Clinical News

A novel bispecific antibody zanidatamab elicits antitumor activity in HER2-amplified and overexpressing biliary tract cancers in a phase 2b clinical trial.


Abstract: Zanidatamab monotherapy demonstrated objective responses in HER2-amplified and overexpressed biliary tract cancers in the phase 2b HERIZON-BTC-01 trial.

Zanidatamab is a humanized bispecific HER2-HER2 antibody that directly targets the membrane-adjacent extracellular and dimerization domains of HER2. The mechanism of action of zanidatamab includes binding to different expression levels of HER2, receptor-antibody cluster formation, downregulation of HER2 through receptor internalization, and antibody-dependent cellular cytotoxicity. A tumor-agnostic phase 1 dose-escalation and expansion study published in The Lancet Oncology indicated that zanidatamab showed promising responses in these HER2-amplified solid tumors, such as biliary tract carcinoma (BTC), colorectal cancer (CRC) and other HER2-associated cancers in late-line settings.
This trial showed 38% response rate in both BTC and CRC; 62% and 77% in disease control rate respectively. The progression-free survival was 3.5 months and 6.8 months in BTC and CRC. Another phase 2b single-arm HERIZON-BTC-01 trial in BTC patients demonstrated the response of zanidatamab in these previously treated patients. Patients treated with zanidatamab achieved an ORR of 41.3%, with a median DoR of 12.9 months. Positive data from HERIZON-BTC-01 may support zanidatamab as a new alternative to chemotherapy in this treatment-refractory BTC patient with HER2 amplification.

Meric-Bernstam et al., Lancet Oncol 2022; 23: 1558–70

Zymeworks announces positive topline data in the pivotal HERIZON-BTC-01 trial of zanidatamab. News release. Zymeworks Inc. December 19, 2022. Accessed December 20, 2022.