Recruiting
Phase 1

ISM6331

Sponsor:

InSilico Medicine Hong Kong Limited

Code:

NCT06566079

Conditions

Malignant Mesothelioma

Metastatic Malignant Solid Tumor

Advanced Solid Tumor

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

ISM6331

Study Details

Brief summary:

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).

Conditions

Malignant Mesothelioma

Metastatic Malignant Solid Tumor

Advanced Solid Tumor

Study ID

NCT06566079

Start date

Dec 27, 2024

Status verified date

Sep, 2025

Completion date

Feb 28, 2028

Anticipated

Primary completion date

Aug 31, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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 malignant mesothelioma or other 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.

Study Design

Enrollment

100 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Part 1 Dose Escalation

Patients will receive ISM6331 once daily in sequential cohorts of increasing doses.

experimental: Part 2 Dose Selection Optimization

Participants will receive ISM6331 once daily at each dose level from the two dose levels recommended by Study Review Committee.

Interventions

ISM6331

Dosage form: Capsule for oral administration.

Frequency of administration: Once daily overall of treatment.

Primary outcome measure

  • Incidence of dose-limiting toxicity (DLT). [ Time Frame: Day 1 up to Day 31 ]
  • Incidence and severity of adverse events (AEs) [ Time Frame: Approximately 12 months. ]
  • Incidence of clinically significant abnormalities in laboratory values, vital signs, physical examination, and electrocardiogram (ECG) measurements. [ Time Frame: Approximately 12 months. ]
  • Recommended Phase 2 Dose (RP2D) [ Time Frame: Approximately 40 months ]

Central Contacts and Locations

Locations

Sarah Cannon Research Institute at HealthONE

Recruiting

Denver, Colorado, United States, 80218

The University of Chicago Medical Center - Duchossois Center for Advanced Medicine

Recruiting

Chicago, Illinois, United States, 60637

University Hospitals Cleveland Medical Center

Recruiting

Cleveland, Ohio, United States, 44106

University of Pennsylvania - Abramson Cancer Center

Recruiting

Philadelphia, Pennsylvania, United States, 19104

SCRI Oncology Partners

Recruiting

Nashville, Tennessee, United States, 37203

NEXT Oncology - Austin

Recruiting

Austin, Texas, United States, 78758

More Information

Sponsor

InSilico Medicine Hong Kong Limited

Last update posted

Feb 17, 2026

Last verified

Sep, 2025

Keywords

  • Transcriptional enhanced associate domain (TEAD)
  • TEAD inhibitor
  • ISM6331
  • Hippo pathway
  • YAP/TAZ-TEAD

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by InSilico Medicine Hong Kong Limited on 2026-02-17.