Clinical trial NCT06566079: Study of ISM6331 in Participants With Advanced/Metastatic Malignant Mesothelioma or Other Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Malignant Mesothelioma
Metastatic Malignant Solid Tumor
Advanced Solid Tumor
Keywords: Transcriptional enhanced associate domain (TEAD)
TEAD inhibitor
ISM6331
Hippo pathway
YAP/TAZ-TEAD
Lead sponsor: InSilico Medicine Hong Kong Limited
Sponsor class: INDUSTRY
First posted: 2024-08-22
Enrollment: 82
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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).


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 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.

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.

Primary outcomes:
measure: Incidence of dose-limiting toxicity (DLT).
timeFrame: Day 1 up to Day 31
measure: Incidence and severity of adverse events (AEs)
timeFrame: Approximately 12 months.
measure: Incidence of clinically significant abnormalities in laboratory values, vital signs, physical examination, and electrocardiogram (ECG) measurements.
timeFrame: Approximately 12 months.
measure: Recommended Phase 2 Dose (RP2D)
timeFrame: Approximately 40 months
Secondary outcomes:
measure: Maximum observed concentration (Cmax)
timeFrame: Approximately 12 months
measure: Area under the concentration-time curve (AUC)
timeFrame: Approximately 12 months
measure: Terminal half-life (t1/2)
timeFrame: Approximately 12 months
measure: Objective response rate (ORR).
timeFrame: Approximately 12 months
measure: Best objective response (BOR).
timeFrame: Approximately 12 months
measure: Duration of response (DoR).
timeFrame: Approximately 12 months
Other outcomes:
Locations:
city: Denver
country: United States
facility: Sarah Cannon Research Institute at HealthONE
state: Colorado
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania - Abramson Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: SCRI Oncology Partners
state: Tennessee
city: Austin
country: United States
facility: NEXT Oncology - Austin
state: Texas
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Sciences
city: Guangzhou
country: China
facility: Sun Yat-Sen University Cancer Center
Study officials:
References: