Study of ISM6331 in Participants With Advanced/Metastatic Malignant Mesothelioma or Other Solid Tumors

NCT06566079 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: ISM6331-101
• Study Type: interventional
• Target: 100
• Locations: 2 countries
• Sites: 10

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

Keywords

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

Outcome Measures

Primary Outcomes (4)

• Incidence 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).

  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 \[NCI CTCAE v5.0\]

  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.

  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.

  Approximately 40 months

Secondary Outcomes (6)

• Maximum observed concentration (Cmax)

  Approximately 12 months

• Area under the concentration-time curve (AUC)

  Approximately 12 months

• Terminal half-life (t1/2)

  Approximately 12 months

• Objective response rate (ORR).

  Approximately 12 months

• Best objective response (BOR).

  Approximately 12 months

Study Arms (2)

Part 1 Dose Escalation

EXPERIMENTAL

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

Drug: ISM6331

Part 2 Dose Selection Optimization

EXPERIMENTAL

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

Drug: ISM6331

Interventions

ISM6331 DRUG

Dosage form: Capsule for oral administration. Frequency of administration: Once daily overall of treatment.

Part 1 Dose Escalation; Part 2 Dose Selection Optimization

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female participants with age ≥18 years at the time of signing the informed consent.
• 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.
• Participants with malignant mesothelioma must have prior exposure to at least immune checkpoint therapy and platinum-based chemotherapy.
• 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.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤1.
• Life expectancy of ≥12 weeks as judged by the investigator.
• Adequate organ function as determined by medical assessment (within 7 days prior to the first dose of study treatment).
• Capable of providing signed informed consent form (ICF) and complying with the requirements and restrictions listed in the ICF and in this study protocol.

You may not qualify if:

• Participants who have previously received a TEAD inhibitor.
• Participation in other therapeutic clinical studies within 28 days or 5 half-lives (whichever is shorter) prior to first dose of study treatment.
• Anti-tumor therapy within 28 days or 5 half-lives (whichever is shorter) prior to first dose of study treatment.
• Known active central nervous system (CNS) primary tumor or untreated CNS metastases.
• As judged by the investigator, any evidence of severe or uncontrolled systemic diseases.
• Unwillingness or unable to comply with the requirements of oral drug administration, or presence of a gastro-intestinal condition
• 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.
• 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.

Sponsors & Collaborators

• InSilico Medicine Hong Kong Limited: lead

Study Sites (10)

Sarah Cannon Research Institute at HealthONE

Denver, Colorado, 80218, United States

RECRUITING

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

Chicago, Illinois, 60637, United States

RECRUITING

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

RECRUITING

University of Pennsylvania - Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

SCRI Oncology Partners

Nashville, Tennessee, 37203, United States

RECRUITING

NEXT Oncology - Austin

Austin, Texas, 78758, United States

RECRUITING

Henan Cancer Hospital

Zhengzhou, Henan, China

RECRUITING

Shanghai Pulmonary Hospital

Shanghai, Shanghai Municipality, China

NOT YET RECRUITING

Cancer Hospital Chinese Academy of Medical Sciences

Beijing, China

RECRUITING

Sun Yat-Sen University Cancer Center

Guangzhou, China

RECRUITING

MeSH Terms

Conditions

Mesothelioma, Malignant; Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Mesothelioma; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Qinhan Chen

CONTACT

+86 021-50831718; Insilico-Clinicaltrial@insilico.ai

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 13, 2024
• First Posted: August 22, 2024
• Study Start: December 27, 2024
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): February 28, 2028
• Last Updated: February 17, 2026

Record last verified: 2025-09

Locations

US (6); CN (4)