This is a multicenter, global, Phase 2, open-label, 2-part, first-line study to investigate the safety, tolerability, and anti-tumor 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).
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-tumor activity of ZW25 plus combination chemotherapy in HER2-expressing GEA, BTC, and CRC.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
74
* Part 1: administered IV at dose levels and schedules determined by the Safety Monitoring Committee (SMC) * Part 2: RD identified in Part 1
Administered orally twice daily (PO bid)
Administered IV
Administered IV
Administered IV
Administered IV
Administered IV
Administered IV
USC/Norris Comprehensive Cancer Center
Los Angeles, California, United States
Hoag Memorial Hospital Presbyterian
Newport Beach, California, United States
H. Lee Moffitt Cancer Center
Tampa, Florida, United States
University of Chicago
Chicago, Illinois, United States
The Cancer and Hematology Centers
Grand Rapids, Michigan, United States
Nebraska Methodist Hospital
Omaha, Nebraska, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States
Sarah Cannon Research Institute
Nashville, Tennessee, United States
MD Anderson Cancer Center
Houston, Texas, United States
...and 13 more locations
Incidence of dose-limiting toxicities (DLTs) (Part 1)
Number of participants who experienced a DLT. DLTs include adverse events considered to be related to study treatment, including the evaluated dose level of ZW25, any component or combination of the components of a chemotherapy regimen, or the combination of ZW25 plus a chemotherapy regimen.
Time frame: Up to 6 weeks
Incidence of adverse events (Part 1)
Number of participants who experienced an adverse event
Time frame: Up to 11 months
Incidence of lab abnormalities (Part 1)
Number of participants who experienced a maximum severity of Grade 3 or higher post-baseline laboratory abnormality, including either hematology and chemistry. Grades are defined using National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.
Time frame: Up to 11 months
Objective response rate (ORR) (Part 2)
Number of participants who achieved a best response of either complete response (CR) or partial response (PR) during treatment according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Time frame: Up to 10 months
Objective response rate (ORR) (Part 1)
Number of participants who achieved a best response of either CR or PR during treatment per RECIST 1.1
Time frame: Up to 10 months
Disease control rate (Parts 1 and 2)
Number of participants who achieved a best response of CR, PR, or stable disease (SD) during treatment per RECIST 1.1
Time frame: Up to 10 months
Duration of response (Parts 1 and 2)
Median duration of response (in months) and range (minimum, maximum)
Time frame: Up to 2 years
Clinical benefit rate (Parts 1 and 2)
Number of participants with SD for ≥ 24 weeks or a confirmed, best overall response of CR or PR per RECIST 1.1
Time frame: Up to 2 years
Progression-free survival (Parts 1 and 2)
Median progression-free survival (in months) and range (minimum, maximum)
Time frame: Up to 2 years
Overall survival (Parts 1 and 2)
Median overall survival (in months) and range (minimum, maximum)
Time frame: Up to 2 years
Incidence of anti-drug antibodies (ADAs) (Parts 1 and 2)
Number of participants who develop ADAs
Time frame: Up to 11 months
End of infusion concentration of ZW25 (Parts 1 and 2)
Time frame: Up to 11 months
Maximum serum concentration of ZW25 (Parts 1 and 2)
Time frame: Up to 11 months
Trough concentration of ZW25 (Parts 1 and 2)
Time frame: Up to 11 months
Incidence of adverse events (Part 2)
Number of participants who experienced an adverse event
Time frame: Up to 11 months
Incidence of lab abnormalities (Part 2)
Number of participants who experienced a maximum severity of Grade 3 or higher post-baseline laboratory abnormality, including either hematology and chemistry. Grades are defined using National Cancer Institute's CTCAE, version 5.0.
Time frame: Up to 11 months
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