ISM6331 for Cancer

Recruiting at 8 trial locations

Overseen By Qinhan Chen

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: InSilico Medicine Hong Kong Limited

Must not be taking: TEAD inhibitors

Disqualifiers: CNS tumors, Severe diseases, others

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

Compensation: Varies

Number of Visits: Unknown

82 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new cancer treatment, ISM6331 (experimental treatment), to determine its safety and effects on tumors. It targets individuals with advanced or metastatic malignant mesothelioma or other solid tumors unresponsive to standard therapies. The trial consists of two parts: the first involves testing increasing doses of ISM6331, and the second selects the optimal dose for future use. Suitable candidates have mesothelioma or other solid tumors that cannot be treated with surgery and have previously undergone immune checkpoint therapy and platinum-based chemotherapy. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial requires that you stop any anti-tumor therapy at least 28 days before starting the study treatment. The protocol does not specify about other medications, so it's best to discuss with the study team.

Is there any evidence suggesting that ISM6331 is likely to be safe for humans?

Research has shown that ISM6331 has been promising in early safety checks. In lab studies conducted before human testing, ISM6331 was generally safe and did not cause serious side effects.

Now in a Phase 1 trial, this stage primarily assesses its safety for humans. While safety information is still being collected from participants, the goal is to ensure its safety and determine the correct dose. Participants in this trial will contribute to understanding how well people tolerate ISM6331 and identify any side effects that might occur at different doses. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard cancer treatments like chemotherapy or radiation, which often target both healthy and cancerous cells, ISM6331 is designed to specifically target cancer cells, potentially reducing side effects. Researchers are excited about ISM6331 because it employs a novel mechanism of action, which could lead to more effective and precise cancer treatment. Additionally, ISM6331 is administered once daily, making it a convenient option for patients compared to some existing therapies that require more frequent dosing.

What evidence suggests that ISM6331 might be an effective treatment for cancer?

Research has shown that ISM6331 produced promising results in early studies. It performed well against various cancer cell types and proved effective even at low doses in animal tests. Initial patient data, particularly from those with mesothelioma, showed positive responses, suggesting potential effectiveness for this cancer type. In this trial, participants will receive ISM6331 in different dosing regimens to optimize its effectiveness. ISM6331 may also enhance current treatments by targeting mesothelioma cells that resist other therapies. Although more research is needed, these early results offer hope for treating advanced cancers. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

Adults with advanced or metastatic malignant mesothelioma or other solid tumors who have tried at least two treatments, including immune therapy. They must be in relatively good health (ECOG ≤1), expect to live more than 12 weeks, and have proper organ function. Participants need a confirmed diagnosis and measurable disease progression after standard treatment.

Inclusion Criteria

Life expectancy of ≥12 weeks as judged by the investigator

Capable of providing signed informed consent form (ICF) and complying with the requirements and restrictions listed in the ICF and in this study protocol

I have had at least 2 treatments for mesothelioma, including immunotherapy.

Exclusion Criteria

I cannot or will not take pills due to a stomach condition.

Participation in other therapeutic clinical studies within 28 days or 5 half-lives prior to first dose of study treatment

Prior or ongoing clinically significant illness, medical condition, surgical history, physical finding, laboratory abnormality, or any other conditions that, in the investigator's opinion, would not be in the best interest of the participant; or that could alter the absorption, distribution, metabolism, or excretion of the study treatment; or impair the assessment of study result

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive ISM6331 once daily in sequential cohorts of increasing doses to evaluate safety and determine the recommended Phase 2 dose

Approximately 31 days

Daily visits for dose administration

Dose Selection Optimization

Participants receive ISM6331 once daily at selected dose levels to further evaluate safety and efficacy

Approximately 40 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Approximately 12 months

What Are the Treatments Tested in This Trial?

Interventions

• ISM6331

Trial Overview ISM6331 is being tested for safety, tolerability, optimal dosing levels, how it affects the body (PK/PD), and its ability to shrink tumors. The trial has two parts: first finding the right dose (Part 1) and then optimizing that dose (Part 2).

How Is the Trial Designed?

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

Participants will receive ISM6331 once daily at each dose level from the two dose levels recommended by Study Review Committee.

Group II: Part 1 Dose Escalation Experimental Treatment 1 Intervention

Patients will receive ISM6331 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

Integrin alpha6beta4 is primarily found in epithelial tissues and is often overexpressed in various epithelial tumors, suggesting its role in promoting tumor malignancy.

This integrin activates important signaling pathways, particularly the phosphatidylinositol 3-kinase/Akt pathway, which is crucial for regulating tumor behavior and supporting the survival and progression of mammary tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Involvement of alpha6beta4 integrin in the mechanisms that regulate breast cancer progression. Bon, G., Folgiero, V., Di Carlo, S., et al.[2018]

CYR61 is overexpressed in invasive and metastatic breast cancer cells, and its elevated levels are linked to more advanced disease, suggesting it plays a significant role in breast cancer progression.

