Phase 1 Study of UCMYM802 Injection in Mesothelin-positive Advanced Malignant Solid Tumors

NCT06256055 | Recruiting Phase 1

• 1 other identifier: UCMYM802-Ⅰ
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Malignant Mesothelioma; Colorectal Cancer; Bile Duct Cancer; Rectal Cancer; Ovary Cancer; Pancreatic Cancer; Breast Cancer Female

Keywords

mRNA CAR-T; Solid tumor; mesothelin

Outcome Measures

Primary Outcomes (4)

• Treatment Emergent Adverse Event (TEAE)

  Incidence and severity of treatment emergent adverse events.

  2 years

• Treatment Related Adverse Event (TRAE)

  Incidence and severity of treatment related adverse events

  2 years

• Adverse Events of Special Interest (AESI)

  Incidence and severity of adverse event of special interest

  2 years

• Incidence of Dose-limiting Toxicities (DLTs)

  Incidence and severity of dose-limiting toxicities (DLTs) following infusion of UCMYM802 injection at each dose level.

  4 weeks

Secondary Outcomes (11)

• Bio-distribution of UCMYM802

  3 months

• Peak Plasma Concentration (Cmax)

  3 months

• Time to Maximum Plasma Concentration (Tmax)

  3 months

• Area Under Curve (AUC)

  3 months

• Cytokine Level in Peripheral Blood

  2 years

Study Arms (1)

UCMYM802 Injection

EXPERIMENTAL

Active ingredient：Anti-MSLN CAR+ T cell

Biological: UCMYM802 Injection

Interventions

UCMYM802 Injection BIOLOGICAL

1×10\^8\~2×10\^9 cells will be infused intravenously for 4 times.

UCMYM802 Injection

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• Coagulation functions: Activated partial thromboplastin time (APTT) ≤ 1.5×ULN.
• Renal functions: Serum creatinine (Cr)≤1.5 × ULN; or Creatinine clearance rate (Ccr) ≥ 60 mL/min（Cockcroft-Gault）.
• Cardiac functions: Left ventricular ejection fraction (LVEF) \> 50% (confirmed by ECHO).
• Lung fuction:Pulse oxygen saturation (SpO2) \> 95% at rest without oxygenation
• Women of childbearing potential (WCBP) must have negative results on a serum pregnancy test, and WCBP or Male who have partners of reproductive potential must agree to use effective contraceptive methods to avoid pregnancy throughout the screening and study period until 1 year after the last cell infusion;

You may not qualify if:

• 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:
• Presence of uncontrolled severe active infection (e.g., sepsis, bacteremia, and viremia, etc.);
• Congestive heart failure classified as \> class I based on New York Heart Association (NYHA);
• Clinically significant severe aortic stenosis and symptomatic mitral valve stenosis;
• QTc \> 450 msec or QTc \> 480 msec as shown by ECG in patients with bundle branch block;
• Presence of uncontrolled clinically significant arrhythmias within 6 months prior to signing the ICF;

Sponsors & Collaborators

• UTC Therapeutics Inc.: lead
• Peking University Cancer Hospital & Institute: collaborator

Study Sites (1)

Peking University Cancer Hospital & Institute

Beijing, China

RECRUITING

MeSH Terms

Conditions

Mesothelioma, Malignant; Colorectal Neoplasms; Bile Duct Neoplasms; Rectal Neoplasms; Ovarian Neoplasms; Pancreatic Neoplasms

Condition Hierarchy (Ancestors)

Mesothelioma; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Biliary Tract Neoplasms; Bile Duct Diseases; Biliary Tract Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Pancreatic Diseases

Study Officials

• Lin Shen, Doctor

  Peking University Cancer Hospital & Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Changsong Qi, Doctor

CONTACT

0086-10-88196813; xiwangpku@126.com

Chang Liu

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Accelerated titration design and 3+3 design

Study Record Dates

• First Submitted: January 22, 2024
• First Posted: February 13, 2024
• Study Start: March 5, 2024
• Primary Completion: March 1, 2025
• Study Completion: April 1, 2025
• Last Updated: July 24, 2024

Record last verified: 2024-03

Locations

CN (1)