A Safety and Efficacy Study of ZW25 (Zanidatamab) Plus Combination Chemotherapy in HER2-expressing Gastrointestinal Cancers, Including Gastroesophageal Adenocarcinoma, Biliary Tract Cancer, and Colorectal Cancer

Official Title

Phase 2 Study of ZW25 Plus First-line Combination Chemotherapy in HER2-Expressing Gastrointestinal (GI) Cancers, Including Gastroesophageal Adenocarcinoma (GEA), Biliary Tract Cancer (BTC), and Colorectal Cancer (CRC)

Summary:

This is a multicentre, global, Phase 2, open-label, 2-part, first-line study to investigate the safety, tolerability, and anti-tumour activity of ZW25 (zanidatamab) plus standard first-line combination chemotherapy regimens for selected gastrointestinal (GI) cancers. Eligible patients include those with unresectable, locally advanced, recurrent or metastatic HER2-expressing gastroesophageal adenocarcinoma (GEA), biliary tract cancer (BTC), or colorectal cancer (CRC).

Trial Description

Primary Outcome:

• Incidence of dose-limiting toxicities (DLTs) (Part 1)
• Incidence of adverse events (Part 1)
• Incidence of lab abnormalities (Part 1)
• Objective response rate (ORR) (Part 2)

Secondary Outcome:

• Objective response rate (ORR) (Part 1)
• Disease control rate (Parts 1 and 2)
• Duration of response (Parts 1 and 2)
• Clinical benefit rate (Parts 1 and 2)
• Progression-free survival (Parts 1 and 2)
• Overall survival (Parts 1 and 2)
• Incidence of anti-drug antibodies (ADAs) (Parts 1 and 2)
• End of infusion concentration of ZW25 (Parts 1 and 2)
• Maximum serum concentration of ZW25 (Parts 1 and 2)
• Trough concentration of ZW25 (Parts 1 and 2)
• Incidence of adverse events (Part 2)
• Incidence of lab abnormalities (Part 2)

Part 1 of the study will first evaluate the safety and tolerability of ZW25 plus standard first-line combination chemotherapy (XELOX, FP, or mFOLFOX6 for GEA; mFOLFOX6 with or without bevacizumab for CRC; and CisGem for BTC) 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-tumour activity of ZW25 plus combination chemotherapy in HER2-expressing GEA, BTC, and CRC.

View this trial on ClinicalTrials.gov