The interaction between CYR61 and its integrin receptor alpha(v)beta(3) not only enhances breast cancer aggressiveness but also protects cancer cells from chemotherapy-induced death, indicating a potential target for dual anti-angiogenic and anti-tumor therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The angiogenic factor CYR61 in breast cancer: molecular pathology and therapeutic perspectives. Menéndez, JA., Mehmi, I., Griggs, DW., et al.[2019]

The alpha 6 beta 4 integrin, when expressed in transformed cells, reduces tumor aggressiveness and inhibits cell proliferation by inducing monocytic differentiation, suggesting a potential therapeutic role in cancer treatment.

This integrin's effects are linked to the activation of the c-Abl kinase and accumulation of the p73 protein, indicating a mechanism by which it promotes growth arrest and differentiation in tumor cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expression of the beta 4 integrin subunit induces monocytic differentiation of 32D/v-Abl cells. Morena, A., Riccioni, S., Marchetti, A., et al.[2021]

Alpha6 integrins (alpha6beta1 and alpha6beta4) play a crucial role in the survival of breast carcinoma cells, particularly under stressful conditions found in the tumor microenvironment.

These integrins regulate the expression of vascular endothelial growth factor (VEGF), which breast carcinoma cells use to enhance their survival through autocrine signaling.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Contributions of the alpha6 integrins to breast carcinoma survival and progression. Chung, J., Mercurio, AM.[2021]

In a study of 119 women with invasive breast carcinomas, 50% of the tumors expressed alpha 6 integrin, and this expression was linked to shorter survival times, suggesting its role in cancer progression.

Patients with tumors lacking alpha 6 integrin expression had a better prognosis, indicating that measuring alpha 6 integrin levels could be a valuable prognostic marker for breast cancer outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High expression level of alpha 6 integrin in human breast carcinoma is correlated with reduced survival. Friedrichs, K., Ruiz, P., Franke, F., et al.[2004]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06566079

NCT06566079 | Study of ISM6331 in Participants With ... Pharmacokinetics (PK) parameters of ISM6331 after dose of ISM6331 will be assessed. Approximately 12 months. Objective response rate (ORR). Efficacy assessments ...

2. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/529955

Study of ISM6331 in Participants With Advanced/Metastatic ... This is a Phase 1, open-label, multicenter, FIH study to evaluate the safety, tolerability, recommended Phase 2 dose (RP2D), PK/PD, and preliminary ...

3. news-medical.net news-medical.net/news/20250122/Insilico-Medicine-doses-first-patient-in-Phase-I-Trial-of-ISM6331-for-mesothelioma.aspx

Insilico Medicine doses first patient in Phase I Trial of ... In preclinical studies, ISM6331 demonstrated broad anti-tumor efficacy in multiple cell lines, potent activity at low doses in animal models, ...

4. mesotheliomahope.com mesotheliomahope.com/blog/first-patient-dosed-in-fda-ism6331-clinical-trial/

First Mesothelioma Patient Dosed With ISM6331 in Clinical ... Adding ISM6331 to treatment plans could possibly kill more mesothelioma cells or help patients if their cancer doesn't respond to other therapies. ISM6331 ...

5. oncologypipeline.com oncologypipeline.com/apexonco/insilico-still-feels-need-tead

Insilico still feels the need for TEAD | ApexOnco Early results showed 7 responses among 69 patients; most of these were in mesothelioma patients. Ikena's flop doesn't seem to have put other ...

6. aacrjournals.org aacrjournals.org/cancerres/article/84/6_Supplement/1656/736063/Abstract-1656-ISM6331-a-novel-and-potent-pan-TEAD

Abstract 1656: ISM6331, a novel and potent pan-TEAD ... ISM6331, a novel and potent pan-TEAD inhibitor, exhibits strong anti-tumor activity in preclinical models of Hippo pathway-dysregulated cancers.

7. drugtargetreview.com drugtargetreview.com/article/110203/game-changing-pan-tead-inhibitor-for-solid-tumours/

Game-changing pan-TEAD inhibitor for solid tumours Among these, ISM6331 emerged as the leading compound, exhibiting remarkable efficacy at low doses and demonstrating a favourable safety profile ...

8. linkedin.com linkedin.com/posts/zhavoronkov_the-hippo-pathway-is-biologys-critical-brake-activity-7354495690913337347-_pf5

Insilico Medicine's ISM6331: A Pan-TEAD Inhibitor for ... ... ISM 6331 collapses the entire oncogenic transcription complex. Preclinical data confirms its pan teed action disrupts tumor survival signals ...