ISM3412 for Cancer

Recruiting at 6 trial locations

Overseen By Rebecca Griffith

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: InSilico Medicine Hong Kong Limited

Must not be taking: MAT2A inhibitors, PRMT inhibitors

Disqualifiers: Other tumors, CNS tumors, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called ISM3412, a potential drug for individuals with advanced solid tumors—cancers that have spread and cannot be surgically removed. The study aims to assess the safety and tolerability of ISM3412 and determine the best dose for future research. Participants will receive either increasing doses or one of two optimal doses of ISM3412. This trial may suit those with advanced cancer featuring a specific genetic change, known as homozygous MTAP deletion, who have not responded to standard treatments. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in humans.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have had anti-tumor therapy within 28 days before starting the trial, and you cannot participate in other clinical studies during this time.

Is there any evidence suggesting that ISM3412 is likely to be safe for humans?

Research has shown that ISM3412 appears safe based on early studies. Preclinical tests found that the treatment was well-tolerated, with no serious side effects. Importantly, it caused no significant harm to the liver or bile system, indicating a positive safety profile.

The current study is in the first phase of human testing, focusing on the treatment's safety and tolerability. This phase is crucial for identifying any potential side effects at various doses. While detailed results from human testing are not yet available, early studies provide a hopeful outlook on the treatment's safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for cancer?

Researchers are excited about ISM3412 because it offers a fresh approach to cancer treatment. Unlike many standard treatments that target cancer cells in a general way, ISM3412 is designed to be more precise, potentially increasing its effectiveness while reducing side effects. This treatment involves an innovative mechanism that targets specific pathways in cancer cells, making it distinct from traditional chemotherapy or radiation. By focusing on these unique pathways, ISM3412 could offer new hope for patients whose cancers are resistant to current therapies.

What evidence suggests that ISM3412 might be an effective treatment for cancer?

Research has shown that ISM3412 could be a promising treatment for solid tumors. Early studies found it to be safe, suggesting it might offer a safer option for patients. The drug blocks an enzyme that cancer cells need to grow, potentially slowing or stopping tumor growth. Although human studies have provided limited information, these early results offer hope that ISM3412 could be effective against advanced cancers. Participants in this trial will receive ISM3412 in different dosing regimens to further evaluate its safety and effectiveness. ^{1 3 5 6 7}

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors that can't be surgically removed, have worsened after standard treatment, or have no standard treatment available. Participants must show evidence of a specific genetic change (MTAP deletion) in their tumor and meet health and safety criteria.

Inclusion Criteria

I am fully active and can carry on all pre-disease activities without restriction.

I can sign the consent form and follow the study's requirements.

My doctor believes I have at least 12 weeks to live.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive ISM3412 once daily in sequential cohorts of increasing doses to evaluate safety and tolerability

31 days

Dose Selection Optimization

Participants are randomized to receive one of the two selected dose levels of ISM3412 once daily

Approximately 30 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ISM3412

Trial Overview The study tests ISM3412's safety and tolerability in two parts: finding the highest dose patients can take without serious side effects (Part 1), then optimizing the best dose to use (Part 2). It aims to find the right dosage for future studies.

How Is the Trial Designed?

Group I: Part 2 Dose Selection Optimization Experimental Treatment 1 Intervention

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

Group II: Part 1 Dose Escalation Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

InSilico Medicine Hong Kong Limited

Lead Sponsor

Trials

9

Recruited

1,100+

Published Research Related to This Trial

Immune checkpoint inhibitors (ICIs) can lead to immune-related adverse events (irAEs) due to their mechanism of action, necessitating a multidisciplinary approach for effective patient management, as highlighted by 30 real-world pharmacovigilance studies.

These studies have provided valuable insights into the patterns, kinetics, and fatality rates of various irAEs, emphasizing the need for oncologists to understand both the strengths and limitations of this data for better patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lessons to be Learnt from Real-World Studies on Immune-Related Adverse Events with Checkpoint Inhibitors: A Clinical Perspective from Pharmacovigilance. Raschi, E., Gatti, M., Gelsomino, F., et al.[2021]

In a study of 2212 patients with advanced non-small cell lung cancer, those over 65 years old showed similar safety and efficacy outcomes when treated with bevacizumab (Avastin) combined with standard chemotherapy, compared to younger patients.

Elderly patients had comparable overall survival (14.6 months) and time to disease progression (8.2 months) as younger patients, with no significant increase in adverse events, indicating that bevacizumab is a safe and effective treatment option for older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of first-line bevacizumab plus chemotherapy in elderly patients with advanced or recurrent nonsquamous non-small cell lung cancer: safety of avastin in lung trial (MO19390). Laskin, J., Crinò, L., Felip, E., et al.[2015]

Novel clinical trial designs like umbrella, basket, and adaptive enrichment strategies are being developed to speed up drug testing in oncology, allowing for more precise targeting of therapies to specific patient groups.

