Mts105 for Advanced Hepatocellular Carcinoma

NCT06689540 | Recruiting Phase 1

• 1 other identifier: MTS105-01
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

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

Keywords

hcc; mts105; metis; mRNA; LNP

Outcome Measures

Primary Outcomes (2)

• Incidence of treatment-emergent adverse events (TEAEs), and serious adverse events (SAEs).

  Incidence of TEAEs,and SAEs.

  From enrollment to the end of treatment at 4 weeks

• Maximal Tolerance Dose (MTD)

  Determined based on the occurrence of dose-limiting toxicity (DLT).

  Within the first 28-days following first dose

Secondary Outcomes (9)

• Peak Plasma Concentration (Cmax)

  Within the first 28-days following first dose

• Area under the plasma concentration versus time curve (AUC)

  Within the first 28-days following first dose

• Time for peak concentration (Tmax)

  Within the first 28-days following first dose

• Elimination half-life

  Within the first 28-days following first dose

• Steady-state concentration

  Within the first 28-days following first dose

Other Outcomes (1)

• Concentration of anti-drug antibodies

  through study completion, an average of 1 year

Study Arms (6)

dose level #1

EXPERIMENTAL

Starting dose, 0.05 ug/kg

Biological: MTS105

dose level #2

EXPERIMENTAL

dose escalation, 0.5 ug/kg

Biological: MTS105

dose level #3

EXPERIMENTAL

dose escalation, 3.0 ug/kg

Biological: MTS105

dose level #4

EXPERIMENTAL

dose escalation, 15.0 ug/kg

Biological: MTS105

dose level #5

EXPERIMENTAL

dose escalation, 30.0 ug/kg

Biological: MTS105

dose level #6

EXPERIMENTAL

dose escalation, 45.0 ug/kg

Biological: MTS105

Interventions

MTS105 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 #1; dose level #2; dose level #3; dose level #4; dose level #5; dose level #6

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed diagnosis of hepatocellular carcinoma (HCC), excluding fibrolamellar or sarcomatoid subtypes, as well as mixed hepato-cholangiocellular carcinoma;
• Positive for GPC3 expression per immunohistochemical (IHC) staining.
• 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).
• Presence of a measurable tumor lesion (per RECIST/ mRECIST criteria).
• Barcelona Clinical Liver Cancer Stage B or C (BCLC B/C)
• Child-Pugh Score ≤ 6
• ECOG score ≤ 1
• Adequate organ and bone marrow function as defined by the following laboratory criteria:
• 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;
• Liver function:Total bilirubin ≤ 2.5 mg/dL;Albumin ≥ 28 g/L;Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 × ULN;
• 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;
• 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
• 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);
• 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).
• ≥18 years

You may not qualify if:

• Any known active intracranial metastases, or brain metastases that have been treated for less than 4 weeks.
• Recent Antitumor Therapy:
• Treatment with any immune checkpoint inhibitor within 4 weeks (28 days) prior to the first dose.
• Received any investigational drug within 4 weeks prior to the first dose.
• 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.
• Received other anticancer therapies, such as multi-targeted tyrosine kinase inhibitors (mTKIs) and/or anti-VEGF therapies, within 3 weeks.
• Received non-specific immunomodulatory therapy, including but not limited to interleukin, interferon, thymidine, etc., within 2 weeks prior to the first dose.
• Received herbal or proprietary Chinese medicine for antitumor indications within 1 week prior to the first dose.
• Previously received experimental treatment targeting GPC3 (patients may be enrolled if they remain positive for GPC3 upon testing).
• History of liver transplantation or hematopoietic stem cell transplantation.
• Unresolved toxicity from prior anticancer therapy (\> grade 1, according to CTCAE v5.0).
• Major surgery (other than biopsy) within 28 days prior to the first dose.
• Uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 90 mmHg).
• 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.
• QTcF ≥ 450 ms in men and ≥ 470 ms in women (by Fridericia formula).

Sponsors & Collaborators

• Shen Lin: lead
• METiS Pharmaceuticals: collaborator

Study Sites (1)

Peking University Cancer Hospital

Beijing, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Liver Neoplasms

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Central Study Contacts

Lin Professor, M.D

CONTACT

010 88196561; Linshenpku@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Model Details: Bayesian Optimal Interval (BOIN) Design

Study Record Dates

• First Submitted: November 8, 2024
• First Posted: November 14, 2024
• Study Start: November 18, 2024
• Primary Completion: December 31, 2025
• Study Completion (Estimated): December 31, 2026
• Last Updated: December 24, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)