Germ Cell Tumor, Hepatocellular Carcinoma, Squamous Cell Non-Small Cell Lung Cancer
Conditions
Keywords
GPC3-expressing cancer, hepatocellular carcinoma, antibody drug conjugate, ADC, Lung Cancer, Non-Small Cell Lung Cancer, Squamous Cell Cancer, Germ Cell Tumor
Brief summary
The purpose of this study is to find out if ZW251, an antibody-drug conjugate targeting glypican-3 (GPC3), is safe and can treat participants with advanced cancers, including hepatocellular carcinoma (HCC), squamous cell non-small cell lung cancer (NSCLC), or germ cell tumors (GCT).
Detailed description
Part 1 (dose escalation) of the study will evaluate the safety and tolerability of ZW251 in HCC, squamous cell NSCLC, and GCT. Part 2 (dose optimization) of the study will further assess safety and potential anti-tumor activity of the ZW251 established recommended doses in HCC.
Interventions
DRUGZW251
Administered intravenously
Sponsors
Zymeworks BC Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Pathologically or cytologically confirmed diagnosis of HCC with evidence of locally advanced (unresectable, and ineligible for transplant) and/or metastatic disease. Noninvasive methods may be used to confirm diagnosis * Pathologically or cytologically confirmed diagnosis of squamous cell NSCLC with evidence of locally advanced (unresectable) and/or metastatic disease * Pathologically or cytologically confirmed diagnosis of GCT with evidence of yolk sac and/or choriocarcinoma predominant component and locally advanced (unresectable) and/or metastatic disease * Measurable disease per RECIST v1.1 * Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1 * Liver function status of Child-Pugh Class A (for HCC only) * Adequate organ function
Exclusion criteria
* Known additional malignancy that is progressing or that has required active treatment within the last year * History of hepatic encephalopathy within the past 6 months or requirement for medications to control encephalopathy * Participants with HCC experiencing main portal vein tumor invasion require sponsor approval for enrollment * Known gastrointestinal bleeding within 3 months * Acute or chronic uncontrolled renal disease, pancreatitis, or non-malignant liver disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of dose-limiting toxicities (DLTs; Part 1) | Up to 3 weeks | Number of participants who experienced a DLT. DLTs include specifically defined adverse events (AEs) considered to be related to ZW251 |
| Incidence of AEs (Parts 1 and 2) | Up to approximately 2 years | Number of participants who experienced AEs, adverse events of special interest, or serious adverse events |
| Objective response rate (Part 2) | Up to approximately 2 years | Number of participants who achieved a best overall response of either confirmed complete response (CR) or partial response (PR) during treatment according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 |
| Incidence of clinical laboratory abnormalities (Parts 1 and 2) | Up to approximately 2 years | Number of participants who experienced a maximum severity of 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area under the concentration-time curve of ZW251 at steady state (AUCtau,ss; Parts 1 and 2) | Up to approximately 2 years | Area under the concentration-time curve of ZW251 at steady state after fourth dose administration |
| Maximum concentration of ZW251 at steady state (Сmax,ss; Parts 1 and 2) | Up to approximately 2 years | ZW251 maximum concentration at steady state after fourth dose administration |
| Minimal concentration of ZW251 at steady state (Сmin,ss; Parts 1 and 2) | Up to approximately 2 years | ZW251 minimal concentration at steady state after fourth dose administration |
| Duration of response (Parts 1 and 2) | Up to approximately 2 years | The time from the first objective response (CR or PR) to the first documented progressive disease (PD) per RECIST v1.1 or death within 30 days of last dose of study treatment from any cause. Only participants who achieve a confirmed response will be included in the analysis |
| Objective response rate (Part 1) | Up to approximately 2 years | Number of participants who achieved a best overall response of either confirmed CR or PR during treatment according to RECIST v1.1 |
| Best overall response (Parts 1 and 2) | Up to approximately 2 years | — |
| Disease control rate (Parts 1 and 2) | Up to approximately 2 years | Number of participants who achieved a best response of CR, PR, or stable disease during treatment per RECIST v1.1 |
| Incidence of anti-drug antibodies (ADAs; Parts 1 and 2) | Up to approximately 2 years | Number of participants who develop ADAs |
| Progression-free survival (Part 2) | Up to approximately 2 years | The time from the first dose of study treatment to the date of first documented PD per RECIST v1.1 or death from any cause |
| Area under the concentration-time curve (AUC0-504) of ZW251 (Parts 1 and 2) | Up to approximately 2 years | Area under the concentration-time curve of ZW251 after first dose administration |
| Maximum concentration (Cmax) of ZW251 (Parts 1 and 2) | Up to approximately 2 years | ZW251 maximum concentration after first dose administration |
Countries
Ireland, Japan, Portugal, Spain, Taiwan, United States
Contacts
CONTACTZymeworks Clinical Trial Resource
STUDY_DIRECTORMaggie Weinstein, MD, PhD, MPH
Zymeworks BC Inc.
Outcome results
None listed