ISM6331 for Cancer

Recruiting at 4 trial locations

Overseen By Yichen Liu

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

Trial Summary

What is the purpose of this trial?

This is a Phase 1, open-label, multicenter, FIH study to evaluate the safety, tolerability, recommended Phase 2 dose (RP2D), PK/PD, and preliminary anti-tumor activity of ISM6331 in participants with advanced or metastatic malignant mesothelioma or other solid tumors. The study consists of two parts, a dose escalation part (Part 1) and a dose selection optimization part (Part 2).

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.

How does the drug ISM6331 differ from other cancer treatments?

The drug ISM6331 may offer a unique approach by targeting the CYR61/alpha(v)beta(3) signaling pathway, which is involved in both angiogenesis (formation of new blood vessels) and breast cancer progression, potentially providing dual anti-angiogenic and anti-tumor benefits. ^{1 2 3 4 5}

Eligibility Criteria

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

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

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

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

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

Treatment Details

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).

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

The angiogenic factor CYR61 in breast cancer: molecular pathology and therapeutic perspectives. [2019]

2. Korea (South) pubmed.ncbi.nlm.nih.gov

Contributions of the alpha6 integrins to breast carcinoma survival and progression. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

High expression level of alpha 6 integrin in human breast carcinoma is correlated with reduced survival. [2004]

4. England pubmed.ncbi.nlm.nih.gov

Involvement of alpha6beta4 integrin in the mechanisms that regulate breast cancer progression. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Expression of the beta 4 integrin subunit induces monocytic differentiation of 32D/v-Abl cells. [2021]