This clinical trial is designed to evaluate the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of MT-304 in adults with advanced HER2-expressing solid tumors. The main questions it aims to answer are: * What is the safety profile of MT-304 when administered alone or with nivolumab? * What is the recommended Phase 2 dose (RP2D) of MT-304? Participants will: * Receive MT-304 alone (every 14 days) or with nivolumab (every 28 days). * Attend regular clinic visits for assessments and monitoring. * Continue treatment until disease progression, unacceptable toxicity, or study discontinuation.
This multicenter, open-label, Phase 1 trial is designed to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of MT-304 in adults aged 18 and older with advanced HER2-expressing solid tumors. The study consists of two treatment modules: * Module 1 (Monotherapy): Participants receive MT-304 every 14 days for 28-day cycles, with dosing adjustments based on clinical benefit and safety evaluations. * Module 2 (Combination Therapy): Participants receive MT-304 in combination with nivolumab, administered every 14 days and 28 days, respectively, also allowing for dosing adjustments. The Bayesian Optimal Interval (BOIN) design will guide dose escalation, overseen by a Safety Review Committee to establish the recommended Phase 2 dose (RP2D). Regular assessments, including vital signs and laboratory tests, will monitor safety and efficacy throughout the trial, with follow-up visits for up to 2 years post-treatment.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
60
Safety, tolerability, and pharmacokinetics will be evaluated.
Combination therapy begins after monotherapy dose clearance by the Safety Review Committee.
Calvary Mater Newcastle
Waratah, New South Wales, Australia
RECRUITINGScientia Clinical Research Ltd
Randwick, New South Wales (nsw), Australia
RECRUITINGLinear Clinical Research
Nedlands, Western Australia, Australia
RECRUITINGType, incidence and severity of Adverse Events
Safety and tolerability profile assessed by the Common Terminology Criteria for Adverse Events v5.
Time frame: Up to 90 days from the last dose of Investigational Medicinal Product (IMP)
Number of Participants With Change From Baseline in Vital Signs (Composite Safety Outcome)
Body temperature, body weight, pulse rate, and blood pressure (systolic and diastolic) assessed collectively; participants with clinically significant changes in any vital sign parameter will be summarized as a composite safety outcome.
Time frame: Up to 30 days from the last dose of IMP
Number of Participants With Abnormal Clinical Laboratory Parameters (Composite Safety Outcome)
Hematology, clinical chemistry, coagulation, virology testing, and urinalysis assessed collectively; participants with abnormalities in any laboratory parameter will be summarized as a composite safety outcome.
Time frame: Up to 30 days from the last dose of IMP
Number of Participants With Change From Baseline in ECG Parameters (Composite Safety Outcome)
PR interval, QRS duration, QT interval, corrected QT interval (QTc), and heart rate assessed collectively from 12-lead ECG recordings; participants with clinically significant changes in any ECG parameter will be summarized as a composite safety outcome.
Time frame: Screening through Day 28, with assessments performed on Screening, Day 1 (pre-dose), and Day 28.
Maximum Tolerated Dose (MTD)
The MTD in Module 1 (monotherapy) will be determined based on dose-limiting toxicities (DLTs).
Time frame: 28 days from the last dose of IMP
Optimal Biological Dose (OBD)
The OBD in Module 2 (combination) will be identified based on dose-limiting toxicities (DLTs).
Time frame: 28 days from the last dose of IMP
Pharmacokinetics (PK)
PK Parameter: Maximum plasma concentration (Cmax)
Time frame: From Day 1, Day 2, Day 8, and Day 15 of Cycles 1 and 2, and Day 1 of Cycle 3 (each cycle is 28 days).
Pharmacokinetics (PK)
PK parameter: Area under Curve
Time frame: From Day 1, Day 2, Day 8, and Day 15 of Cycles 1 and 2, and Day 1 of Cycle 3 (each cycle is 28 days).
Pharmacokinetics (PK)
PK parameter: Time of maximum observed plasma concentration (tmax)
Time frame: From Day 1, Day 2, Day 8, and Day 15 of Cycles 1 and 2, and Day 1 of Cycle 3 (each cycle is 28 days).
Pharmacokinetics (PK)
PK parameter:Terminal half-life (t½)
Time frame: From Day 1, Day 2, Day 8, and Day 15 of Cycles 1 and 2, and Day 1 of Cycle 3 (each cycle is 28 days).
Pharmacokinetics (PK)
PK parameter: Plasma Clearance (CL)
Time frame: From Day 1, Day 2, Day 8, and Day 15 of Cycles 1 and 2, and Day 1 of Cycle 3 (each cycle is 28 days).
Pharmacokinetics (PK)
PK parameter: Volume of Distribution (Vd)
Time frame: From Day 1, Day 2, Day 8, and Day 15 of Cycles 1 and 2, and Day 1 of Cycle 3 (each cycle is 28 days).
Pharmacokinetics (PK)
PK parameter: Mean residence time (MRT)
Time frame: From Day 1, Day 2, Day 8, and Day 15 of Cycles 1 and 2, and Day 1 of Cycle 3 (each cycle is 28 days).
To assess adverse events of special interest (AESI) by measuring infusion reaction
Time frame: Upto 90 days from the last dose of IMP
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To assess adverse events of special interest (AESI) by measuring cytokine release syndrome (CRS)
Time frame: Upto 90 days 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: Upto 90 days from the last dose of IMP
To assess adverse events of special interest (AESI) by measuring hypersensitivity reaction
Time frame: Upto 90 days from the last dose of IMP
To assess the incidence of second primary malignancies reported as adverse events of special interest (AESI) occurring during the study treatment period and long-term follow-up.
Time frame: From first dose of Investigational Medicinal Product (IMP) through end of study and follow-up (up to 2 years)