Zanidatamab Wins Approval in China for Previously Treated, HER2+ Biliary Tract Cancer

HER2+ Biliary Tract Cancer

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China’s National Medical Products Administration (NMPA) has granted conditional approval to zanidatamab-hrii (Ziihera) for the treatment of patients with previously treated, unresectable or metastatic, HER2-positive (immunohistochemistry [IHC] 3+) biliary tract cancer.1

The continued approval of zanidatamab in this indication will depend on data from confirmatory clinical trials to verify the clinical benefit of the dual HER2-targeted bispecific antibody in this patient population.

“Zanidatamab’s conditional approval in China is a meaningful advancement for patients living with HER2-positive biliary tract cancer, a population with historically high unmet need and poor prognoses,” Kenneth Galbraith, chair and chief executive officer of Zymeworks, stated in a news release. “This milestone affirms the strength of zanidatamab’s clinical potential and reflects our continued focus on translating innovation into real impact for patients around the globe. We are deeply grateful to our partners at BeOne Medicines, and to the patients, families, and clinical teams whose contributions have made this milestone a reality. As Zymeworks continues to advance our broader development programs and R&D pipeline, we remain committed to realizing zanidatamab’s potential to transform the standard of care across HER2-expressing cancers.”

The conditional approval was based on findings from the phase 2b HERIZON-BTC-01 trial (NCT04466891), which also supported the November 2024 FDA accelerated approval of zanidatamab for the treatment of adult patients with previously treated, unresectable or metastatic HER2-positive (IHC 3+) biliary tract cancer, as detected by an FDA-approved test.1-3

Data supporting the FDA approval showed that in patients (n = 62) with unresectable or metastatic HER2-positive biliary tract cancer, all of whom received at least 1 prior gemcitabine-containing regimen in the advanced setting, zanidatamab elicited an objective response rate (ORR) of 52% (95% CI, 39%-65%) per independent central review and RECIST 1.1 criteria.2 The median duration of response (DOR) was 14.9 months (95% CI, 7.4-not estimable).

The multicenter, open-label, single-arm trial enrolled patients at least 18 years of age with histologically or cytologically confirmed, locally advanced or metastatic biliary tract cancer who were not eligible for curative resection, transplant, or ablative therapies.4 Prior treatment with at least 1 gemcitabine-containing regimen in the advanced setting was required, as was disease progression after or intolerance to the most recent line of therapy. In patients who received a perioperative gemcitabine-containing regimen, this counted as a line of therapy in the advanced setting if disease progression occurred less than 6 months from surgical resection or completion of adjuvant therapy.

Other key inclusion criteria comprised centrally confirmed HER2 amplification, an ECOG performance status of 0 or 1, and adequate organ and cardiac function.

Patients who had untreated central nervous system (CNS) metastases, those who had symptomatic CNS metastases, and patients who received radiation for CNS metastases within 4 weeks of start of study treatment were not allowed to enroll. Patients with stable, treated brain metastases are eligible if they were neurologically stable with no evidence of radiographic progression for at least 4 weeks at screening.

All patients received zanidatamab at 20 mg/kg once every 2 weeks.3

ORR was the trial’s primary end point.4 Secondary end points included DOR, disease control rate, progression-free survival, overall survival, and safety.

In the safety population (n = 80), serious adverse effects (AEs) were reported in 53% of patients. The most common AEs reported in at least 20% of patients included diarrhea, infusion-related reaction, abdominal pain, and fatigue.3 Serious AEs that occurred in more than 2% of patients included biliary obstruction (15%), biliary tract infection (8%), sepsis (8%), pneumonia (5%), diarrhea (3.8%), gastric obstruction (3.8%), and fatigue (2.5%).

One patient experienced a fatal AE (hepatic failure). AEs led to treatment discontinuation in 2.5% of patients.

The ongoing phase 3 trial HERIZON-BTC-302 trial (NCT06282575) is evaluating zanidatamab in combination with standard-of-care (SOC) therapy compared with SOC alone in the first-line setting for patients with HER2-positive biliary tract cancer.

References

1. 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 May 30, 2025. https://ir.zymeworks.com/news-releases/news-release-details/zymeworks-announces-nmpa-approval-zanidatamab-china-adults
2. FDA grants accelerated approval to zanidatamab-hrii for previously treated unresectable or metastatic HER2-positive biliary tract cancer. FDA. November 20, 2024. Accessed May 30, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-zanidatamab-hrii-previously-treated-unresectable-or-metastatic-her2
3. Jazz Pharmaceuticals announces U.S. FDA approval of Ziihera (zanidatamab-hrii) for the treatment of adults with previously treated, unresectable or metastatic HER2-positive (IHC 3+) biliary tract cancer (BTC). News release. Jazz Pharmaceuticals. November 20, 2024. Accessed May 30, 2025. https://investor.jazzpharma.com/news-releases/news-release-details/jazz-pharmaceuticals-announces-us-fda-approval-ziiherar
4. A study of ZW25 (zanidatamab) in subjects with advanced or metastatic HER2-amplified biliary tract cancers (HERIZON-BTC-01). ClinicalTrials.gov. Updated August 21, 2024. Accessed May 30, 2025. https://clinicaltrials.gov/study/NCT04466891