Evaluating ISM6331 for advanced malignant mesothelioma and solid tumors

A Phase 1, Open-Label, Multicenter, FIH Study to Evaluate the Safety, Tolerability, Pharmacokinetics/Pharmacodynamics, and Preliminary Efficacy of ISM6331 in Participants With Advanced/Metastatic Malignant Mesothelioma or Other Solid Tumors

This study is testing a new drug called ISM6331 to see if it is safe and effective for people with advanced malignant mesothelioma and other solid tumors who haven't had success with standard treatments.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 100 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: InSilico Medicine Hong Kong Limited (industry)
• Drugs / interventions: chemotherapy
• Locations: 10 sites (Denver, Colorado and 9 other locations)
• Trial ID: NCT06566079 on ClinicalTrials.gov

What this trial studies

This Phase 1, open-label, multicenter study aims to assess the safety, tolerability, and preliminary anti-tumor activity of ISM6331 in patients with advanced or metastatic malignant mesothelioma and other solid tumors. The trial consists of two parts: a dose escalation phase to determine the recommended Phase 2 dose and a dose selection optimization phase. Participants must have disease progression after standard therapies or be intolerant to them, and the study will evaluate the drug's pharmacokinetics and pharmacodynamics.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with unresectable advanced or metastatic malignant mesothelioma or other solid tumors who have progressed after standard therapies.

Not a fit: Patients with early-stage tumors that are resectable or those who have not yet undergone standard treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced malignant mesothelioma and other solid tumors who have limited treatment options.

How similar studies have performed: While this approach is novel in targeting the Hippo pathway with ISM6331, similar studies targeting other pathways have shown promise in treating solid tumors.

Eligibility criteria

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.

Where this trial is running

Denver, Colorado and 9 other locations

• Sarah Cannon Research Institute at HealthONE — Denver, Colorado, United States (RECRUITING)
• The University of Chicago Medical Center - Duchossois Center for Advanced Medicine — Chicago, Illinois, United States (RECRUITING)
• University Hospitals Cleveland Medical Center — Cleveland, Ohio, United States (RECRUITING)
• University of Pennsylvania - Abramson Cancer Center — Philadelphia, Pennsylvania, United States (RECRUITING)
• SCRI Oncology Partners — Nashville, Tennessee, United States (RECRUITING)
• NEXT Oncology - Austin — Austin, Texas, 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)

Study contacts

• Study coordinator: Qinhan Chen

Conditions: Malignant Mesothelioma, Metastatic Malignant Solid Tumor, Advanced Solid Tumor, Transcriptional enhanced associate domain, TEAD inhibitor, ISM6331, Hippo pathway, YAP/TAZ-TEAD