Mesothelin-expressing Advanced Cancers
Conditions
Keywords
Advanced or Metastatic Cancers, ADC, Antibody drug conjugate
Brief summary
This study is being done to find out if ZW171 is safe and can treat participants with advanced (locally advanced \[inoperable\] and/or metastatic) mesothelin-expressing cancers.
Detailed description
Part 1 of the study will evaluate the safety and tolerability of ZW171. Part 2 of the study will evaluate the anti-tumor activity of ZW171 while continuing to evaluate the safety and tolerability.
Interventions
DRUGZW171
Administered per protocol requirements
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 confirmed diagnosis of cancers with evidence of locally advanced (unresectable) and/or metastatic disease. Cancers that are refractory to all available standard of care (SOC) treatment, cancers for which no SOC treatment is available, or the participant cannot tolerate or refuses SOC therapy. * An Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1. * Adequate cardiac left ventricular function, as defined by left ventricular ejection fraction ≥ 50% as determined by either echocardiogram or multigated acquisition scan. * Adequate organ function.
Exclusion criteria
* Known additional malignancy that is progressing or that has required active treatment. * Undergone prior allogenic tissue (e.g., hematopoietic stem cell) or solid organ transplantation within the last 5 years. * Ongoing, clinically significant toxicity (Grade ≥ 2) associated with prior cancer therapies, with the exception of alopecia. * Advanced/metastatic, symptomatic, visceral spread, at risk of life-threatening complications in the short-term (including participants with massive uncontrolled effusion \[pleural, pericardial\], pulmonary lymphangitis, active unresolved bowel obstruction, massive ascites \[requiring paracentesis \>2 times within 2 weeks prior to the first dose\], and over 50% liver involvement). * Acute or chronic uncontrolled renal disease, pancreatitis, or liver disease (with exception of participants with Gilbert's Syndrome, asymptomatic gall stones, liver metastases, or stable chronic liver disease per investigator assessment). * Active or recurrent clinically significant autoimmune disease requiring systemic high-dose corticosteroids or immunosuppressive drugs.
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 ZW171 |
| Incidence of adverse events (AEs; Parts 1 and 2) | Up to approximately 2 years | Number of participants who experienced AEs or serious adverse events (SAEs) |
| Incidence of cytokine release syndrome (CRS; Parts 1 and 2) | Up to approximately 2 years | Number of participants who experienced CRS |
| Incidence of neurotoxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS; Parts 1 and 2) | Up to approximately 2 years | Number of participants who experienced neurotoxicity, including ICANS |
| 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 |
| Incidence of anti-drug antibodies (ADAs; Parts 1 and 2) | Up to approximately 7 months | Number of participants who develop ADAs |
| 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 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 |
| Progression-free survival (PFS), including 1-year 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 |
| 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 stable disease (SD) during treatment per RECIST v1.1 |
| Overall survival (OS), including 1-year OS (Part 2) | Up to approximately 2 years | The time from the first dose of ZW171 until the date of death from any cause |
| Serum concentration of ZW171 (Parts 1 and 2) | Up to approximately 7 months | Maximum serum concentration and trough concentration of ZW171 |
Countries
Germany, South Korea, United Kingdom, United States
Outcome results
None listed