Study of ISM6331 in Participants With Advanced/Metastatic Mesothelioma or Other Advanced Solid Tumors
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorInSilico Medicine Hong Kong Limited
About this trial
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).
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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.
Trial design
Design model
Sequential
Treatments tested in this trial
ISM6331
DrugDosage form: Capsule for oral administration. Frequency of administration: Once daily overall of treatment.
Treatment groups
160 Participants
are divided into 2 treatment groupsGroup A: Part 1 Dose EscalationExperimental treatment 1 intervention
Group B: Part 2 Dose Selection OptimizationExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
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).
Time frame
Day 1 up to Day 312
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 \[NCI CTCAE v5.0\]
Time frame
Approximately 12 months.3
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.
Time frame
Approximately 12 months.4
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.
Time frame
Approximately 40 monthsSecondary outcomes
1
Maximum observed concentration (Cmax)
Pharmacokinetics (PK) parameters of ISM6331 after dose of ISM6331 will be assessed.
Time frame
Approximately 12 months2
Area under the concentration-time curve (AUC)
Pharmacokinetics (PK) parameters of ISM6331 after dose of ISM6331 will be assessed.
Time frame
Approximately 12 months3
Terminal half-life (t1/2)
Pharmacokinetics (PK) parameters of ISM6331 after dose of ISM6331 will be assessed.
Time frame
Approximately 12 months4
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.
Time frame
Approximately 12 monthsSponsors and contacts
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Source ClinicalTrials.gov