A Safety and Efficacy Study of ZW25 Plus Combination Chemotherapy in HER2-expressing Gastroesophageal Adenocarcinoma
- Inclusion: - Disease diagnosis: - Part 1: Unresectable, locally advanced, recurrent or metastatic HER2-expressing GEA (IHC 3+ or 2+ with or without gene amplification based upon local assessment or central assessment) - Part 2: Unresectable, locally advanced, recurrent or metastatic HER2-high GEA (IHC 3+, or IHC 2+ and FISH+ by central review) - Tumor measurements as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1: - Part 1: Measurable or non-measurable disease - Part 2: Measurable disease - ECOG performance status score of 0 or 1 - Adequate organ function - Adequate cardiac left ventricular function, as defined by a LVEF >/= institutional standard of normal Exclusion: - Prior treatment with a HER2-targeted agent - Treatment with prior anti-cancer therapy, except prior adjuvant/neoadjuvant therapy, which must be completed at least 6 months prior to first study treatment dosing; and/or treatment with other cancer therapy, not otherwise specified in the exclusion criteria, within 4 weeks before the first dose of ZW25 - Untreated known brain metastases (patients with treated brain metastases who are off steroids and are stable for at least 1 month at the time of screening are eligible) - Having clinically significant cardiac disease or known myocardial infarction or unstable angina (within 6 months before first study treatment dosing) - QTc Fridericia (QTcF) > 450 ms - Peripheral neuropathy > Grade 1 per NCI-CTCAE v5.0 - Clinically significant interstitial lung disease - Prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen. - Active hepatitis B or hepatitis C infection or other known chronic liver disease or infection with Human Immunodeficiency Virus (HIV)-1 or HIV-2 (Exception: patients with well controlled HIV [e.g., CD4>350/mm3 and undetectable viral load] are eligible.)
Part 1 of the study will first evaluate the safety and tolerability of ZW25 plus physician's choice of first-line combination chemotherapy (XP, FP, mFOLFOX6, or XELOX) and will confirm the recommended dosage (RD) of ZW25 when administered in combination with each of these multi-agent chemotherapy regimens. Then, Part 2 of the study will evaluate the anti-tumor activity of ZW25 plus physician's choice of combination chemotherapy in HER2-high GEA.
Trial Phase Phase II
Trial Type Treatment
- Primary ID ZWI-ZW25-201
- Secondary IDs NCI-2019-03042
- Clinicaltrials.gov ID NCT03929666