Carcinoma, Hepatocellular, Carcinoma, Non-Small-Cell Lung, Liver Neoplasms, Neoplasms
Conditions
Keywords
Glypican-3 (GPC3), GPC3-positive advanced solid tumors, AST-201, Aptamer-drug conjugate, Hepatocellular carcinoma (HCC), Advanced solid tumors, Metastatic, Dose Escalation and Expansion
Brief summary
This is the first in human trial clinical study of AST-201 in patients with GPC3-positive advanced solid tumors. This study aims to evaluate the safety, tolerability, pharmacokinetic properties, and preliminary efficacy of AST-201 across various tumor types.
Detailed description
AST-201 is a novel aptamer drug conjugate (ApDC) investigational agent with demonstrated preclinical efficacy in GPC3-positive tumor models. This Phase 1 clinical study aims to investigate the safety, tolerability, and preliminary efficacy of AST-201, targeting GPC3-positive advanced solid tumors. The study consists of two parts: Phase 1a and Phase 1b. In Phase 1a, AST-201 will be administered in a dose escalating manner across cohorts of patients to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D). In this dose-escalation phase, patients will receive AST-201 as a single agent, with safety, tolerability, and pharmacokinetic (PK) profiles assessed. In Phase 1b, patients will receive AST-201 at the RP2D across specific GPC3-positive tumor types to further explore safety and efficacy. This expansion phase focuses on assessing anti-tumor efficacy and overall safety in a broader patient population. Data collected from this study will support future clinical development of AST-201 in GPC3-positive advanced solid tumors.
Interventions
DRUGAST-201
AST-201 is administered intravenously on Days 1, 8, and 15 of each 28-day cycle, followed by a one-week rest period. Dosing is repeated until DLT or disease progression is occurred.
Sponsors
Aptamer Sciences, Inc.
CHA University
National Cancer Center, Korea
Samsung Medical Center
Severance Hospital
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male and female aged ≥19 years * Histologically and/or cytologically diagnosed as the advanced recurrent solid tumor * GPC3-positive confirmed by IHC test * At least 1 measurable or non-measurable but evaluable lesion as defined per RECIST v1.1 (modified RECIST for hepatocellular carcinoma) * ECOG performance status of 0 or 1 * Life expectancy at least 12 weeks * Adequate hematologic, hepatic, renal, and heart/coagulation function * Child-Pugh Class of A for HCC
Exclusion criteria
* Subjects with ischemic heart disease * Subjects with anti-tumor treatment within 4 weeks * Subjects with comorbidities such as uncontrolled hypertension, heart failure, etc. * Pregnant or potentially pregnant and lactating woman
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Limiting Toxicity (DLT) | 4 weeks | Dose-limiting toxicity (DLT) is defined as any treatment-related Grade 3 or higher adverse event, or other clinically significant toxicity occurring during the first cycle (4 weeks), that meets the protocol-defined criteria for dose limitation, based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version \[5.0\]. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Cmax | Cycle 1, Days 1-2 (cycle is 28 days) | Maximum Plasma Concentration (Cmax) |
| Pharmacokinetics (PK): Tmax | Cycle 1, Days 1-2 (cycle is 28 days) | Time to Reach Maximum Plasma Concentration (Tmax) |
| Pharmacokinetics (PK): AUC | Cycle 1, Days 1-2 (cycle is 28 days) | Area Under the Curve (AUC) |
| Pharmacokinetics (PK): Cl | Cycle 1, Days 1-2 (cycle is 28 days) | Clearance Rate |
| Pharmacokinetics (PK): t1/2 | Cycle 1, Days 1-2 (cycle is 28 days) | Half-Life (t1/2) |
| Objective Response Rate (ORR) | Baseline through the end of each 28-day cycle, up to 6 months. | Objective Response Rate (ORR) is defined as the proportion of subjects with the best overall response (BOR) assessed as complete response (CR) and partial response (PR). ORR assessed by the Investigator and evaluated according to RECIST 1.1 criteria. |
| Disease Control Rate (DCR) | Baseline through the end of each 28-day cycle, up to 6 months. | Disease Control Rate (DCR) is defined as the proportion of subjects with the BOR assessed as CR, PR, or stable disease (SD). DCR assessed by the Investigator and evaluated according to RECIST 1.1 criteria. |
| Duration of Response (DOR) | Baseline through the end of each 28-day cycle, up to 6 months. | Duration of Response (DOR) is defined as the period from the initial assessment date confirming CR or PR to disease progression (PD) or death. DOR assessed by the Investigator and evaluated according to RECIST 1.1 criteria. |
| Time to Progression (TTP) | Baseline through the end of each 28-day cycle, up to 6 months. | Time to Progression (TTP) is defined as the period from the initial administration of the investigational product (IP) to disease progression (PD). TTP assessed by the Investigator and evaluated according to RECIST 1.1 criteria. |
| Progression-Free Survival (PFS) | Baseline through the end of each 28-day cycle, up to 6 months. | Progression-Free Survival (PFS) is defined as the period from the initial administration of the IP to disease progression (PD) or death. PFS assessed by the Investigator and evaluated according to RECIST 1.1 criteria. |
| Overall Survival(OS) | Baseline through the end of each 28-day cycle, up to 6 months. | Overall Survival(OS) is defined as the period from the initial administration of the IP to death. |
Countries
South Korea
Contacts
CONTACTAptamer Sciences Inc.
STUDY_DIRECTORDavid Lee
Aptamer Sciences, Inc.
Outcome results
None listed