Results From HERIZON-BTC-01: Zanidatamab in Previously Treated HER2-Amplified BTC

September 2023, Vol 4, No 3

Improving clinical outcomes in the second line of treatment in patients with advanced biliary tract cancer (BTC) remains an important goal, and researchers have been exploring different therapeutic targets, including HER2, a protein that encourages cell growth and accelerates the spread of cancers.1-3 HER2-targeted therapies have demonstrated clinical benefit in patients with breast, lung, and gastric cancers, but there is currently no approved HER2-targeted therapy for patients with BTC.2 Zanidatamab is a HER2-targeted bispecific antibody that has demonstrated promising activity in a phase 1 trial, which included patients with BTC.4 At the ASCO 2023 meeting, Shubham Pant, MD, MBBS, presented preliminary results from the phase 2b HERIZON-BTC-01 study, which is investigating the efficacy of zanidatamab in patients with HER2-positive BTC.2

This ongoing study launched in September of 2020 and has since completed recruitment. The primary end point was confirmed objective response rate (cORR), and select secondary end points included duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival, and safety.2 A total of 87 patients were placed in either cohort 1 or cohort 2 depending on their immunohistochemistry (IHC) test score: 80 patients were placed in cohort 1 (IHC 2+ or 3+) and 7 patients in cohort 2 (IHC 0 or 1+). In cohort 1, 41 patients had gall bladder cancer, 23 patients had intrahepatic cholangiocarcinoma, and 16 patients had extrahepatic cholangiocarcinoma. Results from cohort 2 were not included as it contained a small sample size and did not reveal any unique responses.2

The cORR of patients in cohort 1 was 41.3%, confirmed by both independent central review and investigator assessment.2 In addition, in cohort 1, the DCR was 68.8%, and 68.4% of evaluable patients had a decrease in target lesions.2 The median PFS was 5.5 months in cohort 1, and overall survival data are not yet available.2 The median duration of treatment was 5.6 months, median DOR was 12.9 months, and median time to first response was 1.8 months.2 The most common treatment-related adverse events (TRAEs) of any grade in both cohorts included diarrhea (n=36), infusion-related reactions (n=30), decrease in ejection fraction (n=11), nausea (n=9), and anemia (n=6).2 Only 2 patients experienced TRAEs leading to treatment discontinuation (grade 2 decrease in ejection fraction and grade 3 pneumonitis).2 No treatment-related deaths occurred.2

Shubham Pant, MD, MBBS

Zanidatamab demonstrated antitumor activity in patients with treatment-refractory HER2-positive BTC while exhibiting a manageable and tolerable safety profile. From these preliminary data, Dr Pant concluded that zanidatamab may provide clinical benefit and has the potential to become a treatment option in patients with HER2-positive BTC.2


  1. Valle JW, Kelley RK, Nervi B, Oh DY, Zhu AX. Biliary tract cancer. Lancet. 2021;397(10272):428-444.
  2. Pant S, Fan J, Oh D-Y, et al. Results from the pivotal phase2b HERIZON-BTC-01 study: zanidatamab in previously-treated HER2-amplified biliary tract cancer (BTC). Presented at: ASCO 2023 Annual Meeting, June 2-6; Chicago, IL.
  3. Connell CM, Doherty GJ. Activating HER2 mutations as emerging targets in multiple solid cancers. ESMO Open. 2017;2(5):e000279.
  4. Meric-Bernstam F, Beeram M, Hamilton E, et al. Zanidatamab, a novel bispecific antibody, for the treatment of locally advanced or metastatic HER2-expressing or HER2-amplified cancers: a phase 1, dose-escalation and expansion study. Lancet Oncol. 2022;23(12):1558-1570.

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