Study of ISM3412 in Participants With Locally Advanced/Metastatic Solid Tumors

Phase 1

Not yet recruiting

• Conditions: Locally Advanced/Metastatic Solid Tumors
• Interventions: Drug: ISM3412

• Registration Number: NCT06414460
• Lead Sponsor: InSilico Medicine Hong Kong Limited

Brief Summary

The study has consists of two parts, a dose escalation part (Part 1) and a dose selection optimization part (Part 2). The primary objectives of this study are to evaluate the safety and tolerability of ISM3412 in participants with locally advanced/metastatic solid tumors, and to determine the RP2D of ISM3412.

Detailed Description

Not available

Basic Information
|
Recruitment & Eligibility
|
Study & Design

Study Timeline

• Status Verified: 2024-05
• Study First Submitted: 2024-05-07
• Study First Submitted QC: 2024-05-09
• Last Update Submitted: 2024-05-14
• Study First Posted: 2024-05-16
• Last Update Posted: 2024-05-16
• Study Start: 2025-03-01
• Primary Completion: 2028-03-31
• Study Completion: 2029-03-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

1. Male or female participants with age ≥18 years at the time of signing the informed consent.
2. Histologically confirmed unresectable locally advanced or metastatic solid tumors with confirmed homozygous MTAP deletion, who have disease progression after standard therapy, intolerable to standard therapy, or for whom no standard therapy exists.
3. Have measurable or evaluable lesions in Part 1 and at least one measurable target lesion in Part 2 as defined by Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
4. Participants must provide a documentary evidence of homozygous MTAP deletion; or provide archival formalin-fixed paraffin-embedded (FFPE) tumor tissue blocks or at least 15 FFPE tumor tissue slides, or perform tumor tissue biopsies for a confirmatory genetic test indicating homozygous MTAP deletion.
5. ECOG PS (Eastern Cooperative Oncology Group Performance Status) ≤1.
6. Life expectancy of ≥12 weeks as judged by the investigator.
7. Adequate organ function as determined by medical assessment.
8. Capable of providing signed ICF and complying with the requirements and restrictions listed in the ICF and in this study protocol.

Read More

Exclusion Criteria

1. Prior treated with other MAT2A inhibitors and/or PRMT inhibitors.
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 (chemotherapy, immunotherapy, hormonal therapy, targeted therapy, biologic therapy, or other anti-tumor therapy, except for hormones for hypothyroidism or estrogen replacement therapy, anti-estrogen analogues, agonists required to suppress serum testosterone levels) within 28 days or 5 half-lives, whichever is shorter prior to first dose of study treatment.
4. Toxicities of prior therapy have not resolved to Grade ≤1 or to baseline (as evaluated by NCI CTCAE version 5.0)
5. History of another primary tumor that has been diagnosed or required therapy within the past 3 years.
6. Previous history of, or presence of Gilbert's syndrome.
7. Previous history of myelodysplastic syndrome.
8. Prior solid organ or hematopoietic stem cell transplant.
9. Known active central nervous system (CNS) primary tumor or untreated CNS metastases.
10. Have serious cardiovascular or cerebrovascular disease as per protocol.
11. Presence of uncontrolled systemic infection as per protocol.
12. Unwillingness or unable to comply with the requirements of oral drug administration, or presence of a gastro-intestinal condition.

Other protocol inclusion and exclusion criteria may apply.

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Part 2 Dose Selection Optimization	ISM3412	Participants will be randomized to receive one of the two selected dose levels of ISM3412 once daily determined by Study Review Committee.
Part 1 Dose Escalation	ISM3412	Patients will receive ISM3412 once daily in sequential cohorts of increasing doses.

Primary Outcome Measures

Name	Time	Method
Incidence and severity of adverse events (AEs)	Approximately 30 months	To evaluate the safety and tolerability of ISM3412.
Recommended phase 2 dose (RP2D)	Approximately 30 months	To determine the RP2D of ISM3412.
Incidence of dose-limiting toxicity (DLT) events	31 days	To evaluate the safety and tolerability of ISM3412.

Secondary Outcome Measures

Name	Time	Method
Terminal half-life (t1/2)	Approximately 30 months	To assess PK of ISM3412 in plasma following a single and multiple doses of ISM3412
Best objective response (BOR)	Approximately 30 months	To evaluate the preliminary efficacy of ISM3412 in participants with locally advanced/metastatic solid tumors.
Objective response rate (ORR)	Approximately 30 months	To evaluate the preliminary efficacy of ISM3412 in participants with locally advanced/metastatic solid tumors.
Maximum observed concentration (Cmax)	Approximately 30 months	To assess PK of ISM3412 in plasma following a single and multiple doses of ISM3412
Time of maximum observed concentration (Tmax)	Approximately 30 months	To assess PK of ISM3412 in plasma following a single and multiple doses of ISM3412
Area under the concentration-time curve (AUC)	Approximately 30 months	To assess PK of ISM3412 in plasma following a single and multiple doses of ISM3412
Duration of response (DoR)	Approximately 30 months	To evaluate the preliminary efficacy of ISM3412 in participants with locally advanced/metastatic solid tumors.