This study is being done to find out if zanidatamab when given with evorpacept (ALX148) is safe and can treat patients with advanced (locally advanced \[inoperable\] and/or metastatic) human epidermal growth factor receptor 2 (HER2)-expressing cancer.
Part 1 of the study will first evaluate the safety and tolerability and establish the recommended doses (RDs) of zanidatamab in combination with evorpacept (ALX148). Part 2 of the study will evaluate the anti-tumor activity of the combination of zanidatamab plus evorpacept (ALX148) at the RD levels in indication-specific expansion cohorts.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
52
Administered intravenously (IV)
Administered IV
UC San Diego - Moores Cancer Center
La Jolla, California, United States
UCLA Department of Medicine Hematology/Oncology
Los Angeles, California, United States
UC Irvine Health - Chao Family Comprehensive Cancer Center
Orange, California, United States
Incidence of dose-limiting toxicities (DLTs; Part 1)
Number of patients who experienced a DLT. DLTs include specifically defined adverse events (AEs) considered to be related to zanidatamab or evorpacept (ALX148), including combination of zanidatamab with evorpacept (ALX148)
Time frame: Up to 4 weeks
Incidence of AEs (Part 1)
Number of patients who experienced AEs, serious adverse events (SAEs), or adverse events of special interest (AESIs)
Time frame: Up to 7 months
Incidence of clinical laboratory abnormalities (Part 1)
Number of patients who experienced a Grade 3 or higher post-baseline laboratory abnormality, including either hematology or chemistry. Grades are defined using National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0
Time frame: Up to 7 months
Confirmed objective response rate (ORR)(Part 2)
Number of patients who achieved a confirmed best overall response (BOR) of either complete response (CR) or partial response (PR) during treatment per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Time frame: Up to 2 years
Disease control rate (DCR)(Part 2)
Number of patients who achieved a best response of CR, PR, or stable disease (SD) during treatment per RECIST 1.1
Time frame: Up to 2 years
Clinical benefit rate (CBR)(Part 2)
Number of patients who achieved a SD for ≥ 24 weeks or a confirmed BOR of CR or PR during treatment per RECIST 1.1
Time frame: Up to 2 years
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Florida Cancer Specialists
Sarasota, Florida, United States
Astera Cancer Care
East Brunswick, New Jersey, United States
University Hospitals Cleveland Medical Center
Cleveland, Ohio, United States
Magee-Womens Hospital of UPMC
Pittsburgh, Pennsylvania, United States
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States
University of Vermont Medical Center
Burlington, Vermont, United States
Northwest Medical Specialties, PLLC
Tacoma, Washington, United States
...and 1 more locations
Duration of response (DOR)(Part 2)
The time from the first objective response (CR or PR) to documented progressive disease per RECIST 1.1, clinical progression, or death within 30 days of last dose of study drug (zanidatamab and/or evorpacept \[ALX148\]) from any cause
Time frame: Up to 2 years
Progression-free survival (PFS)(Part 2)
The time from the first dose of study treatment to the date of documented disease progression (per RECIST 1.1), clinical progression, or death from any cause
Time frame: Up to 2 years
Progression-free survival 6 (PFS6)(Part 2)
Number of patients with a PFS time ≥ 24 weeks
Time frame: Up to 6 months
Overall survival (OS)(Part 2)
The time from first dose of study treatment until death from any cause
Time frame: Up to 2 years
Incidence of AEs (Part 2)
Number of patients who experienced AEs, SAEs, or AESIs
Time frame: Up to 7 months
Incidence of clinical laboratory abnormalities (Part 2)
Number of patients who experienced a maximum severity of Grade 3 or higher post-baseline laboratory abnormality, including either hematology or chemistry. Grades are defined using NCI-CTCAE, version 5.0
Time frame: Up to 7 months
Maximum serum concentration of zanidatamab and evorpacept (ALX148) (Part 2)
Time frame: Up to 7 months
Trough concentration of zanidatamab and evorpacept (ALX148) (Part 2)
Minimum observed serum concentration (trough)
Time frame: Up to 7 months
Incidence of anti-drug antibodies (ADAs)(Part 2)
Number of patients who develop ADAs
Time frame: Up to 7 months