cases had the highest rate of CR/PR (63%) but also the highest rate of PD (54%),while ICC showed the highest rate of SD (57%).
* disease Stage: patients diagnosed with stage IV disease had the highest rates of CR/PR (54%) and SD (50), but also the highest rate of PD (62%).
These findings suggest that while zanidatamab demonstrates broad efficacy, response rates can vary based on individual patient characteristics.
Continued Research and future Directions
The authors of the HERIZON-BTC-01 trial concluded that objective response or stable disease with zanidatamab is associated with longer overall survival in BTC. They also highlighted the potential clinical benefit for patients who achieve early stable disease, suggesting continued treatment with zanidatamab may be warranted.
Currently, a phase 3 trial, HERIZON-BTC-302 (NCT06282575), is underway to evaluate the combination of zanidatamab with standard-of-care chemotherapy as a first-line treatment for HER2-positive BTC. This ongoing research promises to further refine treatment strategies and potentially improve outcomes for patients facing this challenging cancer.
Key Takeaways
* Zanidatamab demonstrates significant potential in prolonging overall survival for patients with HER2-positive advanced biliary tract cancer.
* The HERIZON-BTC-01 trial provides compelling evidence of zanidatamab’s efficacy, leading to accelerated and conditional approvals in multiple regions.
* Patient characteristics, such as race, performance status, cancer type, and disease stage, can influence treatment response.
* Ongoing research, including the HERIZON-BTC-302 trial, aims to optimize treatment strategies and further improve outcomes for patients with BTC.
References:
- Harding JJ, Fan J, Oh DY, et al. Landmark analysis of overall survival (OS) by objective response in patients (pts) with previously treated, advanced HER2-positive biliary tract cancer (BTC): post hoc analysis of the HERIZON-BTC-01 trial. Presented at: American Society of Clinical Oncology Gastrointestinal Cancers Symposium; January 8-10, 2026; San Francisco, CA. Abstract 545.
- Santoro C. FDA approves zanidatamab-hrii for HER2+ biliary tract cancer. AJMC. November 21, 2024.Accessed January 9,2026. https://www.ajmc.com/view/fda-approves-zanidatamab-hrii-for-her2-biliary-tract-cancer
- zymeworks announces NMPA approval of zanidatamab in China for adults with previously treated, unresectable or metastatic HER2-high expression (IHC3+) biliary tract cancer. News release. zymeworks. May 30, 2025. Accessed January 9, 2026. https://ir.zymeworks.com/news-releases/news-release-details/zymeworks-announces-nmpa-approval-zanidatamab-china-adults
- Doherty K. Zanidatamab nets European approval in pretreated HER2+ biliary tract cancer. OncLive.July 1, 2025. Accessed January 9, 2026. https://www.onclive.com/view/zanidatamab-nets-european-approval-in-pretreated-her2-biliary-tract-cancer
- A study of ZW25 (zanidatamab) in subjects with advanced or metastatic HER2-amplified biliary tract cancers (HERIZON-BTC-01). ClinicalTrials.gov. Updated September 15, 2025. Accessed January 9, 2026. https://clinicaltrials.gov/study/NCT04466891
