NCT05775666
Not yet recruiting
Phase 1
Exploratory Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of UCLM802 (Anti-Mesothelin CAR-T) Cell Injection in Patients With Mesothelin-positive Advanced Malignant Solid Tumors
Peking University0 sites87 target enrollmentStarted: March 2023Last updated:
ConditionsSolid Tumor
Overview
- Phase
- Phase 1
- Status
- Not yet recruiting
- Sponsor
- Peking University
- Enrollment
- 87
- Primary Endpoint
- Adverse Events (AEs)
Overview
Brief Summary
This is a single-arm, open-label, exploratory clinical study to evaluate the safety, tolerability and preliminary efficacy of UCLM802 (Anti-Mesothelin CAR-T) cell injection in patients with Mesothelin-positive advanced malignant solid tumors.
Detailed Description
This study will include two parts, dose escalation phase (accelerated titration and 3+3 design) followed by a dose expansion phase (Cohort 1: Malignant mesothelioma; Cohort 2: Advanced malignant tumors of the digestive system; Cohort 3: Other advanced malignant solid tumors.).
All eligible participants will receive a conditioning chemotherapy regimen of fludarabine and cyclophosphamide followed by UCLM802 cell injection.
The dose escalation phase will determine the maximum tolerated dose (MTD) of UCLM802 cell injection. Additional patients will be enrolled in the dose expansion phase to further characterize the safety profile and evaluate the efficacy of UCLM802 cell injection, and establish recommended phase 2 dose (RP2D).
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •18 to 75 years old (including cut-off value), gender is not limited
- •Solid tumors that histological diagnosis of malignancy refractory to, or relapsing after standard therapy, including but not limited to mesothelioma, pancreatic cancer, biliary tract cancer, lung cancer, ovarian cancer, gastric cancer, bowel cancer, thymic carcinoma, esophageal cancer, breast cancer, endometrial cancer.
- •At least one measurable lesion according to RECIST v1.
- •Mesothelin should be positive confirmed by Immunohistochemistry/Immunocytochemistry (IHC/ICC) in tumor tissue samples.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Life expectancy ≥ 3 months.
- •Adequate function defined as:
- •Hematological functions: Absolute neutrophil count (ANC) ≥ 1.5 × 109/L (Patients should not receive G-CSF support within 7 days before laboratory examination); Absolute Lymphocyte Count (ALC) ≥ 0.5 × 109/L; Hemoglobin (HGB) ≥ 80 g/L (Patients should not be transfused red cells within 7 days before the laboratory examination); Platelet count (PLT) ≥ 75 × 109/L (Patients should not receive transfusion support within 7 days before the laboratory examination).
- •Hepatic functions: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 × upper limit of normal (ULN); AST and ALT of patients with liver metastasis ≤ 5 × ULN; Total bilirubin (TBIL) ≤ 1.5 × ULN; TBIL of patients with liver metastasis must ≤ 3.0 × ULN; TBIL of patients with Gilbert's Syndrome ≤ 3.0 × ULN and Direct bilirubin (DBIL) ≤ 1.5 × ULN.
- •Coagulation functions: International normalized ratio (INR) ≤ 1.5 × ULN; Activated partial thromboplastin time (APTT) ≤ 1.5 × ULN (Except for patients who are receiving therapeutic anticoagulants.).
Exclusion Criteria
- •Patients have received systemic therapy with cytotoxic chemicals, monoclonal antibodies, or immunotherapy within 4 weeks or 5 half-lives (which is shorter) prior to signing informed consent; Patients have received systemic glucocorticoids (prednisone at a dose of ≥10 mg per day or equivalent) or other immune-suppressive therapy within 2 weeks prior to signing informed consent; Patients have received systemic antitumor therapy with a biologic agent or other approved targeted small-molecule inhibitor within 1 week or five half-lives (which is shorter) prior to signing informed consent; Patients have received Chinese herbal medicine or Chinese patent medicine with anti-tumor indication within 1 week prior to signing informed consent.
- •Pregnant or lactating women.
- •Patients with hepatitis B surface antigen (HBsAg) positive. Patients who is hepatitis B core antibody (HBcAb) positive and the quantification of HBV DNA in peripheral blood is higher than the lower limit of detection. Patients who is hepatitis C virus (HCV) antibody positive and quantification of HCV DNA in peripheral blood is higher than the lower limit of detection. Patients with human immunodeficiency virus (HIV) antibody positive, or syphilis antibody positive.
- •The toxicities caused by the prior therapy (surgery, chemotherapy, radiotherapy, targeted therapy, immunotherapy, etc.) have not recovered to grade 1 according to CTCAE, except for hair loss and peripheral sensory nerve disorders.
- •Have received any allogeneic tissue/organ transplantation (including bone marrow transplantation, stem cell transplantation, liver transplantation, kidney transplantation), except for the transplantation that does not require immunosuppressive therapy (such as: corneal transplantation, hair transplantation.)
- •Patients have received anti-mesothelin CAR-T cell therapy.
- •Patients who have history of major surgery and unrecovered severe trauma within 4 weeks prior to signing informed consent; or plan to have major surgery within 12 weeks of cell therapy.
- •Presence of known central nervous system metastases, but the following patients will be allowed: a) Asymptomatic brain metastases; b) Clinically stable (no radiographic progression within 4 weeks before apheresis and return of any neurologic symptoms to baseline), and with no need for corticosteroids or other treatment for brain metastases for ≥ 4 weeks.
- •Patients with clinically significant systemic disease (such as: severe active infection or significant cardiac, pulmonary, hepatic, nervous system, or other organ dysfunction) that evaluated by the investigator would impair the patients' ability to tolerate the treatments used in this study or significantly increase the risk of complications.
- •Uncontrolled severe active infection (sepsis, bacteremia, viremia, etc.);
Outcomes
Primary Outcomes
Adverse Events (AEs)
Time Frame: 2 years
Incidence and severity of adverse events.
Serious Adverse Events (SAEs)
Time Frame: 2 years
Incidence and severity of serious adverse events.
Identification of Maximum Tolerated Dose (MTD) & Incidence of Dose-limiting Toxicities (DLTs)
Time Frame: 4 weeks after the CAR-T cells infusion
Incidence and severity of dose-limiting toxicities (DLTs) following infusion of UCLM802 cell injection, at each dose level tested in dose escalation phase.
Adverse Events of Special Interest (AESI)
Time Frame: 2 years
Incidence and severity of adverse event of special interest.
Secondary Outcomes
- Tmax of CAR copies(2 years)
- Objective Response Rate (ORR)(2 years)
- Disease Control Rate (DCR)(2 years)
- Progression-Free Survival (PFS)(2 years)
- Duration of Overall Response (DOR)(2 years)
- Overall Survival (OS)(2 years)
- Cytokine Level in Peripheral Blood(2 years)
- Anti-drug Antibodies(2 years)
- Cmax of CAR copies(2 years)
- AUC of CAR copies(2 years)
Investigators
Shen Lin
Professor
Peking University
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