Advanced Solid Tumors
Conditions
Keywords
Advanced or Metastatic Cancers, ADC, Folate alpha receptor
Brief summary
The purpose of this study is to find out if ZW191 is safe and can treat participants with advanced cancers, including ovarian, endometrial, and non-small cell lung cancers.
Detailed description
Part 1 of the study will evaluate the safety and tolerability of ZW191. Part 2 of the study will further evaluate safety and explore the potential anti-tumor activity of ZW191.
Interventions
DRUGZW191
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 cancers with evidence of locally advanced (unresectable), recurrent and/or metastatic disease. * Measurable disease per RECIST v1.1. * Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1. * Adequate cardiac function: Cardiac left ventricular function, as defined by left ventricular ejection fraction (LVEF) ≥ 50% as determined by either echocardiogram (ECHO) or multigated acquisition scan (MUGA). * Other adequate organ function.
Exclusion criteria
* Known additional malignancy that is progressing or requires active treatment or may interfere with study endpoints. * Has received prior Topoisomerase I inhibitor(TOPO1i) antibody drug conjugate treatment, regardless of washout period. * Acute or chronic uncontrolled renal disease, pancreatitis, or liver disease. * Severe chronic or active infections (including known active SARS-CoV-2 infection) requiring systemic therapy, including antibacterial, antifungal, or antiviral therapy.
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 ZW191 |
| Incidence of adverse events (AEs; Parts 1 and 2) | Up to approximately 2 years | Number of participants who experienced AEs, adverse events of special interest (AESIs), or serious adverse events (SAEs) |
| 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 (CTCAE), version 5.0 |
| Confirmed 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Confirmed 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 |
| Clinical benefit rate (Parts 1 and 2) | Up to approximately 2 years | Number of participants who achieved a best response of CR, PR, non-CR/non-progressive disease (PD), or stable disease (SD) lasting at least 180 days per RECIST v1.1 |
| Duration of response (DOR; Part 2) | Up to approximately 2 years | The time from the first objective response (CR or PR) to the first documented 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 |
| Disease control rate (DCR; Part 2) | Up to approximately 2 years | Number of participants who achieved a best response of CR, PR, non-CR/non-PD (for participants who have only non-target lesions), or SD during treatment per RECIST v1.1 |
| Progression-free survival (PFS; 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 |
| Best overall response (BOR; Part 2) | Up to approximately 2 years | — |
| Serum or plasma concentration and PK parameters of ZW191 (Parts 1 and 2) | Up to approximately 2 years | Maximum serum concentration and trough concentration of ZW191 |
| Incidence of anti-drug antibodies (ADAs; Parts 1 and 2) | Up to approximately 2 years | Number of participants who develop ADAs |
Countries
Australia, Japan, Singapore, South Korea, Spain, United States
Contacts
STUDY_DIRECTORMaggie Weinstein, MD, PhD, MPH
Zymeworks BC Inc.
Outcome results
None listed