Description:
This study is being done to find out if zanidatamab when given with ALX148 is safe and can
treat patients with advanced (locally advanced [inoperable] and/or metastatic) human
epidermal growth factor receptor 2 (HER2)-expressing cancer.
Title
- Brief Title: A Study of Zanidatamab (ZW25) With ALX148 in Patients With Advanced HER2-expressing Cancer
- Official Title: A Phase 1b/2, 2-part Open-label Study to Assess the Safety and Antitumor Activity of Zanidatamab in Combination With ALX148 in Advanced HER2-expressing Cancer
Clinical Trial IDs
- ORG STUDY ID:
ZWI-ZW25-204
- NCT ID:
NCT05027139
Conditions
Interventions
Drug | Synonyms | Arms |
---|
Zanidatamab | ZW25 | Zanidatamab plus ALX148 |
ALX148 | | Zanidatamab plus ALX148 |
Purpose
This study is being done to find out if zanidatamab when given with ALX148 is safe and can
treat patients with advanced (locally advanced [inoperable] and/or metastatic) human
epidermal growth factor receptor 2 (HER2)-expressing cancer.
Detailed Description
Part 1 of the study will first evaluate the safety and tolerability and establish the
recommended doses (RDs) of zanidatamab in combination with ALX148. Part 2 of the study will
evaluate the anti-tumor activity of the combination of zanidatamab plus ALX148 at the RD
levels in indication-specific expansion cohorts.
Trial Arms
Name | Type | Description | Interventions |
---|
Zanidatamab plus ALX148 | Experimental | | |
Eligibility Criteria
Inclusion Criteria:
- Locally advanced (inoperable) and/or metastatic HER2-expressing cancer as follows:
- Parts 1 and 2: HER2-positive breast cancer as defined per American Society of
Clinical Oncology (ASCO)/ College of American Pathologists (CAP) guidelines
- Parts 1 and 2: HER2-low breast cancer (defined as immunohistochemistry [IHC] 1+
or IHC 2+; AND is not HER2-positive per the ASCO/CAP guidelines)
- Part 2: HER2-positive gastroesophageal adenocarcinoma as defined per the ASCO/CAP
gastric cancer-specific guidelines; other HER2-overexpressing non-breast cancers
(defined as IHC 3+; or IHC 2+ and in situ hybridization [ISH]+) per the ASCO/CAP
guidelines for breast cancer
- Progression after or during the most recent systemic regimen of treatment for advanced
cancer. For both Part 1 and Part 2, prior therapies must have included approved agents
known to confer clinical benefit.
- Subjects with HER2-positive breast cancer who did not receive trastuzumab or
pertuzumab due to medical contraindications will not be eligible for this study
- Subjects with HER2-low breast cancer who have received prior HER2-targeted
therapy will not be eligible for this study
- Measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1
(RECIST 1.1)
- Confirmed HER2 protein expression and gene amplification by IHC and ISH assays,
respectively, at a central laboratory on new biopsy tissue
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Adequate organ functions
- Adequate cardiac left ventricular function, as defined by a left ventricular ejection
fraction (LVEF) ≥ 50% as determined by either echocardiogram or multiple gated
acquisition scan (MUGA) obtained within 4 weeks prior to first dose of study treatment
Exclusion Criteria:
- Previous allogeneic stem cell transplant
- Prior treatment with any anti-CD47 or anti-signal regulatory protein alpha (SIRPα)
agent
- Prior or concurrent invasive malignancy whose natural history or treatment has, in the
opinion of the investigator or medical monitor, the potential to interfere with the
safety or efficacy assessment of the investigational regimen
- Received systemic anticancer therapy within 4 weeks of starting study treatment (6
weeks for mitomycin C or nitrosoureas). Received radiotherapy within 2 weeks of the
first dose of zanidatamab/ALX148
- Untreated brain metastases, symptomatic brain metastases, or radiation treatment for
brain metastases within 4 weeks of start of study treatment
- Known leptomeningeal disease
- Active hepatitis
- Infection with human immunodeficiency virus (HIV)-1 or HIV-2. (Exception: Subjects
with well controlled HIV [e.g., CD4 > 350/mm3 and undetectable viral load] are
eligible.)
- QTc Fridericia (QTcF) > 470 ms
- History of myocardial infarction or unstable angina within 6 months prior to
enrollment, troponin levels consistent with myocardial infarction, or clinically
significant cardiac disease, such as ventricular arrhythmia requiring therapy,
uncontrolled hypertension, or any history of symptomatic congestive heart failure
- Acute or chronic uncontrolled pancreatitis or Child-Pugh Class C liver disease
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Incidence of dose-limiting toxicities (DLTs; Part 1) |
Time Frame: | Up to 4 weeks |
Safety Issue: | |
Description: | Number of patients who experienced a DLT. DLTs include specifically defined adverse events (AEs) considered to be related to zanidatamab or ALX148, including combination of zanidatamab with ALX148 |
Secondary Outcome Measures
Measure: | Disease control rate (DCR)(Part 2) |
Time Frame: | Up to 2 years |
Safety Issue: | |
Description: | Number of patients who achieved a best response of CR, PR, or stable disease (SD) during treatment per RECIST 1.1 |
Measure: | Clinical benefit rate (CBR)(Part 2) |
Time Frame: | Up to 2 years |
Safety Issue: | |
Description: | Number of patients who achieved a SD for ≥ 24 weeks or a confirmed BOR of CR or PR during treatment per RECIST 1.1 |
Measure: | Duration of response (DOR)(Part 2) |
Time Frame: | Up to 2 years |
Safety Issue: | |
Description: | 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 ALX148) from any cause |
Measure: | Progression-free survival (PFS)(Part 2) |
Time Frame: | Up to 2 years |
Safety Issue: | |
Description: | 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 |
Measure: | Progression-free survival 6 (PFS6)(Part 2) |
Time Frame: | Up to 6 months |
Safety Issue: | |
Description: | Number of patients with a PFS time ≥ 24 weeks |
Measure: | Overall survival (OS)(Part 2) |
Time Frame: | Up to 2 years |
Safety Issue: | |
Description: | The time from first dose of study treatment until death from any cause |
Measure: | Incidence of AEs (Part 2) |
Time Frame: | Up to 7 months |
Safety Issue: | |
Description: | Number of patients who experienced AEs, SAEs, or AESIs |
Measure: | Incidence of clinical laboratory abnormalities (Part 2) |
Time Frame: | Up to 7 months |
Safety Issue: | |
Description: | 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 |
Measure: | Maximum serum concentration of zanidatamab and ALX148 (Part 2) |
Time Frame: | Up to 7 months |
Safety Issue: | |
Description: | |
Measure: | Trough concentration of zanidatamab and ALX148 (Part 2) |
Time Frame: | Up to 7 months |
Safety Issue: | |
Description: | Minimum observed serum concentration (trough) |
Measure: | Incidence of anti-drug antibodies (ADAs)(Part 2) |
Time Frame: | Up to 7 months |
Safety Issue: | |
Description: | Number of patients who develop ADAs |
Details
Phase: | Phase 1/Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Zymeworks Inc. |
Last Updated
August 30, 2021