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

Phase 1

Not yet recruiting

• Conditions: Metastatic Malignant Solid Tumor; Malignant Mesothelioma; Advanced Solid Tumor
• Interventions: Drug: ISM6331

• Registration Number: NCT06566079
• Lead Sponsor: InSilico Medicine Hong Kong Limited

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 optim...

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design

Study Timeline

• Study First Submitted: 2024-08-13
• Study First Submitted QC: 2024-08-19
• Study First Posted: 2024-08-22
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-05
• Last Update Posted: 2024-12-06
• Study Start: 2024-12-30
• Primary Completion: 2027-08-31
• Study Completion: 2028-02-28

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 82

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 disease progression after standard therapy, intolerable to standard therapy, or for whom no 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. For participants with malignant mesothelioma, prior treatment of ≥2 regimens are required, including but not limit to immune checkpoint therapy.
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.

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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.

Other protocol inclusion and exclusion criteria may apply.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Part 2 Dose Selection Optimization	ISM6331	Participants will receive ISM6331 once daily at each dose level from the two dose levels recommended by Study Review Committee.
Part 1 Dose Escalation	ISM6331	Patients will receive ISM6331 once daily in sequential cohorts of increasing doses.

Primary Outcome Measures

Name	Time	Method
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.

Secondary Outcome Measures

Name	Time	Method
Area under the concentration-time curve (AUC)	Approximately 12 months	Pharmacokinetics (PK) parameters of ISM6331 after dose of ISM6331 will be assessed.
Maximum observed concentration (Cmax)	Approximately 12 months	Pharmacokinetics (PK) parameters of ISM6331 after dose of ISM6331 will be assessed.
Terminal half-life (t1/2)	Approximately 12 months	Pharmacokinetics (PK) parameters of ISM6331 after dose of ISM6331 will be assessed.
Best objective response (BOR).	Approximately 12 months	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.
Objective response rate (ORR).	Approximately 12 months	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.
Duration of response (DoR).	Approximately 12 months	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.