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

Overview

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).

Interventions

• Drug ISM6331
  Dosage form: Capsule for oral administration. Frequency of administration: Once daily overall of treatment.

Primary outcome measures

• Incidence of dose-limiting toxicity (DLT). [Time frame: Day 1 up to Day 31]
• Incidence and severity of adverse events (AEs) [Time frame: Approximately 12 months.]
• Incidence of clinically significant abnormalities in laboratory values, vital signs, physical examination, and electrocardiogram (ECG) measurements. [Time frame: Approximately 12 months.]
• Recommended Phase 2 Dose (RP2D) [Time frame: Approximately 40 months]

Secondary outcome measures (6)

• 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]

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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.

Other protocol inclusion and exclusion criteria may apply.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 6 centers

• Sarah Cannon Research Institute at HealthONE — Denver
• The University of Chicago Medical Center - Duchossois Center for Advanced Medicine — Chicago
• University Hospitals Cleveland Medical Center — Cleveland
• University of Pennsylvania - Abramson Cancer Center — Philadelphia
• SCRI Oncology Partners — Nashville
• NEXT Oncology - Austin — Austin

China · 4 centers

• Henan Cancer Hospital — Zhengzhou
• Shanghai Pulmonary Hospital — Shanghai
• Cancer Hospital Chinese Academy of Medical Sciences — Beijing
• Sun Yat-Sen University Cancer Center — Guangzhou

Identifiers

NCT: NCT06566079 · ISM6331-101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