China’s NMPA Accepts BLA for Zanidatamab in HER2+ Biliary Tract Cancer


Key Takeaways

  • Zanidatamab's BLA for HER2-positive biliary tract cancer accepted by China's NMPA, supported by phase 2b HERIZON-BTC-01 trial results.
  • HERIZON-BTC-01 trial showed a 41.3% ORR and a median DOR of 12.9 months for zanidatamab.
Gastric cancer | Image Credit: © Rasi -

Gastric/GEJ Cancer | Image Credit:
© Rasi -

The National Medical Products Administration (NMPA) in China has accepted the biologics license application (BLA) for zanidatamab for the second-line treatment of patients with HER2-positive biliary tract cancer.1

The application was supported by findings from the phase 2b HERIZON-BTC-01 (NCT04466891), which demonstrated that patients who received zanidatamab in cohort 1 (n = 80) achieved an objective response rate (ORR) of 41.3% (95% CI, 30.4%-52.8%) per independent central review, including 1 patient with a complete response. At the October 10, 2022, data cutoff the median duration of response (DOR) and progression-free survival (PFS) were 12.9 months (95% CI, 6.0-not estimable [NE]) and 5.5 months (95% CI, 3.7-7.2), respectively.1,2

“Acceptance of this BLA in China represents a significant milestone in the global effort to bring effective, targeted treatment options to those affected by locally advanced or metastatic HER2-positive biliary tract cancer,” Kenneth Galbraith, chair and chief executive officer of Zymeworks, stated in a press release.1 "We are grateful to all of the stakeholders who have worked tirelessly to help us reach this milestone, including our dedicated teams in manufacturing, quality control, regulatory affairs, and clinical research at Zymeworks, and our collaboration partner in Asia Pacific, BeiGene, as well as the study investigators, patients, and families who have supported this development program for zanidatamab. We remain confident about zanidatamab’s potential as a new treatment option for multiple HER2-expressing cancers, with ongoing phase 3 trials in first-line advanced or metastatic HER2-positive biliary tract cancer [HERIZON-BTC-302] and first-line HER2-positive gastroesophageal adenocarcinoma [HERIZON-GEA-01].”

In May 2024, the FDA granted priority review to a BLA seeking the approval of zanidatamab for the treatment of patients with previously treated, unresectable, HER2-positive, locally advanced or metastatic biliary tract cancer. The target action date under the Prescription Drug User Fee Act is November 29, 2024.3

HERIZON-BTC-01 was a global, multicenter, open-label study that examined the HER2-directed bispecific antibody zanidatamab in previously treated patients with unresectable, locally advanced, or metastatic HER2-positive biliary tract cancer. To be eligible for the trial, patients needed to be at least 18 years old; have pathologically confirmed, unresectable, locally advanced or metastatic, HER2-amplified gallbladder cancer, intrahepatic cholangiocarcinoma, or extrahepatic cholangiocarcinoma; or have previously received at least 1 gemcitabine-containing systemic chemotherapy regimen for unresectable, locally advanced or metastatic disease, or in the neoadjuvant or adjuvant setting with progression or recurrence within 6 months of completion. Patients were also required to have at least 1 measurable lesion per RECIST v1.1, adequate cardiac function, and an ECOG performance status of 0 or 1.2

Patients were enrolled onto prospectively defined cohorts according to HER2 immunohistochemistry (IHC) score. Cohort 1 included patients with a HER2 IHC of 2+ or 3+ (HER2-positive) and cohort 2 consisted of patients with a HER2 IHC of 0 or 1+ (HER2-negative and HER2-low). All patients received intravenous zanidatamab 20 mg/kg on days 1 and 15 of each 28-day cycle; zanidatamab treatment continued until disease progression, death, patient withdrawal, physician decision, or loss to follow-up.

The primary end point was confirmed ORR in cohort 1 per independent central review. Secondary end points included DOR, disease control rate, investigator-assessed ORR, and safety.

Although overall survival (OS) data were immature at the data cutoff, additional findings from HERIZON-BTC-01 showed that the 9-month OS rate was 69.9% (95% CI, 57.8%-79.1%) in cohort 1. In cohort 2, the median PFS and OS were 1.9 months (95% CI, 1.2-NE) and 5.5 months (95% CI, 1.2-10.1)

In the safety population (n = 87), most patients experienced a treatment-emergent adverse effect (TEAE; 97%). The most common grade 1 or 2 treatment-related adverse effects (TRAEs) that were reported in more than 10% of patients included diarrhea (32%), infusion-related reactions (33%), and decreased ejection fraction (6%). No grade 4 or 5 TRAEs were observed; 7 patients experienced serious TRAEs and 5 patients died within 30 days of receiving their last dose of zanidatamab.

“We further our mission by collaborating with other innovative companies to advance the development and delivery of impactful cancer medicines to more patients around the world,” Clare Fisher, senior vice president of business development at BeiGene, said in the press release.1 “We thank our partners at Zymeworks for their dedication and contributions toward achievement of this important milestone for zanidatamab. We look forward to continued partnership as we work to reach more patients in the Asia-Pacific region.”


  1. Zymeworks announces China NMPA acceptance of biologics license application for zanidatamab for second-line treatment of biliary tract cancer. News release. Zymeworks Inc. June 10, 2024. Accessed June 10, 2024.
  2. Harding JJ, Fan J, Oh DY, et al. Zanidatamab for HER2-amplified, unresectable, locally advanced or metastatic biliary tract cancer (HERIZON-BTC-01): a multicentre, single-arm, phase 2b study. Lancet Oncol. 2023;24(7):772-782. doi:10.1016/S1470-2045(23)00242-5
  3. Zanidatamab granted priority review for HER2-positive metastatic biliary tract cancer. News release. Jazz Pharmaceuticals. May 29, 2024. Accessed June 10, 2024.
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