ZW25 in Subjects with Advanced or Metastatic HER2-Amplified Biliary Tract Cancer
Research type
Research Study
Full title
A Phase 2b, open-label, single-arm study of ZW25 monotherapy in subjects with advanced or metastatic HER2-amplified biliary tract cancers
IRAS ID
1003020
Contact name
Roopinder Gillmore
Contact email
Eudract number
2020-000459-11
Research summary
The proposed study is a multicentre, open-label, single-arm trial to evaluate the antitumour
activity of ZW25 monotherapy in subjects with HER2-amplified (Human
epidermal growth factor receptor 2), inoperable and advanced or metastatic biliary tract
cancer, including intra-hepatic cholangiocarcinoma, extra-hepatic cholangiocarcinoma,
and gallbladder cancer.
Biliary tract cancers poor prognosis cancers that account for approximately 3% of all
adult cancers. The outlook for patients with advance biliary tract cancer is very poor,
with an estimated 5-year survival rate of approximately 5 to 15% for all patients.
Current first line standard of care is Gemcitabine / Cisplatin (combination
chemotherapy) but if unsuccessful, other treatment options are is limited, and can cause
higher rate of adverse events and toxicities.
The objective of Zymeworks’ proposed study, ZWI-ZW25-203, is to evaluate the antitumour
activity of ZW25 single treatment in subjects with advanced or metastatic HER2-
amplified biliary tract cancers. HER2 is short for human epidermal growth factor
receptor 2. HER2 is a gene. Some cancers have extra copies of HER2 that can cause the
cancer cells to grow and form a tumour. This is known as HER2-expressing cancer.
ZW25 is a new, artificial antibody that binds to two different areas of the HER2 receptor.
This results in a block of pathways, growth and activation of antibody-dependent cellular
cytotoxicity.
Two cohorts of subjects will be enrolled:
• Cohort 1, comprising approximately 75 subjects with HER2 amplification by ISH and
HER2 overexpression by IHC; i.e., IHC 2+ or 3+
• Cohort 2, comprising approximately 25 subjects with HER2 amplification by ISH and
HER2 IHC 0 or 1+
Enrolled subjects will receive 20 mg/kg given intravenously of ZW25 every 2 weeks on
Days 1 and 15 of each 28-day cycle until treatment discontinuation.
Study procedures include, blood tests, CT / MRI, ECHO/MUGA, Physical examinations,
tumour biopsies.REC name
London - Hampstead Research Ethics Committee
REC reference
20/LO/0906
Date of REC Opinion
26 Aug 2020
REC opinion
Further Information Favourable Opinion