Malignant MesotheliomaPhase 1NCT06256055
Phase 1 Study of UCMYM802 Injection in Mesothelin-positive Advanced Malignant Solid Tumors
A Phase 1 study testing UCMYM802 Injection in people with Malignant Mesothelioma and Colorectal Cancer, run by UTC Therapeutics Inc. at 1 site in China.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Malignant Mesothelioma, Colorectal Cancer, Bile Duct Cancer
- What is being tested?
- UCMYM802 Injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteChina
- Study dates
- 5 Mar 2024to Apr 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
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- 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;
- Voluntary signing informed consent form(s) indicating that they are willing to participate in the study and are able to comply with the protocol.
Who cannot join
- 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.);
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- 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;
- Presence of acute coronary syndrome within 6 months prior to signing the ICF (e.g., unstable angina and myocardial infarction);
- Hypertension (systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 100 mmHg) or pulmonary hypertension that has not been controlled by medication;
- Cerebrovascular accident within 6 months prior to signing informed consent, including: Transient ischemic attack (TIA), brain infarction, cerebral hemorrhage and subarachnoid hemorrhage;
- Presence of active, chronic or relapsing (within 1 year prior to signing the ICF) severe autoimmune disorder or history of immune-mediated disease requiring steroid or other immunosuppressive therapy, including but not limited to systemic lupus erythematosus, psoriasis, rheumatoid arthritis, inflammatory bowel disease, Hashimoto's thyroiditis, autoimmune thyroid disorder, and multiple sclerosis, etc. Except: Hypothyroidism that can be controlled by thyroid hormone replacement therapy alone, skin diseases that do not require systemic treatment (e.g. vitiligo and psoriasis), celiac disease that is already under control;
- Presence of any form of primary or secondary immunodeficiency, such as: Severe combined immunodeficiency (SCID);
- Possibility of bleeding due to esophageal or gastric varices as judged by the investigator.
- History of severe systemic hypersensitivity reactions to the drugs/components used in this trial [such as: fludarabine, cyclophosphamide, dimethyl sulfoxide (DMSO), low molecular dextran, and human serum albumin (HSA), etc.];
- Have received a live attenuated vaccine within 4 weeks prior to signing the ICF;
- Participation in another clinical trial within 4 weeks prior to signing the ICF(Enrolled and given of investigational drugs/treatments);
- History of another malignancy within the previous 5 years (except adequately treated non-melanoma skin cancer and in situ cancer in the following sites: breast, stomach, colon, and cervical, etc.);
- Prior neuropsychiatric disorders diagnosed by International Classification of Diseases 11th Revision (ICD-11) criteria for mental and behavioral disorders or neuropsychiatric disorders to be excluded as assessed by the investigator, including but not limited to epilepsy, schizophrenia, dementia, addictive behaviors due to drugs and alcohol, etc.;
- Presence of other conditions that, in the judgment of the investigator, would preclude the patient from participating in this trial.
Trial locations and contacts
1 site in 1 country.
Chang Liu contact
China1 site, 1 recruiting
- Recruiting
Peking University Cancer Hospital & Institute
Beijing
Changsong Qi, 0086-10-88196813
About this study
Official title: A First-In-Human, Single Arm, Open-label, Phase 1 Dose-Escalation Study of UCMYM802 Injection in Mesothelin-positive Advanced Malignant Solid Tumors
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.
Read the 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.
- Conditions
- Malignant Mesothelioma, Colorectal Cancer, Bile Duct Cancer, Rectal Cancer, Ovary Cancer, Pancreatic Cancer
- Being tested
- UCMYM802 Injection
- Keywords
- mRNA CAR-T, Solid tumor, mesothelin
- Medical subject headings
- Mesothelioma, Malignant, Colorectal Neoplasms, Bile Duct Neoplasms, Rectal Neoplasms, Ovarian Neoplasms, Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
UCMYM802 InjectionBiological
1×10^8~2×10^9 cells will be infused intravenously for 4 times.
| Study group | Role | What they receive |
|---|---|---|
| UCMYM802 Injection | Experimental | Active ingredient：Anti-MSLN CAR+ T cell Receives: Biological: UCMYM802 Injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Treatment Emergent Adverse Event (TEAE)
Incidence and severity of treatment emergent adverse events.
Measured: 2 years
Treatment Related Adverse Event (TRAE)
Incidence and severity of treatment related adverse events
Measured: 2 years
Adverse Events of Special Interest (AESI)
Incidence and severity of adverse event of special interest
Measured: 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.
Measured: 4 weeks
Secondary outcomes (11)
Bio-distribution of UCMYM802
CAR copies will be measured by qPCR to evaluate the expansion and persistence of CAR-T cells in vivo.