These designs require advanced statistical methods and collaboration across multiple disciplines, highlighting the need for improved infrastructure and data technologies to effectively implement and interpret trial results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improving Clinical Trial Efficiency: Thinking outside the Box. Mandrekar, SJ., Dahlberg, SE., Simon, R.[2022]

In a prospective study involving patients with refractory malignancies, personalized treatment using combination therapies was feasible, with 49% of patients receiving tailored multidrug regimens.

Higher 'matching scores' from targeting more molecular alterations were associated with significantly better disease control and longer progression-free and overall survival rates, suggesting that combination therapies may enhance outcomes compared to traditional single-drug approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular profiling of cancer patients enables personalized combination therapy: the I-PREDICT study. Sicklick, JK., Kato, S., Okamura, R., et al.[2021]

The developed gene expression sensitivity profiles can accurately predict patient responses to PARP inhibitors, outperforming traditional biomarkers like BRCA1/2 mutation status in identifying sensitive cancer cell lines and patient-derived tumors.

These drug sensitivity signatures not only predict responses to existing therapies but also help identify new drug combinations that could enhance treatment efficacy, potentially improving patient outcomes in cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved prediction of PARP inhibitor response and identification of synergizing agents through use of a novel gene expression signature generation algorithm. McGrail, DJ., Lin, CC., Garnett, J., et al.[2020]

Recent advancements in the treatment of metastatic breast cancer emphasize the importance of using patient and tumor-specific biomarkers to tailor individualized therapies, enhancing the potential for more effective treatments.

The PRAEGNANT study network is addressing the challenges of personalized medicine by creating a professional infrastructure that supports the integration of molecular tumor data into clinical studies, while still prioritizing patient quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biomarkers in Patients with Metastatic Breast Cancer and the PRAEGNANT Study Network. Fasching, PA., Brucker, SY., Fehm, TN., et al.[2022]

In a study of 226 breast cancer patients, low expression of the protein p27kip1 was linked to poorer overall survival rates specifically in those receiving taxane-based chemotherapy, suggesting it could serve as a prognostic indicator.

While low p57kip2 expression was associated with negative progesterone receptor status, it did not show a significant impact on patient outcomes, highlighting the particular importance of p27kip1 in predicting responses to taxane treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Loss of p27kip1 expression is associated with poor prognosis in patients with taxane-treated breast cancer. Kim, GJ., Kim, DH., Min, KW., et al.[2018]

A large-scale analysis of 16,196 serious adverse drug reaction reports identified 36 potential safety signals associated with ibrutinib, including ischemic heart diseases and fractures, highlighting the need for careful patient monitoring.

The study found that over half of the reports resulted in hospitalization, indicating that while ibrutinib is a standard treatment for B-cell malignancies, its safety profile requires further investigation to confirm these findings in broader populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Profile of Ibrutinib: An Analysis of the WHO Pharmacovigilance Database. Allouchery, M., Tomowiak, C., Lombard, T., et al.[2021]

The combination of the PI3K inhibitor pictilisib and the aromatase inhibitor anastrozole effectively suppresses the growth of luminal B breast cancer cells, indicating a potential therapeutic strategy for this subtype of breast cancer.

This study highlights the efficacy of targeting multiple pathways in breast cancer treatment, suggesting that combining these two drugs may enhance treatment outcomes for patients with luminal B breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pictilisib Plus Anastrozole Reduces Proliferation in ER+ Breast Cancer. [2018]

In a phase IB trial involving 50 patients with advanced solid tumors, the combination of LY2780301 and gemcitabine demonstrated manageable toxicity, with the maximum tolerated dose established at 500 mg of LY2780301 and 750 mg/m2 of gemcitabine.

The treatment showed promising antitumor activity, with a disease control rate of 74% at cycle 2 and partial responses in 5% of patients, particularly in those with alterations in the PI3K/AKT/mTOR signaling pathway.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, tolerability and antitumour activity of LY2780301 (p70S6K/AKT inhibitor) in combination with gemcitabine in molecularly selected patients with advanced or metastatic cancer: a phase IB dose escalation study. Angevin, E., Cassier, PA., Italiano, A., et al.[2022]

In a phase I trial involving 120 patients with solid tumors, apitolisib (GDC-0980) was found to be reasonably tolerated at a dose of 30 mg, with the recommended phase 2 dose (RP2D) established at 40 mg once daily, despite some severe side effects like hyperglycemia and pneumonitis.

