MT-4561 for Cancer

Recruiting at 1 trial location

Overseen By Clinical Trials Information Desk, to prevent miscommunication,

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Mitsubishi Tanabe Pharma America Inc.

Must not be taking: QT prolonging drugs

Disqualifiers: Active brain metastases, unresolved toxicity, others

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

Compensation: Varies

Number of Visits: Unknown

27 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking any prior systemic anticancer therapy at least 4 weeks before starting the study drug, or 5 half-lives of the drug, whichever is shorter. Additionally, you must not have taken drugs that can prolong the QT interval within 14 days or 5 half-lives before starting the study drug.

What data supports the effectiveness of the drug MT-4561 for cancer?

Research on similar treatments shows that combining chemotherapy with certain antibodies can improve survival rates in lung cancer. Additionally, using mTOR inhibitors like temsirolimus has shown promise in treating mesothelioma, suggesting potential benefits for MT-4561 if it has similar properties. ^{1 2 3 4 5}

What safety data exists for MT-4561 or similar treatments in humans?

PD-1/PD-L1 inhibitors, which may be similar to MT-4561, have been studied for safety in various cancers. Common side effects include fatigue and febrile neutropenia (a condition with fever and low white blood cells), but the overall safety profile is considered acceptable in the studies reviewed. ^{6 7 8 9 10}

How does the drug MT-4561 differ from other cancer treatments?

MT-4561, also known as taurolidine, is unique because it is a novel antineoplastic agent (a drug that fights tumors) being studied for its effectiveness against malignant mesothelioma, a cancer with poor responses to current treatments. This sets it apart from existing therapies that have limited success in treating this aggressive cancer. ^{8 11 12 13 14}

What is the purpose of this trial?

This is a First In Human (FIH), multicenter, open-label, Phase I/II study to evaluate safety, tolerability, Pharmacokinetics (PK), pharmacodynamics, and efficacy of MT-4561 in patients with advanced solid tumors. This study will be conducted in 3 parts. Part 1 is aimed at evaluating safety, tolerability, PK and pharmacodynamics of MT-4561 and determining the Maximum Tolerated Dose (MTD) using the Bayesian Optimal Interval (BOIN) design. The study details and doses of Part 2 (dose-optimization) and Part 3 (Drug-Drug Interaction) will be available after review of applicable Part 1 results.

Research Team

Head of Medical Science

Principal Investigator

Mitsubishi Tanabe Pharma America Inc.

Eligibility Criteria

This trial is for patients with various advanced solid tumors who are seeking new treatment options. Participants must meet specific health criteria, which will be detailed in the study's inclusion and exclusion sections.

Inclusion Criteria

Life expectancy of at least 3 months

I have at least one tumor that can be measured and biopsied.

My bone marrow is working well.

Exclusion Criteria

I have no lasting side effects from cancer treatment, except for hair loss.

QT interval corrected for heart rate using Fridericia's correction (QTcF) > 470 msec at screening

I have active brain or spinal cord cancer spread.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-escalation

Participants receive intravenous infusion of MT-4561 once every week in a 28-day cycle to evaluate safety, tolerability, PK, and pharmacodynamics and determine the Maximum Tolerated Dose (MTD)

28 days per cycle

Weekly visits for infusion

Dose-optimization

Further evaluation of MT-4561 dosing based on results from Part 1

Not specified

Drug-Drug Interaction

Evaluation of the effect of MT-4561 on the pharmacokinetics of oral Midazolam

Not specified

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 days after last dose

Treatment Details

Interventions

• MT-4561

Trial Overview MT-4561, a new potential cancer therapy, is being tested across three parts: assessing safety and finding the highest dose patients can tolerate (Part 1), optimizing dosage (Part 2), and studying drug interactions (Part 3).

Participant Groups

Group I: Part 1 (Dose-escalation) Experimental Treatment 1 Intervention

Intravenous (IV) infusion of MT-4561 once every week in 28-day cycle, until disease progression or discontinuation criteria are met.

Who Is Running the Clinical Trial?

Mitsubishi Tanabe Pharma America Inc.

Lead Sponsor

Trials

27

Recruited

3,300+

Findings from Research

Adjuvant therapy with PD-1/PD-L1 inhibitors significantly improves overall survival (OS) and disease-free survival (DFS) in cancer patients, based on a meta-analysis of six randomized controlled trials involving 4,436 participants.

While these treatments offer substantial survival benefits, they are also associated with a higher risk of severe treatment-related adverse events (≥ grade 3), indicating a need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of adjuvant therapy with PD‑1/PD‑L1 inhibitors in cancer. Mo, DC., Liang, ZY., Chen, L., et al.[2022]

In a meta-analysis of 4413 patients from 8 randomized controlled trials, PD-1/PD-L1 inhibitors showed a significantly lower risk of all-grade adverse events (66.20% vs. 86.08%) and high-grade adverse events (14.26% vs. 43.53%) compared to chemotherapy, indicating a better safety profile.

While PD-1/PD-L1 inhibitors are generally safer, they are associated with a unique set of immune-related adverse events (irAEs) that can be severe, such as pneumonitis and thyroid dysfunction, which clinicians need to monitor closely to manage patient quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of PD-1/PD-L1 inhibitors in the treatment of non-small cell lung cancer: a meta-analysis of randomized controlled trials. Luo, W., Wang, Z., Tian, P., et al.[2021]

Neoadjuvant anti-PD-1/PD-L1 therapy showed promising efficacy, with a complete response rate of 56.9% in triple-negative breast cancer and a major response rate of 47.1% in lung cancer, based on a meta-analysis of 20 studies involving 828 patients.

The therapy was generally safe, with fatigue being the most common adverse event (27.2%), while febrile neutropenia was the most frequent high-grade adverse event (8.4%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical benefit of neoadjuvant anti-PD-1/PD-L1 utilization among different tumors. Li, Z., Wu, X., Zhao, Y., et al.[2021]

References

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

A Real-World Analysis of the Use of Systemic Therapy in Malignant Pleural Mesothelioma and the Differential Impacts on Overall Survival by Practice Pattern. [2022]

2. Ireland pubmed.ncbi.nlm.nih.gov

Real-life treatment practice for malignant pleural mesothelioma in Belgium. [2020]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Anti-PD-1 Monoclonal Antibodies (mAbs) Are Superior to Anti-PD-L1 mAbs When Combined with Chemotherapy in First-Line Treatment for Metastatic Non-Small Cell Lung Cancer (mNSCLC): A Network Meta-Analysis. [2023]

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

Coactivation of receptor tyrosine kinases in malignant mesothelioma as a rationale for combination targeted therapy. [2021]

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

Temsirolimus inhibits malignant pleural mesothelioma growth in vitro and in vivo: synergism with chemotherapy. [2014]

6. Greece pubmed.ncbi.nlm.nih.gov

Efficacy and safety of adjuvant therapy with PD‑1/PD‑L1 inhibitors in cancer. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Safety and tolerability of PD-1/PD-L1 inhibitors in the treatment of non-small cell lung cancer: a meta-analysis of randomized controlled trials. [2021]

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

The effects of taurolidine, a novel antineoplastic agent, on human malignant mesothelioma. [2013]

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

Effectiveness and safety of PD-1/PD-L1 inhibitors in the treatment of solid tumors: a systematic review and meta-analysis. [2022]

10. China pubmed.ncbi.nlm.nih.gov

Clinical benefit of neoadjuvant anti-PD-1/PD-L1 utilization among different tumors. [2021]

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

Temporal and spatial heterogeneity of programmed cell death 1-Ligand 1 expression in malignant mesothelioma. [2021]

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

An orthotopic implantation mouse model of human malignant pleural mesothelioma for in vivo photon counting analysis and evaluation of the effect of S-1 therapy. [2021]

13. Australia pubmed.ncbi.nlm.nih.gov

SU6668, a multiple tyrosine kinase inhibitor, inhibits progression of human malignant pleural mesothelioma in an orthotopic model. [2021]

14. Germany pubmed.ncbi.nlm.nih.gov

The therapeutic efficacy of S-1 against orthotopically implanted human pleural mesothelioma cells in severe combined immunodeficient mice. [2021]