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

NCT ID: NCT06414460

Last Updated: 2025-12-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

80 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-04-25

Study Completion Date

2029-03-31

Brief Summary

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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

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Conditions

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Locally Advanced/Metastatic Solid Tumors

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Part 1 Dose Escalation

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

Group Type EXPERIMENTAL

ISM3412

Intervention Type DRUG

ISM3412 will be administered orally once daily.

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.

Group Type EXPERIMENTAL

ISM3412

Intervention Type DRUG

ISM3412 will be administered orally once daily.

Interventions

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ISM3412

ISM3412 will be administered orally once daily.

Intervention Type DRUG

Eligibility Criteria

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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.

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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InSilico Medicine Hong Kong Limited

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Sarah Cannon Research Institute at HealthONE

Denver, Colorado, United States

Site Status RECRUITING

Smilow Cancer Hospital at Yale New Haven Breast Center

New Haven, Connecticut, United States

Site Status RECRUITING

Community Cancer Center North

Indianapolis, Indiana, United States

Site Status RECRUITING

SCRI Oncology Partners

Nashville, Tennessee, United States

Site Status RECRUITING

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status RECRUITING

Cancer Hospital Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, China

Site Status RECRUITING

Sun Yat-sen university cancer center

Guangzhou, Guangdong, China

Site Status RECRUITING

Jiangsu Provincial People's Hospital

Nanjing, Jiangsu, China

Site Status RECRUITING

Shanghai Gobroad Cancer Hospital

Shanghai, Shanghai Municipality, China

Site Status RECRUITING

Countries

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United States China

Central Contacts

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Rebecca Griffith

Role: CONTACT

+86 021-50831718

Rebecca Griffith

Role: CONTACT

+1 (254) 265-2782

Facility Contacts

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Patricia LoRusso

Role: primary

Kai Yao

Role: primary

Other Identifiers

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ISM3412-101

Identifier Type: -

Identifier Source: org_study_id

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