ISM6331: Dosage form: Capsule for oral administration.
Frequency of administration: Once daily overall of treatment.
Study summary
This is a Phase 1/2, 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 mesothelioma or other Advanced solid tumors. The study consists of two parts, a dose escalation part (Part 1) and a dose selection expansion part (Part 2).
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria:
1. Male or female participants with age ≥18 years at the time of signing the informed consent.
2. Histologically confirmed unresectable advanced or metastatic mesothelioma or other advanced solid tumors, who have failed standard therapy or for whom no effective standard therapy exists, participants for part 1 is regardless of the presence or absence of the genetic alterations of the Hippo pathway, but for part 2 participants with solid tumors other than mesothelioma, genetic testing documentation must demonstrate Hippo signaling pathway dysregulation.
3. Participants with malignant mesothelioma must have prior exposure to at least immune checkpoint therapy and platinum-based chemotherapy.
4. Presence of at least one evaluable lesion in Part 1 or one measurable target lesion in Part 2 according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) for participants with non-pleural mesothelioma or other solid tumors and modified RECIST (mRECIST) v1.1 for participants with malignant pleural mesothelioma.
5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤1.
6. Life expectancy of ≥12 weeks as judged by the investigator.
7. Adequate organ function as determined by medical assessment (within 7 days prior to the first dose of study treatment).
8. Capable of providing signed informed consent form (ICF) and complying with the requirements and restrictions listed in the ICF and in this study protocol.
Exclusion Criteria:
1. Participants who have previously received a TEAD inhibitor.
2. Participation in other therapeutic clinical studies within 28 days or 5 half-lives (whichever is shorter) prior to first dose of study treatment.
3. Anti-tumor therapy within 28 days or 5 half-lives (whichever is shorter) prior to first dose of study treatment.
4. Known active central nervous system (CNS) primary tumor or untreated CNS metastases.
5. As judged by the investigator, any evidence of severe or uncontrolled systemic diseases.
6. Unwillingness or unable to comply with the requirements of oral drug administration, or presence of a gastro-intestinal condition
7. Have prior or ongoing clinically significant illness, medical condition, surgical history, physical finding, laboratory abnormality or any other conditions that, in the investigator's opinion, would not be in the best interest of the participant; or that could alter the absorption, distribution, metabolism, or excretion of the study treatment; or impair the assessment of study result.
8. Currently receiving any of Strong inhibitors or inducers of P-gp, or Sensitive substrates of P-gp, CYP1A2, CYP2B6, and CYP3A4 that cannot be discontinued 14 days or 5 half-lives for inhibitors or substrates (whichever is shorter) prior to the first dose of study treatment.
Other protocol inclusion and exclusion criteria may apply.
Primary outcome measure(s)
Incidence of dose-limiting toxicity (DLT). — Day 1 up to Day 31 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).
Incidence and severity of adverse events (AEs) — Approximately 12 months. Adverse events are assessed based on the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 \[NCI CTCAE v5.0\]
Incidence of clinically significant abnormalities in laboratory values, vital signs, physical examination, and electrocardiogram (ECG) measurements. — Approximately 12 months. 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.
Recommended Phase 2 Dose (RP2D) — Approximately 40 months 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.
Trial sites (10)
Facility
City
Region
Status
Sarah Cannon Research Institute at HealthONE
Denver
Colorado
Recruiting
The University of Chicago Medical Center - Duchossois Center for Advanced Medicine
Chicago
Illinois
Recruiting
University Hospitals Cleveland Medical Center
Cleveland
Ohio
Recruiting
University of Pennsylvania - Abramson Cancer Center
Philadelphia
Pennsylvania
Recruiting
SCRI Oncology Partners
Nashville
Tennessee
Recruiting
NEXT Oncology - Austin
Austin
Texas
Recruiting
Henan Cancer Hospital
Zhengzhou
Henan
Recruiting
Shanghai Pulmonary Hospital
Shanghai
Shanghai Municipality
Recruiting
Cancer Hospital Chinese Academy of Medical Sciences
Beijing
China
Recruiting
Sun Yat-Sen University Cancer Center
Guangzhou
China
Recruiting
More InSilico Medicine Hong Kong Limited trials in China
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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