Recruiting
Phase 1
Phase 2

ISM3412

Sponsor:

InSilico Medicine Hong Kong Limited

Code:

NCT06414460

Conditions

Locally Advanced/Metastatic Solid Tumors

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

ISM3412

Study Details

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.

Conditions

Locally Advanced/Metastatic Solid Tumors

Study ID

NCT06414460

Start date

Apr 25, 2025

Status verified date

Nov, 2025

Completion date

Mar 31, 2029

Anticipated

Primary completion date

Mar 31, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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. ECOG PS (Eastern Cooperative Oncology Group Performance Status) ≤1.
5. Life expectancy of ≥12 weeks as judged by the investigator.
6. Adequate organ function as determined by medical assessment.
7. Capable of providing signed ICF and complying with the requirements and restrictions listed in the ICF and in this study protocol.

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.

Study Design

Enrollment

146 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Part 1 Dose Escalation

Patients will receive ISM3412 once daily in sequential cohorts of increasing doses.

experimental: Part 2 Dose Selection Optimization

Participants will be randomized to receive one of the two selected dose levels of ISM3412 once daily determined by Study Review Committee.

Interventions

ISM3412

ISM3412 will be administered orally once daily.

Primary outcome measure

  • Incidence of dose-limiting toxicity (DLT) events [ Time Frame: 31 days ]
  • Incidence and severity of adverse events (AEs) [ Time Frame: Approximately 30 months ]
  • Recommended phase 2 dose (RP2D) [ Time Frame: Approximately 30 months ]

Central Contacts and Locations

Locations

Sarah Cannon Research Institute at HealthONE

Recruiting

Denver, Colorado, United States, 80218

Smilow Cancer Hospital at Yale New Haven Breast Center

Recruiting

New Haven, Connecticut, United States, 06520-8028

Community Cancer Center North

Recruiting

Indianapolis, Indiana, United States, 46250-2042

SCRI Oncology Partners

Recruiting

Nashville, Tennessee, United States, 37203

The University of Texas MD Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030-4095

More Information

Sponsor

InSilico Medicine Hong Kong Limited

Last update posted

Sep 1, 2026

Last verified

Nov, 2025

Keywords

  • Methionine adenosyltransferase 2A (MAT2A)
  • homozygous MTAP deletion
  • MAT2A inhibitor
  • ISM3412

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by InSilico Medicine Hong Kong Limited on 2026-09-01.