The treatment showed promising preliminary antitumor activity, with 10 confirmed partial responses in various cancer types, and significant modulation of target pathways was observed, indicating its potential effectiveness as a cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Study of Apitolisib (GDC-0980), Dual Phosphatidylinositol-3-Kinase and Mammalian Target of Rapamycin Kinase Inhibitor, in Patients with Advanced Solid Tumors. Dolly, SO., Wagner, AJ., Bendell, JC., et al.[2022]

M2698, an oral dual inhibitor targeting the p70S6K/AKT pathway, was well tolerated in 101 patients with advanced cancer, showing manageable side effects primarily related to gastrointestinal issues and fatigue.

In patients with advanced breast cancer resistant to standard therapies, M2698 demonstrated some antitumor activity, with two patients achieving partial responses when combined with trastuzumab or tamoxifen, indicating potential effectiveness in overcoming treatment resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 study of M2698, a p70S6K/AKT dual inhibitor, in patients with advanced cancer. Tsimberidou, AM., Shaw, JV., Juric, D., et al.[2022]

A meta-analysis of 53 Phase II/III/IV trials involving nearly 20,000 patients revealed that molecular target anticancer drugs significantly increase the risk of serious adverse events (SAEs) by 57% and fatal adverse events (FAEs) by 51% compared to placebo.

The overall incidence rates for SAEs and FAEs were found to be 26.9% and 2.3%, respectively, highlighting the need for careful monitoring and preventive measures for patients receiving these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of serious adverse event and fatal adverse event with molecular target anticancer drugs in cancer patients: A meta-analysis. Wang, Z., Yang, X., Wang, J., et al.[2020]

A total of 3120 adverse event cases related to avapritinib were reported to the FDA, with 44% occurring within the first 30 days of treatment, highlighting the importance of monitoring patients closely during this period.

The study found that elderly male patients are at a higher risk for serious adverse events, indicating that clinicians should exercise caution when prescribing avapritinib to this demographic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A post-marketing pharmacovigilance study of avapritinib: Adverse event data mining and analysis based on the United States Food and Drug Administration Adverse Event Reporting System database. Rong, L., Xie, M., Jiang, M., et al.[2023]

In a study of 1,000 patients who underwent FoundationOne CDx™ testing, 652 had actionable mutations, and 38 received targeted therapies, showing a disease control rate of 41.2% with some patients achieving partial responses.

The median progression-free survival was 2.7 months and median overall survival was 9.9 months, indicating that while targeted therapies based on genetic alterations can be beneficial, further research is needed to fully understand their efficacy in community oncology settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Precision Medicine on Clinical Outcomes: A Single-Institution Retrospective Study. Quinn, R., Patel, R., Sison, C., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06414460

Study of ISM3412 in Participants With Locally Advanced ... To evaluate the preliminary efficacy of ISM3412 in participants with locally advanced/metastatic solid tumors. Approximately 30 months. Best objective ...

2. firstwordpharma.com firstwordpharma.com/story/5976788

Insilico Medicine completes first-in-patient dosing of ... “In preclinical studies, ISM3412 has demonstrated a promising safety profile, highlighting its potential to improve treatment options for ...

3. withpower.com withpower.com/trial/phase-1-neoplasms-2-2025-80782

ISM3412 for Cancer · Recruiting Participants for Phase ... In a study of 2212 patients with advanced non-small cell lung cancer, those over 65 years old showed similar safety and efficacy outcomes when treated with ...

4. ddw-online.com ddw-online.com/first-patient-receives-novel-mat2a-inhibitor-for-solid-tumours-35546-202507/

First patient receives novel MAT2A inhibitor for solid tumours “In preclinical studies, ISM3412 has demonstrated a promising safety profile, highlighting its potential to improve treatment options for ...

5. news-medical.net news-medical.net/news/20240425/Insilico-Medicines-AI-designed-drug-ISM3412-receives-FDA-IND-approval.aspx

Insilico Medicine's AI-designed drug ISM3412 receives ... Multicenter phase 1/2 study of onatasertib, a dual TORC1/2 inhibitor, combined with the PD-1 antibody toripalimab in advanced solid tumors.

6. news-medical.net news-medical.net/news/20250627/Insilico-Medicine-begins-clinical-trial-for-AI-designed-cancer-drug-ISM3412.aspx

Insilico Medicine begins clinical trial for AI-designed cancer ... "In preclinical studies, ISM3412 has demonstrated a promising safety profile, highlighting its potential to improve treatment options for ...

7. aacrjournals.org aacrjournals.org/cancerres/article/83/7_Supplement/503/722655/Abstract-503-ISM3412-a-novel-and-selective-MAT2A

Abstract 503: ISM3412, a novel and selective MAT2A inhibitor ... In vivo PK data revealed low clearance and high oral-bioavailability. Further, it was well tolerated with no significant hepatobiliary toxicity.