This is an open-label, multi-center, phase 1/2 dose-escalation and dose expansion study evaluating the safety, tolerability, pharmacokinetics (PK), and anti-tumor activity of ML-016 in participants with advanced solid tumors with lung and/or liver involvement (primary or metastatic disease).
ML-016 will be administered intravenously as a monotherapy to assess safety, tolerability, pharmacokinetics (PK), and anti-tumor activity in participants with advanced/metastatic solid tumors with lung and/or liver involvement. The involvement of the lung and/or liver can involve primary or metastatic disease. Participants eligible for treatment include those whose disease is refractory to standard therapeutic options or for which no standard measures with curative intent or likelihood of disease control are available, or such measures are not acceptable to the participant. Participants will be administered ML-016 on Day 1 of each 21-day cycle. Treatment may continue until the participant's disease worsens or another treatment discontinuation criterion is met. Phase 1 will be a standard dose escalation design, and Phase 2 will be a dose expansion design evaluating two doses in disease-specific cohorts.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
108
a pH-sensitive polymeric doxorubicin formulated in a nanoporous silicon microparticle
Southside Cancer Care Centre
Miranda, New South Wales, Australia
Illawarra Cancer Care Center, Wollongong Hospital
Wollongong, New South Wales, Australia
Sunshine Coast Haematology and Oncology Clinic
Buderim, Queensland, Australia
Incidence of dose-limiting toxicities (DLTs) during the DLT assessment period
The incidence of dose-limiting toxicities (DLTs) graded per the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0 during the DLT assessment period
Time frame: Days 1-21 of the first cycle of study treatment (DLT assessment period)
Frequency and severity of adverse events (AEs) and serious AEs (SAEs)
The frequency and severity of adverse events (AEs) and serious AEs (SAEs), treatment discontinuations due to toxicity, and clinical laboratory abnormalities
Time frame: From first dose of study drug through 30 days following the last dose of study drug
Maximum tolerated dose (MTD) and doses recommended for expansion
Identify the MTD or maximum tested dose and doses recommended for expansion
Time frame: Days 1-21 of the first cycle of study treatment (DLT assessment period)
Vital Signs: Blood Pressure
Incidence and severity of changes in blood pressure from baseline
Time frame: Baseline and every cycle of study drug (each cycle is 21 days) through 30 days following the last dose of study drug
Vital Signs: Heart Rate
Incidence and severity of changes in heart rate from baseline
Time frame: Baseline and every cycle of study drug (each cycle is 21 days) through 30 days following the last dose of study drug
Electrocardiograms (ECGs): QT Interval
Incidence and severity of changes in ECG QT Interval from baseline
Time frame: Baseline and every cycle of study drug (each cycle is 21 days) through 30 days following the last dose of study drug
Amanda Jubb, Clinical Project Manager, Southern Star Research
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Echocardiograms (ECHO): LVEF
Incidence and severity of changes in LVEF from baseline
Time frame: Baseline and every cycle of study drug (each cycle is 21 days) through 30 days following the last dose of study drug
Disease control rate (DCR)
Disease control rate (DCR) is defined as the percentage of patients who have achieved complete response (CR), partial response (PR), or stable disease (SD) per RECIST 1.1.
Time frame: At least 42 days after the first dose of investigational product
Overall response rate (ORR)
Overall response rate (ORR) is defined as the percentage of patients who have achieved CR or PR per RECIST 1.1.
Time frame: From first dose of study drug through 12 months following first dose
Duration of response (DOR)
Duration of response (DOR) is defined as the time from the date measurement criteria are first met for patients who achieve PR or CR, to the date measurement criteria are first met for PD.
Time frame: Time from the date measurement criteria are first met for patients who achieve PR or CR, to the date measurement criteria are first met for PD, assessed up to 12 months.
Progression-free survival (PFS)
Progression-free survival (PFS) is defined as the time from the date of initiation of study treatment to the date measurement criteria are first met for PD or death from any cause, whichever occurs first.
Time frame: Time from the date of initiation of study treatment to the date measurement criteria are first met for PD or death from any cause, whichever occurs first, assessed up to 12 months.
Time to Progression (TTP)
Time to Progression (TTP) is defined as the time from the date of initiation of study treatment to the date that the measurement criteria are first met for PD.
Time frame: Time from the date of initiation of study treatment to the date that the measurement criteria are first met for PD, assessed up to 12 months.
Overall Survival (OS)
Overall Survival (OS) is defined as the time from the date of initiation of study treatment to the date of death from any cause.
Time frame: Time from the date of initiation of study treatment to the date of death from any cause, assessed up to 12 months.
Pharmacokinetic Profile: Cmax
Cmax: Maximum peak plasma concentration
Time frame: From first dose of study drug through 21 days following the first dose of study treatment (1 cycle)
Pharmacokinetic Profile: AUClast
AUClast: Area under the concentration-time curve from Hour 0 through the last quantifiable concentration time (LQCT), where LQCT is the time at which the last sample with a quantifiable concentration was drawn
Time frame: From first dose of study drug through 21 days following the first dose of study treatment (1 cycle)
Pharmacokinetic Profile: T½
T½: Half-life
Time frame: From first dose of study drug through 21 days following the first dose of study treatment (1 cycle)