Malignant MesotheliomaPhase 1/2NCT06566079
Study of ISM6331 in Participants With Advanced/Metastatic Mesothelioma or Other Advanced Solid Tumors
A Phase 1/2 study testing ISM6331 in people with Malignant Mesothelioma and Metastatic Malignant Solid Tumor, run by InSilico Medicine Hong Kong Limited at 10 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Mesothelioma, Metastatic Malignant Solid Tumor, Advanced Solid Tumor
- What is being tested?
- ISM6331
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 160 participants
- Where
- 10 sitesin 2 countries
- Study dates
- 27 Dec 2024to 28 Feb 2028
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female participants with age ≥18 years at the time of signing the informed consent.
- 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.
- 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.
Who cannot join
- 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
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- 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.
- Other protocol inclusion and exclusion criteria may apply.
Trial locations and contacts
10 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
10 sites in 2 countries
United States6 sites, 6 recruiting
- Recruiting
NEXT Oncology - Austin
Austin, Texas, 78758
- Recruiting
The University of Chicago Medical Center - Duchossois Center for Advanced Medicine
Chicago, Illinois, 60637
- Recruiting
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106
- Recruiting
Sarah Cannon Research Institute at HealthONE
Denver, Colorado, 80218
- Recruiting
SCRI Oncology Partners
Nashville, Tennessee, 37203
- Recruiting
University of Pennsylvania - Abramson Cancer Center
Philadelphia, Pennsylvania, 19104
China4 sites, 4 recruiting
- Recruiting
Cancer Hospital Chinese Academy of Medical Sciences
Beijing
- Recruiting
Sun Yat-Sen University Cancer Center
Guangzhou
- Recruiting
Shanghai Pulmonary Hospital
Shanghai, Shanghai Municipality
- Recruiting
Henan Cancer Hospital
Zhengzhou, Henan
About this study
Official title: A Phase 1/2, Open-Label, Multicenter, FIH Study to Evaluate the Safety, Tolerability, Pharmacokinetics/Pharmacodynamics, and Preliminary Efficacy of ISM6331 in Participants With Advanced/Metastatic Mesothelioma or Other Advanced Solid Tumors
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).
- Being tested
- ISM6331
- Keywords
- Transcriptional enhanced associate domain (TEAD), TEAD inhibitor, ISM6331, Hippo pathway, YAP/TAZ-TEAD
- Medical subject headings
- Mesothelioma, Malignant, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ISM6331Drug
Dosage form: Capsule for oral administration.
Frequency of administration: Once daily overall of treatment.
| Study group | Role | What they receive |
|---|---|---|
| Part 1 Dose Escalation | Experimental | Patients will receive ISM6331 once daily in sequential cohorts of increasing doses. Receives: 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. Receives: Drug: ISM6331 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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]
Measured: 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.
Measured: 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.
Measured: Approximately 40 months
Secondary outcomes (6)
Maximum observed concentration (Cmax)
Pharmacokinetics (PK) parameters of ISM6331 after dose of ISM6331 will be assessed.
Measured: Approximately 12 months
Area under the concentration-time curve (AUC)
Pharmacokinetics (PK) parameters of ISM6331 after dose of ISM6331 will be assessed.
Measured: Approximately 12 months
Terminal half-life (t1/2)
Pharmacokinetics (PK) parameters of ISM6331 after dose of ISM6331 will be assessed.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Approximately 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Aug 2024
- Study start27 Dec 2024
- Primary completion31 Aug 2027 (estimated)
- Study completion28 Feb 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Malignant MesotheliomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 160 participants (estimated)
Sponsor and investigators
- Lead sponsor
- InSilico Medicine Hong Kong Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06566079
- Sponsor's protocol ID
- ISM6331-101
- Status last verified
- Jul 2026
- First submitted
- 13 Aug 2024
- Last updated
- 16 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2, Open-Label, Multicenter, FIH Study to Evaluate the Safety, Tolerability, Pharmacokinetics/Pharmacodynamics, and Preliminary Efficacy of ISM6331 in Participants With Advanced/Metastatic Mesothelioma or Other Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT06566079
- Acronym / sponsor ID
- ISM6331-101
- Keywords
- Transcriptional enhanced associate domain (TEAD), TEAD inhibitor, ISM6331, Hippo pathway, YAP/TAZ-TEAD
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 160 participants (estimated)
- Lead sponsor
- InSilico Medicine Hong Kong LimitedIndustry (pharma, biotech, devices)
- Study start
- 27 Dec 2024 (actual)
- Primary completion
- 31 Aug 2027 (estimated)
- Study completion
- 28 Feb 2028 (estimated)
- First posted
- 22 Aug 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Part 1 Dose Escalation | Experimental | Drug: ISM6331Patients will receive ISM6331 once daily in sequential cohorts of increasing doses. |
| Part 2 Dose Selection Optimization | Experimental | Drug: ISM6331Participants will receive ISM6331 once daily at each dose level from the two dose levels recommended by Study Review Committee. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Male or female participants with age ≥18 years at the time of signing the informed consent.
- 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.
- 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.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ISM6331Dosage form: Capsule for oral administration. Frequency of administration: Once daily overall of treatment. | Drug | Part 1 Dose Escalation, Part 2 Dose Selection Optimization |
Primary outcome
Incidence of dose-limiting toxicity (DLT).
Time frame: 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)
Time frame: 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.
Time frame: 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)
Time frame: 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.
6 secondary outcomes
Maximum observed concentration (Cmax)
Time frame: Approximately 12 months
Area under the concentration-time curve (AUC)
Time frame: Approximately 12 months
Terminal half-life (t1/2)
Time frame: Approximately 12 months
Objective response rate (ORR).
Time frame: Approximately 12 months
Best objective response (BOR).
Time frame: Approximately 12 months
Duration of response (DoR).
Time frame: Approximately 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Sep 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
10 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ISM6331 in people with Malignant Mesothelioma and Metastatic Malignant Solid Tumor, run by InSilico Medicine Hong Kong Limited at 10 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 16 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States, China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Qinhan Chen (+86 021-50831718, Insilico-Clinicaltrial@insilico.ai), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of dose-limiting toxicity (DLT). (time frame: Day 1 up to Day 31). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Sep 2026.