A First-In-Human, Single Arm, Open-label, Phase 1 Dose-Escalation Study of UCMYM802 Injection in Mesothelin-positive Advanced Malignant Solid Tumors

UTC Therapeutics Inc.1 site in 1 country24 target enrollmentMarch 5, 2024

ConditionsMalignant Mesothelioma Colorectal Cancer Bile Duct Cancer Rectal Cancer Ovary Cancer Pancreatic Cancer Breast Cancer Female

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: Malignant Mesothelioma
Sponsor: UTC Therapeutics Inc.
Enrollment: 24
Locations: 1
Primary Endpoint: Adverse Events of Special Interest (AESI)
Status: Recruiting
Last Updated: last year

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

This is a first-in-human, single-arm, open-label, dose escalation clinical study to evaluate the safety, tolerability, pharmacokinetic and pharmacodynamic characteristics, immunogenicity and preliminary efficacy of UCMYM802 (Circular mRNA encoding Anti-Mesothelin CAR-T) injection in patients with Mesothelin-positive advanced malignant solid tumors.

Detailed Description

All subjects who qualified after screening will receive the proposed dose of UCMYM802 injection once a week, 4 times in total. The Starting Dose of cell injection was set at 1×10\^8, and the maximum dose was set at 2.0×10\^9.

Registry

clinicaltrials.gov

Start Date

March 5, 2024

End Date

April 2025

Last Updated

last year

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

UTC Therapeutics Inc.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•18 to 70 years old,regardless of gender
•Diagnosed Patients with malignant solid tumors confirmed histopathologically (including but not limited to mesothelioma, pancreatic cancer, biliary tract cancer, lung cancer, ovarian cancer, gastric cancer, colorectal cancer, thymus cancer, esophageal cancer, breast cancer, and endometrial cancer, etc.) who fail or cannot tolerate standard treatment or lack effective treatment methods as defined by CSCO and NCCN guidelines
•At least have one evaluable lesion;
•Patients who Can provide tumor tissue samples or tumor samples can be obtained through methods such as tumor biopsy;
•Positive expression of MSLN in tumor cells confirmed by Immunohistochemistry (IHC) or immunocytochemistry (ICC) staining
•Eastern Cooperative Oncology Group (ECOG) performance score at 0 or 1;
•Life expectancy ≥ 3 months.
•The organ function must meet the following requirements:
•Hematological functions: Absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L (Without receiving G-CSF support within 7 days prior to laboratory examination); Absolute Lymphocyte Count (ALC) ≥ 0.5 × 10\^9/L; Hemoglobin (HGB) ≥ 80 g/L (without receiving any blood transfusion or erythropoietin stimulating agent therapy within 7 days before the laboratory examination);Platelet count (PLT) ≥ 75 × 10\^9/L (Without receiving platelet transfusion and TPO within 7 days before the laboratory examination)；
•Hepatic functions: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 × upper limit of normal (ULN)(for patients with primary liver tumors or liver metastases ，AST and ALT≤ 5.0× ULN)；Total bilirubin (TBIL) ≤ 1.5 × ULN(for patients with primary liver tumors or liver metastases，TBIL≤ 3.0× ULN；patients with Gilbert's Syndrome，TBIL≤3×ULN and Direct bilirubin≤ 1.5 × ULN).

Exclusion Criteria

•Have received systemic antitumor therapy involving cytotoxic chemical agents, monoclonal antibodies or immunotherapy within 4 weeks or 5 half-lives (whichever is shorter) prior to signing the informed consent form（ICF）; Have received systemic glucocorticoids (prednisone or other equivalent hormone at a dose ≥ 10 mg/day) or other treatments to suppress the immune system within 2 weeks prior to signing the ICF; Have received systemic antitumor therapy involving biologics or other approved small molecule targeted inhibitors within 1 week or 5 half-lives (whichever is shorter) prior to signing the ICF; Have received treatments with Chinese herbal medicines (CHM) and Chinese proprietary medicines (CPM) that has an antitumor indication within 1 week prior to signing the ICF;
•Pregnant or lactating women;
•The finding of Positive hepatitis B surface antigen (HBsAg) or positive hepatitis B core antibody (HBcAb) and the result of quantitative HBV DNA test in peripheral blood is above the lower limit of detection (LLOD); positive Hepatitis C virus (HCV) antibody, and the result of quantitative HCV RNA test in peripheral blood is above the LLOD; The presence of positive Human immunodeficiency virus (HIV) antibody; positive Syphilis antibody test;
•Patients with Epstein-Barr Virus (EBV) DNA positive.
•Non-hematologic toxicity due to prior therapy (surgery, chemotherapy, radiation, targeted therapy, and immunotherapy, etc.) have not resolved to ≤ CTCAE grade 1 (except alopecia, peripheral sensory nerve disorders);
•Have received any prior xenotransplantation of tissues /organs (including bone marrow transplantation, stem cell transplantation, liver transplantation, and kidney transplantation, etc.), except for transplants that do not require immunosuppression (e.g., corneal graft and hair transplantation, etc.);
•Previoulsly received any anti mesothelin (MSLN) treatment and any genetically modified cell therapy within 6 months prior to signing the informed consent form;
•Have undergone major surgery and not fully recovered within 4 weeks prior to signing informed consent or have a history of severe trauma that have not recovered, or planned to receive major surgery within 12 weeks after cell infusion;
•Presence of known CNS metastases
•Presence of clinically significant systemic disease (e.g., severe active infection or significant dysfunctions of the heart, lungs, liver, nervous system, or other organs) that, at the discretion of the investigator, impairs the patient's ability to tolerate the treatment specified in this trial protocol or significantly increases the risk of complications. Including but not limited to: