Locally Advanced/Metastatic Solid TumorsPhase 1/2NCT06414460
Study of ISM3412 in Participants With Locally Advanced/Metastatic Solid Tumors
A Phase 1/2 study testing ISM3412 in people with Locally Advanced/Metastatic Solid Tumors, run by InSilico Medicine Hong Kong Limited at 10 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Locally Advanced/Metastatic Solid Tumors
- What is being tested?
- ISM3412
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 146 participants
- Where
- 10 sitesin 2 countries
- Study dates
- 25 Apr 2025to 31 Mar 2029
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female participants with age ≥18 years at the time of signing the informed consent.
- 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.
- 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.
- ECOG PS (Eastern Cooperative Oncology Group Performance Status) ≤1.
- Life expectancy of ≥12 weeks as judged by the investigator.
- Adequate organ function as determined by medical assessment.
- Capable of providing signed ICF and complying with the requirements and restrictions listed in the ICF and in this study protocol.
Who cannot join
- Prior treated with other MAT2A inhibitors and/or PRMT inhibitors.
- 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 (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.
- Toxicities of prior therapy have not resolved to Grade ≤1 or to baseline (as evaluated by NCI CTCAE version 5.0)
- History of another primary tumor that has been diagnosed or required therapy within the past 3 years.
- Previous history of, or presence of Gilbert's syndrome.
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- Previous history of myelodysplastic syndrome.
- Prior solid organ or hematopoietic stem cell transplant.
- Known active central nervous system (CNS) primary tumor or untreated CNS metastases.
- Have serious cardiovascular or cerebrovascular disease as per protocol.
- Presence of uncontrolled systemic infection as per protocol.
- 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.
Trial locations and contacts
10 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
10 sites in 2 countries
United States5 sites, 5 recruiting
- Recruiting
Sarah Cannon Research Institute at HealthONE
Denver, Colorado, 80218
- Recruiting
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030-4095
- Recruiting
Community Cancer Center North
Indianapolis, Indiana, 46250-2042
- Recruiting
SCRI Oncology Partners
Nashville, Tennessee, 37203
- Recruiting
Smilow Cancer Hospital at Yale New Haven Breast Center
New Haven, Connecticut, 06520-8028
Patricia LoRusso
China5 sites, 5 recruiting
- Recruiting
Cancer Hospital Chinese Academy of Medical Sciences
Beijing, Beijing Municipality
- Recruiting
Peking University People's Hospital
Beijing, Beijing Municipality
- Recruiting
Sun Yat-sen university cancer center
Guangzhou, Guangdong, 510030
Kai Yao
- Recruiting
Jiangsu Provincial People's Hospital
Nanjing, Jiangsu
- Recruiting
Shanghai Gobroad Cancer Hospital
Shanghai, Shanghai Municipality
About this study
Official title: A Phase 1/2, Open-Label, Multicenter, First-in-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics/Pharmacodynamics, and Preliminary Efficacy of ISM3412 in Participants With Locally Advanced/Metastatic Solid Tumors
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
- Being tested
- ISM3412
- Keywords
- Methionine adenosyltransferase 2A (MAT2A), homozygous MTAP deletion, MAT2A inhibitor, ISM3412
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ISM3412Drug
ISM3412 will be administered orally once daily.
| Study group | Role | What they receive |
|---|---|---|
| Part 1 Dose Escalation | Experimental | Patients will receive ISM3412 once daily in sequential cohorts of increasing doses. Receives: Drug: ISM3412 |
| Part 2 Dose Selection Optimization | Experimental | Participants will be randomized to receive one of the two selected dose levels of ISM3412 once daily determined by Study Review Committee. Receives: Drug: ISM3412 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of dose-limiting toxicity (DLT) events
To evaluate the safety and tolerability of ISM3412.
Measured: 31 days
Incidence and severity of adverse events (AEs)
To evaluate the safety and tolerability of ISM3412.
Measured: Approximately 30 months
Recommended phase 2 dose (RP2D)
To determine the RP2D of ISM3412.
Measured: Approximately 30 months
Secondary outcomes (7)
Maximum observed concentration (Cmax)
To assess PK of ISM3412 in plasma following a single and multiple doses of ISM3412
Measured: Approximately 30 months
Time of maximum observed concentration (Tmax)
To assess PK of ISM3412 in plasma following a single and multiple doses of ISM3412
Measured: Approximately 30 months
Area under the concentration-time curve (AUC)
To assess PK of ISM3412 in plasma following a single and multiple doses of ISM3412
Measured: Approximately 30 months
Terminal half-life (t1/2)
To assess PK of ISM3412 in plasma following a single and multiple doses of ISM3412
Measured: Approximately 30 months
Objective response rate (ORR)
To evaluate the preliminary efficacy of ISM3412 in participants with locally advanced/metastatic solid tumors.
Measured: Approximately 30 months
Best objective response (BOR)
To evaluate the preliminary efficacy of ISM3412 in participants with locally advanced/metastatic solid tumors.
Measured: Approximately 30 months
Duration of response (DoR)
To evaluate the preliminary efficacy of ISM3412 in participants with locally advanced/metastatic solid tumors.
Measured: Approximately 30 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2024
- Study start25 Apr 2025
- Primary completion31 Mar 2028 (estimated)
- Study completion31 Mar 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Locally Advanced/Metastatic Solid TumorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 146 participants (estimated)
Sponsor and investigators
- Lead sponsor
- InSilico Medicine Hong Kong Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06414460
- Sponsor's protocol ID
- ISM3412-101
- Status last verified
- Nov 2025
- First submitted
- 7 May 2024
- Last updated
- 1 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2, Open-Label, Multicenter, First-in-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics/Pharmacodynamics, and Preliminary Efficacy of ISM3412 in Participants With Locally Advanced/Metastatic Solid Tumors
- ClinicalTrials.gov ID
- NCT06414460
- Acronym / sponsor ID
- ISM3412-101
- Conditions
- Locally Advanced/Metastatic Solid Tumors
- Keywords
- Methionine adenosyltransferase 2A (MAT2A), homozygous MTAP deletion, MAT2A inhibitor, ISM3412
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 146 participants (estimated)
- Lead sponsor
- InSilico Medicine Hong Kong LimitedIndustry (pharma, biotech, devices)
- Study start
- 25 Apr 2025 (actual)
- Primary completion
- 31 Mar 2028 (estimated)
- Study completion
- 31 Mar 2029 (estimated)
- First posted
- 16 May 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Part 1 Dose Escalation | Experimental | Drug: ISM3412Patients will receive ISM3412 once daily in sequential cohorts of increasing doses. |
| Part 2 Dose Selection Optimization | Experimental | Drug: ISM3412Participants will be randomized to receive one of the two selected dose levels of ISM3412 once daily determined by Study Review Committee. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Male or female participants with age ≥18 years at the time of signing the informed consent.
- 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.
- 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.
- ECOG PS (Eastern Cooperative Oncology Group Performance Status) ≤1.
- Life expectancy of ≥12 weeks as judged by the investigator.
Key exclusion criteria (13 listed)
- Prior treated with other MAT2A inhibitors and/or PRMT inhibitors.
- 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 (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.
- Toxicities of prior therapy have not resolved to Grade ≤1 or to baseline (as evaluated by NCI CTCAE version 5.0)
- History of another primary tumor that has been diagnosed or required therapy within the past 3 years.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ISM3412ISM3412 will be administered orally once daily. | Drug | Part 1 Dose Escalation, Part 2 Dose Selection Optimization |
Primary outcome
Incidence of dose-limiting toxicity (DLT) events
Time frame: 31 days
To evaluate the safety and tolerability of ISM3412.
Incidence and severity of adverse events (AEs)
Time frame: Approximately 30 months
To evaluate the safety and tolerability of ISM3412.
Recommended phase 2 dose (RP2D)
Time frame: Approximately 30 months
To determine the RP2D of ISM3412.
7 secondary outcomes
Maximum observed concentration (Cmax)
Time frame: Approximately 30 months
Time of maximum observed concentration (Tmax)
Time frame: Approximately 30 months
Area under the concentration-time curve (AUC)
Time frame: Approximately 30 months
Terminal half-life (t1/2)
Time frame: Approximately 30 months
Objective response rate (ORR)
Time frame: Approximately 30 months
Best objective response (BOR)
Time frame: Approximately 30 months
Duration of response (DoR)
Time frame: Approximately 30 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Sep 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
10 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ISM3412 in people with Locally Advanced/Metastatic Solid Tumors, run by InSilico Medicine Hong Kong Limited at 10 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 1 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States, China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Johnny Ju (+86 021-50831718, Insilico-Clinicaltrial@insilico.ai), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of dose-limiting toxicity (DLT) events (time frame: 31 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Sep 2026.