Measured: 3 months
Peak Plasma Concentration (Cmax)
The maximum (peak) of CART cells observed in peripheral blood
Measured: 3 months
Time to Maximum Plasma Concentration (Tmax)
The time for CART cells to reach maximum（peak）in peripheral blood
Measured: 3 months
Area Under Curve (AUC)
The area under curve (AUC) from time zero to 24, 48 ,72 hours and AUC0-tlast, AUC0-inf in peripheral blood
Measured: 3 months
Cytokine Level in Peripheral Blood
The concentration level of CAR-T cell related cytokines/chemokines in peripheral blood
Measured: 2 years
Anti-drug Antibodies
Positive rate of anti-drug antibody in the serum of subjects
Measured: 2 years
Objective Response Rate (ORR)
The proportion of subjects who achieved complete response (CR) or partial response (PR) according to the RECIST v1.1 criteria
Measured: 2 years
Disease Control Rate (DCR)
The proportion of subjects who achieved complete response (CR), partial response (PR), or disease stability (SD) according to the RECIST v1.1 criteria
Measured: 2 years
Duration of Response (DoR)
The time from the initial evaluation as complete remission (CR) or partial remission (PR) to the initial evaluation as disease progression (PD) or death from any cause
Measured: 2 years
Progression-Free Survival (PFS)
The time from initial CART cell infusion to first disease progression (PD) or death for any cause
Measured: 2 years
Overall Survival (OS)
The time from initial CART cell infusion to death due to any reasons.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Feb 2024
- Study start5 Mar 2024
- Primary completionMar 2025 (estimated)
- Study completionApr 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Malignant MesotheliomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Accelerated titration design and 3+3 design
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- UTC Therapeutics Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Peking University Cancer Hospital & Institute
- Responsible party
- Sponsor
- Investigators
- Lin Shen, Doctor, Principal investigator, Peking University Cancer Hospital & Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06256055
- Sponsor's protocol ID
- UCMYM802-Ⅰ
- Status last verified
- Mar 2024
- First submitted
- 22 Jan 2024
- Last updated
- 24 Jul 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A First-In-Human, Single Arm, Open-label, Phase 1 Dose-Escalation Study of UCMYM802 Injection in Mesothelin-positive Advanced Malignant Solid Tumors
- ClinicalTrials.gov ID
- NCT06256055
- Acronym / sponsor ID
- UCMYM802-Ⅰ
- Conditions
- Malignant Mesothelioma, Colorectal Cancer, Bile Duct Cancer, Rectal Cancer, Ovary Cancer, Pancreatic Cancer
- Keywords
- mRNA CAR-T, Solid tumor, mesothelin
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- UTC Therapeutics Inc.Industry (pharma, biotech, devices)
- Collaborators
- Peking University Cancer Hospital & Institute
- Study start
- 5 Mar 2024 (actual)
- Primary completion
- Mar 2025 (estimated)
- Study completion
- Apr 2025 (estimated)
- First posted
- 13 Feb 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Accelerated titration design and 3+3 design
| Arm | Type | Receives |
|---|---|---|
| UCMYM802 Injection | Experimental | Biological: UCMYM802 InjectionActive ingredient：Anti-MSLN CAR+ T cell |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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
Key exclusion criteria (27 listed)
- 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);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| UCMYM802 Injection1×10^8~2×10^9 cells will be infused intravenously for 4 times. | Biological | UCMYM802 Injection |
Primary outcome
Treatment Emergent Adverse Event (TEAE)
Time frame: 2 years
Incidence and severity of treatment emergent adverse events.
Treatment Related Adverse Event (TRAE)
Time frame: 2 years
Incidence and severity of treatment related adverse events
Adverse Events of Special Interest (AESI)
Time frame: 2 years
Incidence and severity of adverse event of special interest
Incidence of Dose-limiting Toxicities (DLTs)
Time frame: 4 weeks
Incidence and severity of dose-limiting toxicities (DLTs) following infusion of UCMYM802 injection at each dose level.
11 secondary outcomes
Bio-distribution of UCMYM802
Time frame: 3 months
Peak Plasma Concentration (Cmax)
Time frame: 3 months
Time to Maximum Plasma Concentration (Tmax)
Time frame: 3 months
Area Under Curve (AUC)
Time frame: 3 months
Cytokine Level in Peripheral Blood
Time frame: 2 years
Anti-drug Antibodies
Time frame: 2 years
Objective Response Rate (ORR)
Time frame: 2 years
Disease Control Rate (DCR)
Time frame: 2 years
Duration of Response (DoR)
Time frame: 2 years
Progression-Free Survival (PFS)
Time frame: 2 years
Overall Survival (OS)
Time frame: 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jul 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Chang Liu contact
Lin Shen, Doctor principal investigator
Peking University Cancer Hospital & Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing UCMYM802 Injection in people with Malignant Mesothelioma and Colorectal Cancer, run by UTC Therapeutics Inc. at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 24 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Changsong Qi, Doctor (0086-10-88196813, xiwangpku@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Treatment Emergent Adverse Event (TEAE) (time frame: 2 years). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jul 2024.