Clinical trial NCT06687941: A Study to Evaluate the Tolerability, Safety, and PK of AST-201 in Patients With GPC3-positive Advanced Solid Tumors
Official title: A Multi-center, Open-label, Dose Escalation and Expansion, Phase 1 Study to Evaluate the Tolerability, Safety and Pharmacokinetics of AST-201 in Patients With GPC3-positive Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Neoplasms
Carcinoma, Hepatocellular
Carcinoma, Non-Small-Cell Lung
Liver Neoplasms
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
Lead sponsor: Aptamer Sciences, Inc.
Sponsor class: INDUSTRY
Collaborators: name: CHA University
name: National Cancer Center, Korea
name: Samsung Medical Center
name: Severance Hospital
First posted: 2024-11-14
Enrollment: 70
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Dose Limiting Toxicity (DLT)
timeFrame: 4 weeks
Secondary outcomes:
measure: Pharmacokinetics (PK)
timeFrame: Cycle 1, Days 1-2 (cycle is 28 days)
measure: Pharmacokinetics (PK)
timeFrame: Cycle 1, Days 1-2 (cycle is 28 days)
measure: Pharmacokinetics (PK)
timeFrame: Cycle 1, Days 1-2 (cycle is 28 days)
measure: Pharmacokinetics (PK)
timeFrame: Cycle 1, Days 1-2 (cycle is 28 days)
measure: Pharmacokinetics (PK)
timeFrame: Cycle 1, Days 1-2 (cycle is 28 days)
measure: Preliminary Antitumor Efficacy
timeFrame: Baseline through the end of each 28-day cycle, up to 6 months.
measure: Preliminary Antitumor Efficacy
timeFrame: Baseline through the end of each 28-day cycle, up to 6 months.
measure: Preliminary Antitumor Efficacy
timeFrame: Baseline through the end of each 28-day cycle, up to 6 months.
measure: Preliminary Antitumor Efficacy
timeFrame: Baseline through the end of each 28-day cycle, up to 6 months.
measure: Preliminary Antitumor Efficacy
timeFrame: Baseline through the end of each 28-day cycle, up to 6 months.
measure: Preliminary Antitumor Efficacy
timeFrame: Baseline through the end of each 28-day cycle, up to 6 months.
Other outcomes:
Locations:
city: Gyeonggi
country: Korea, Republic of
facility: National Cancer Center, Korea
city: Seongnam
country: Korea, Republic of
facility: CHA Bundang Medical Center
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
Study officials:
References: