Mts105 for Advanced Hepatocellular Carcinoma

NCT ID: NCT06689540

Last Updated: 2024-12-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

14 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-11-18

Study Completion Date

2026-12-31

Brief Summary

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This is the first-in-human trial of MTS105 (mRNA-LNP). The goal of this clinical trial is to evaluate the safety, tolerability of intravenous injection of MTS105 in advanced hepatocellular carcinoma.

Detailed Description

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MTS105 is an mRNA-LNP combination. Once the mRNA is delivered to the liver via lipid nanoparticles (LNP), it translates into a therapeutic bispecific T-cell engager designed to activate T cells to target and destroy liver cancer cells.

MTS105 is anticipated to offer liver-targeted delivery, specific binding to hepatocellular carcinoma cells, a broad therapeutic window, and potent anti-tumor effects.

Conditions

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Liver Cancer, Adult Metastatic Liver Cancers HCC - Hepatocellular Carcinoma Hepatocellular Carcinoma (HCC)

Keywords

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hcc mts105 metis mRNA LNP

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Bayesian Optimal Interval (BOIN) Design
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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dose level #1

Starting dose, 0.05 ug/kg

Group Type EXPERIMENTAL

MTS105

Intervention Type BIOLOGICAL

MTS105 is a combination of mRNA, which encodes a therapeutic protein, and its delivery vehicle, a lipid nanoparticle (LNP). The starting dose is estimated based on the Minimal Anticipated Biological Effect Level (MABEL) derived from non-clinical studies.

A starting dose of 0.05 μg/kg was proposed for this study; following dose strength for escalation are: 0.5 μg/kg, 3.0 μg/kg, 15 μg/kg, 30 μg/kg, 45 μg/kg.

dose level #2

dose escalation, 0.5 ug/kg

Group Type EXPERIMENTAL

MTS105

Intervention Type BIOLOGICAL

MTS105 is a combination of mRNA, which encodes a therapeutic protein, and its delivery vehicle, a lipid nanoparticle (LNP). The starting dose is estimated based on the Minimal Anticipated Biological Effect Level (MABEL) derived from non-clinical studies.

A starting dose of 0.05 μg/kg was proposed for this study; following dose strength for escalation are: 0.5 μg/kg, 3.0 μg/kg, 15 μg/kg, 30 μg/kg, 45 μg/kg.

dose level #3

dose escalation, 3.0 ug/kg

Group Type EXPERIMENTAL

MTS105

Intervention Type BIOLOGICAL

MTS105 is a combination of mRNA, which encodes a therapeutic protein, and its delivery vehicle, a lipid nanoparticle (LNP). The starting dose is estimated based on the Minimal Anticipated Biological Effect Level (MABEL) derived from non-clinical studies.

A starting dose of 0.05 μg/kg was proposed for this study; following dose strength for escalation are: 0.5 μg/kg, 3.0 μg/kg, 15 μg/kg, 30 μg/kg, 45 μg/kg.

dose level #4

dose escalation, 15.0 ug/kg

Group Type EXPERIMENTAL

MTS105

Intervention Type BIOLOGICAL

MTS105 is a combination of mRNA, which encodes a therapeutic protein, and its delivery vehicle, a lipid nanoparticle (LNP). The starting dose is estimated based on the Minimal Anticipated Biological Effect Level (MABEL) derived from non-clinical studies.

A starting dose of 0.05 μg/kg was proposed for this study; following dose strength for escalation are: 0.5 μg/kg, 3.0 μg/kg, 15 μg/kg, 30 μg/kg, 45 μg/kg.

dose level #5

dose escalation, 30.0 ug/kg

Group Type EXPERIMENTAL

MTS105

Intervention Type BIOLOGICAL

MTS105 is a combination of mRNA, which encodes a therapeutic protein, and its delivery vehicle, a lipid nanoparticle (LNP). The starting dose is estimated based on the Minimal Anticipated Biological Effect Level (MABEL) derived from non-clinical studies.

A starting dose of 0.05 μg/kg was proposed for this study; following dose strength for escalation are: 0.5 μg/kg, 3.0 μg/kg, 15 μg/kg, 30 μg/kg, 45 μg/kg.

dose level #6

dose escalation, 45.0 ug/kg

Group Type EXPERIMENTAL

MTS105

Intervention Type BIOLOGICAL

MTS105 is a combination of mRNA, which encodes a therapeutic protein, and its delivery vehicle, a lipid nanoparticle (LNP). The starting dose is estimated based on the Minimal Anticipated Biological Effect Level (MABEL) derived from non-clinical studies.

A starting dose of 0.05 μg/kg was proposed for this study; following dose strength for escalation are: 0.5 μg/kg, 3.0 μg/kg, 15 μg/kg, 30 μg/kg, 45 μg/kg.

Interventions

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MTS105

MTS105 is a combination of mRNA, which encodes a therapeutic protein, and its delivery vehicle, a lipid nanoparticle (LNP). The starting dose is estimated based on the Minimal Anticipated Biological Effect Level (MABEL) derived from non-clinical studies.

A starting dose of 0.05 μg/kg was proposed for this study; following dose strength for escalation are: 0.5 μg/kg, 3.0 μg/kg, 15 μg/kg, 30 μg/kg, 45 μg/kg.

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

1. Histologically or cytologically confirmed diagnosis of hepatocellular carcinoma (HCC), excluding fibrolamellar or sarcomatoid subtypes, as well as mixed hepato-cholangiocellular carcinoma;
2. Positive for GPC3 expression per immunohistochemical (IHC) staining.
3. Failure of standard systemic therapies, including at least one immune checkpoint inhibitor and one targeted therapy (Tyrosine Kinase Inhibitors, and/or anti vascular endothelial growth factor agent).
4. Presence of a measurable tumor lesion (per RECIST/ mRECIST criteria).
5. Barcelona Clinical Liver Cancer Stage B or C (BCLC B/C)
6. Child-Pugh Score ≤ 6
7. ECOG score ≤ 1
8. Adequate organ and bone marrow function as defined by the following laboratory criteria:

1. Hematology: No blood transfusion or colony-stimulating factor therapy within 7 days prior to the first dose. The following hematological parameters should be met:Absolute neutrophil count ≥ 1.5 × 10\^9/L;Lymphocyte count ≥ 0.5 × 10\^9/L;Hemoglobin ≥ 90 g/L;Platelet count ≥ 75 × 10\^9/L;
2. Liver function:Total bilirubin ≤ 2.5 mg/dL;Albumin ≥ 28 g/L;Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 × ULN;
3. International Normalized Ratio (INR) ≤ 2.3;Oral anticoagulant therapy at a stable dose for at least 2 weeks. If oral warfarin is used, the patient must have an INR ≤ 3.0 and no bleeding events within 28 days prior to administration;
4. Renal function:Serum creatinine ≤ 1.5 × ULN, or endogenous creatinine clearance ≥ 45 mL/min (as determined by the CKD-EPI formula);Urinary protein \< 2+, or urinary protein ≥ 2+ but with 24-hour protein quantification ≤ 1.0 g
5. Cardiac function:Left ventricular ejection fraction (LVEF) ≥ 50%; No clinically significant abnormal ECG findings (chronic atrial fibrillation is allowed, provided it does not require medication);
9. Capable of full communication with the investigator, with the ability to understand and comply with study requirements, and able to understand and sign the informed consent form (ICF).
10. ≥18 years

Exclusion Criteria

1. Any known active intracranial metastases, or brain metastases that have been treated for less than 4 weeks.
2. Recent Antitumor Therapy:

1. Treatment with any immune checkpoint inhibitor within 4 weeks (28 days) prior to the first dose.
2. Received any investigational drug within 4 weeks prior to the first dose.
3. Received localized therapy for hepatocellular carcinoma (HCC), including but not limited to arterial chemoembolization (TACE), arterial infusion chemotherapy (HAIC), Y-90 radioembolization, ablative therapy, or stereotactic radiation therapy (SBRT), within 4 weeks prior to the first dose.
4. Received other anticancer therapies, such as multi-targeted tyrosine kinase inhibitors (mTKIs) and/or anti-VEGF therapies, within 3 weeks.
5. Received non-specific immunomodulatory therapy, including but not limited to interleukin, interferon, thymidine, etc., within 2 weeks prior to the first dose.
6. Received herbal or proprietary Chinese medicine for antitumor indications within 1 week prior to the first dose.
7. Previously received experimental treatment targeting GPC3 (patients may be enrolled if they remain positive for GPC3 upon testing).
3. History of liver transplantation or hematopoietic stem cell transplantation.
4. Unresolved toxicity from prior anticancer therapy (\> grade 1, according to CTCAE v5.0).
5. Major surgery (other than biopsy) within 28 days prior to the first dose.
6. Uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 90 mmHg).
7. Class III-IV heart failure by New York Heart Association (NYHA) criteria within 6 months prior to the first dose, unstable angina, myocardial infarction, bypass surgery, stent placement, cerebral infarction, or clinically significant valvular heart disease.
8. QTcF ≥ 450 ms in men and ≥ 470 ms in women (by Fridericia formula).
9. Severe infection within 4 weeks before the first dose (excluding viral hepatitis), or any signs or symptoms of active infection within 2 weeks before the first dose, or patients requiring antibiotic treatment within 2 weeks (excluding local medications and prophylactic antibiotics); unexplained fever \> 38.5°C before the first dose.
10. For HBV-associated HCC:

1. HBsAg (+) : less than 2 weeks of HBV antiviral standard treatment before the first administration of study drug, with an HBV DNA viral load ≥ 1000 IU/mL.
2. HBcAb (+) , HBsAg (-): HBV DNA viral load ≥ 1000 IU/mL.
11. Hepatitis C virus-infected subjects who have not completed 4 weeks of antiviral treatment.
12. Positive for human immunodeficiency virus (HIV+).
13. Subjects requiring systemic corticosteroids (equivalent dose of prednisone \> 10 mg/day) or other immunosuppressive drugs within 14 days prior to the first dose or during the study.
14. History of autoimmune disease requiring systemic treatment within 2 years prior to the first dose.
15. History of other malignancies within 2 years prior to the first dose (excluding cured skin basal cell carcinoma or squamous cell carcinoma, cervical carcinoma in situ, breast ductal carcinoma in situ, or other cancers that the investigator believes are cured and have an extremely low risk of recurrence).
16. Women who are pregnant or breastfeeding.
17. Any other condition that, in the opinion of the investigator, makes participation in the study inappropriate.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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METiS Pharmaceuticals

INDUSTRY

Sponsor Role collaborator

Shen Lin

OTHER

Sponsor Role lead

Responsible Party

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Shen Lin

Professor

Responsibility Role SPONSOR_INVESTIGATOR

Locations

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Peking University Cancer Hospital

Beijing, , China

Site Status RECRUITING

Countries

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China

Central Contacts

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Lin Professor, M.D

Role: CONTACT

Phone: 010 88196561

Email: [email protected]

Facility Contacts

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Lin Shen, Ph.D

Role: primary

Changsong Qi, M.D.

Role: backup

Lin Shen, Ph.D

Role: backup

Other Identifiers

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MTS105-01

Identifier Type: -

Identifier Source: org_study_id