This is a multicenter, open-label, Phase 1, first-in-human, dose-escalation study designed to assess the safety, tolerability and define the RP2D of MT-303 alone (Module 1) and in combination with Atezo/Bev (Module 2) in participants with advanced hepatocellular carcinoma expressing GPC3.
Participants will be enrolled into one of two treatment modules: * Module 1 (Monotherapy): Participants will receive MT-303. * Module 2 (Combination therapy): Participants will receive MT-303 in combination with atezolizumab + bevacizumab (Atezo/Bev). In Module 1 (Monotherapy), participants will receive MT-303 across five dose-escalation cohorts and in Module 2 (Combination therapy), participants will receive MT-303 in combination with Atezo/Bev across five dose-escalation cohorts. Additional cohorts in both modules may be scheduled based on emerging safety and PK data. Participants will be sequentially enrolled into Cohorts 1 through 5. Both modules will be enrolled concurrently, with Module 2 dosing beginning at one dose level below the known safe dose in Module 1. Safety Review Committee decisions will be informed by all available safety data from Modules 1 and 2.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
70
MT-303
MT-303 in combination with Atezo/Bev
St Vincent's Hospital
Sydney, New South Wales, Australia
RECRUITINGIntegrated Clinical Oncology Network (ICON) Pty Ltd
Woolloongabba, Queensland, Australia
RECRUITINGThe Alfred Hospital
Type, incidence and severity of Adverse Events
Safety and tolerability profile assessed by the Common Terminology Criteria for Adverse Events v5.0
Time frame: Up to 2 years from the last dose of Investigational Medicinal Product (IMP)
Recommended Phase 2 Dose (RP2D)
The RP2D will be determined using dose limiting toxicities (DLTs) and all other available study data
Time frame: 28 days from the last dose of IMP
Optimal Biological dose (OBD)
The OBD will be determined using dose limiting toxicities (DLTs) and all other available study data
Time frame: 21 days from the last dose of IMP
Change from baseline in vital signs
Temperature, weight, height, pulse rate and blood pressure will be assessed
Time frame: Up to 30 days from the last dose of IMP
Change in laboratory parameters
Hematology, chemistry, coagulation, virology and urine analysis will be assessed.
Time frame: Up to 30 days from the last dose of IMP
Change from baseline in ECG parameters
Time frame: Screening, Day 1 and Day 15
Pharmacokinetics (PK)
PK parameter: Plasma concentrations
Time frame: Day 1, 2, 3, 8, 15 and once every 28 days post first dose of IMP for Module 1 and Day 1, 2, 8 and once every 21 days post first dose of IMP for Module 2.
Pharmacokinetics (PK)
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Melbourne, Victoria, Australia
Linear Clinical Research
Murdoch, Western Australia, Australia
RECRUITINGPusan National Univesity Hospital
Busan, South Korea
RECRUITINGCha University Bundang Medical Center
Gyeonggi-do, South Korea
RECRUITINGSeoul National University Hospital
Seoul, South Korea
RECRUITINGNational Taiwan University Hospital
Taipei, Taiwan
RECRUITINGTaipei Tzu Chi Hospital
Taipei, Taiwan
RECRUITINGPK parameter: Area under Curve
Time frame: Day 1, 2, 3, 8, 15 and once every 28 days post first dose of IMP for Module 1 and Day 1, 2, 8 and once every 21 days post first dose of IMP for Module 2.
Pharmacokinetics (PK)
PK parameter: Time of maximum observed plasma concentration (tmax)
Time frame: Day 1, 2, 3, 8, 15 and once every 28 days post first dose of IMP for Module 1 and Day 1, 2, 8 and once every 21 days post first dose of IMP for Module 2.
Pharmacokinetics (PK)
PK parameter: Plasma Clearance (CL)
Time frame: Day 1, 2, 3, 8, 15 and once every 28 days post first dose of IMP for Module 1 and Day 1, 2, 8 and once every 21 days post first dose of IMP for Module 2.
Pharmacokinetics (PK)
PK parameter: Volume of Distribution (Vd)
Time frame: Day 1, 2, 3, 8, 15 and once every 28 days post first dose of IMP for Module 1 and Day 1, 2, 8 and once every 21 days post first dose of IMP for Module 2.
Pharmacokinetics (PK)
PK parameter: Mean residence time (MRT)
Time frame: Day 1, 2, 3, 8, 15 and once every 28 days post first dose of IMP for Module 1 and Day 1, 2, 8 and once every 21 days post first dose of IMP for Module 2.
Pharmacokinetics (PK)
PK parameter: terminal rate constant (λz)
Time frame: Day 1, 2, 3, 8, 15 and once every 28 days post first dose of IMP for Module 1 and Day 1, 2, 8 and once every 21 days post first dose of IMP for Module 2.
To assess adverse events of special interest (AESI) by measuring infusion reaction
Time frame: upto 2 years from the last dose of IMP
To assess adverse events of special interest (AESI) by measuring cytokine release syndrome (CRS)
Time frame: Up to 2 years from the last dose of IMP
To assess adverse events of special interest (AESI) by measuring immune effector cell-associated neurotoxicity syndrome (ICANS)
Time frame: Up to 2 years from the last dose of IMP
To assess adverse events of special interest (AESI) by measuring hypersensitivity reaction
Time frame: Up to 2 years from the last dose of IMP
To assess adverse events of special interest (AESI) by checking for second primary malignancy
Time frame: upto 2 years from the last dose of IMP