This is a Phase 1, open-label, multicenter, FIH study to evaluate the safety, tolerability, recommended Phase 2 dose (RP2D), PK/PD, and preliminary anti-tumor activity of ISM6331 in participants with advanced or metastatic malignant mesothelioma or other solid tumors. The study consists of two parts, a dose escalation part (Part 1) and a dose selection optimization part (Part 2).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
100
Dosage form: Capsule for oral administration. Frequency of administration: Once daily overall of treatment.
Sarah Cannon Research Institute at HealthONE
Denver, Colorado, United States
RECRUITINGThe University of Chicago Medical Center - Duchossois Center for Advanced Medicine
Chicago, Illinois, United States
RECRUITINGUniversity Hospitals Cleveland Medical Center
Cleveland, Ohio, United States
RECRUITINGUniversity of Pennsylvania - Abramson Cancer Center
Philadelphia, Pennsylvania, United States
RECRUITINGSCRI Oncology Partners
Nashville, Tennessee, United States
RECRUITINGNEXT Oncology - Austin
Austin, Texas, United States
RECRUITINGHenan Cancer Hospital
Zhengzhou, Henan, China
RECRUITINGShanghai Pulmonary Hospital
Shanghai, Shanghai Municipality, China
NOT_YET_RECRUITINGCancer Hospital Chinese Academy of Medical Sciences
Beijing, China
RECRUITINGSun Yat-Sen University Cancer Center
Guangzhou, China
RECRUITINGIncidence of dose-limiting toxicity (DLT).
DLT is defined as any adverse event which meets DLT criteria unless it is clearly related to disease progression or intercurrent illness during the first 31 days after the initiation of treatment in the dose escalation part (Part 1).
Time frame: Day 1 up to Day 31
Incidence and severity of adverse events (AEs)
Adverse events are assessed based on the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 \[NCI CTCAE v5.0\]
Time frame: Approximately 12 months.
Incidence of clinically significant abnormalities in laboratory values, vital signs, physical examination, and electrocardiogram (ECG) measurements.
Regular monitoring and assessment of vital signs (pulse rate, blood pressure, respiratory rate, and temperature), physical examinations, laboratory values, ECG, and other safety examinations by investigators.
Time frame: Approximately 12 months.
Recommended Phase 2 Dose (RP2D)
The RP2D will be recommended by safety review committee (SRC) upon reviewing all available safety, tolerability, pharmacokinetics/pharmacodynamics, and preliminary efficacy data from Part 1 and Part 2.
Time frame: Approximately 40 months
Maximum observed concentration (Cmax)
Pharmacokinetics (PK) parameters of ISM6331 after dose of ISM6331 will be assessed.
Time frame: Approximately 12 months
Area under the concentration-time curve (AUC)
Pharmacokinetics (PK) parameters of ISM6331 after dose of ISM6331 will be assessed.
Time frame: Approximately 12 months
Terminal half-life (t1/2)
Pharmacokinetics (PK) parameters of ISM6331 after dose of ISM6331 will be assessed.
Time frame: Approximately 12 months
Objective response rate (ORR).
Efficacy assessments will be conducted at baseline and every 8 weeks within the first 6 months after the first dose of study treatment, then every 12 weeks thereafter, until progressive disease confirmed by the investigator, start of a new anti-tumor treatment, death, lost to follow-up, or withdrawal from the study, whichever occurs first.
Time frame: Approximately 12 months
Best objective response (BOR).
Efficacy assessments will be conducted at baseline and every 8 weeks within the first 6 months after the first dose of study treatment, then every 12 weeks thereafter, until progressive disease confirmed by the investigator, start of a new anti-tumor treatment, death, lost to follow-up, or withdrawal from the study, whichever occurs first.
Time frame: Approximately 12 months
Duration of response (DoR).
Efficacy assessments will be conducted at baseline and every 8 weeks within the first 6 months after the first dose of study treatment, then every 12 weeks thereafter, until progressive disease confirmed by the investigator, start of a new anti-tumor treatment, death, lost to follow-up, or withdrawal from the study, whichever occurs first.
Time frame: Approximately 12 months
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