Advanced Solid Tumors, Including Hepatocellular Carcinoma
Conditions
Interventions
In Part 1 (dose escalation), ZW251 will be administered intravenously once every 21 days (Q3W). Approximately 6 dose levels are expected as follows: Level 1: 3.2 mg/kg, Level 2: 6.4 mg/kg, Level 3: 9.
Sponsors
Tsutsui Toshio
Eligibility
Sex/Gender
All
Inclusion criteria
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 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 Adequate organ function
Exclusion criteria
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. Portal vein thrombosis within 3 months prior to Cycle 1 Day 1 that require coagulation therapy or is not stable. Known gastrointestinal bleeding within 3 months. Acute or chronic uncontrolled renal disease, pancreatitis, or non-malignant liver disease.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of dose-limiting toxicities (DLTs; Part 1) [Time Frame: 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) [Time Frame: Up to approximately 2 years] -Number of participants who experienced AEs, adverse events of special interest, or serious adverse events Incidence of clinical laboratory abnormalities (Parts 1 and 2) [Time Frame: 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 Confirmed objective response rate (Part 2) [Time Frame: 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 |
|---|---|
| Confirmed objective response rate (Part 1) [Time Frame: 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) [Time Frame: Up to approximately 2 years] Disease control rate (Parts 1 and 2) [Time Frame: 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 Duration of response (Parts 1 and 2) [Time Frame: 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 (Parts 1 and 2) [Time Frame: 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 Overall survival (Part 2) [Time Frame: Up to approximately 2 years] -The time from the date of the first dose of study treatment to the date of death due to any cause Area under the concentration-time curve (AUC0-504) of ZW251 (Parts 1 and 2) [Time Frame: 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) [Time Frame: Up to approximately 2 years] -ZW251 maximum concentration after first dose administration Area under the concentration-time curve of ZW251 at steady state (AUCtau,ss; Parts 1 and 2) [Time Frame: 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 (Cmax, ss; Parts 1 and 2) [Time Frame: Up to approximately 2 years] -ZW251 maximum concentration at steady state after fourth dose ad | — |
Countries
Ireland, Japan, Portugal, Spain, Taiwan, United States
Contacts
Public ContactToshio Tsutsui
PPD-SNBL K. K.
Outcome results
None listed