A Phase I Clinical Study to Evaluate the Safety and Efficacy of IM96 CAR-T Cell Injection in Advanced Colorectal Cancer
Overview
- Phase
- Phase 1
- Status
- Recruiting
- Sponsor
- Beijing Immunochina Medical Science & Technology Co., Ltd.
- Enrollment
- 9
- Locations
- 1
- Primary Endpoint
- Incidence of Treatment Related adverse events (AEs)
Overview
Brief Summary
This study, a single-center, open, single-dose clinical study, was designed to evaluate the safety and efficacy of IM96 CAR-T cells in treating patients with advanced colorectal cancer
Detailed Description
This study is planned to enroll 6-12 patients with advanced colorectal cancer, using a modified "3+3" design for dose escalation, with two dose groups of 12×10^8 CAR-T cells and 20×10^8 CAR-T cells. 3-6 subjects are planned to be enrolled in each dose group to assess their safety, and if the incidence of horizontal dose-limiting toxicity (DLT) is ≤1/6 within 28 days after transfusion in one dose group, the next dose group can be started. If the incidence of horizontal dose-limiting toxicity (DLT) in a dose group is ≤1/6 within 28 days after transfusion, transfusion of cells from the next dose group can be initiated.
This study will be divided into a screening period, a cell collection period, a chemotherapy pretreatment period, a return infusion and a follow-up period, and within 28 days of return infusion the investigator will assess whether a DLT (Dose limited toxicity) event has occurred to confirm the safety of this dose group.
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
- •The age is 18 to 75 years (including boundary values) and the gender is not limited;
- •Patients with advanced GI tumors diagnosed by pathohistology, mainly:
- •(1)Patients with metastatic colorectal cancer who have failed or are intolerant to second-line and above standard therapy;
- •The standardized systemic treatment received by the patient must be in accordance with the Chinese Society of Clinical Oncology (CSCO) Guidelines for the Treatment of Colorectal and Gastric Cancer, 2024 Edition;
- •Claims of treatment intolerance: Patients who are unable to continue current effective systemic standardized treatment due to toxic side effects such as grade ≥3 vomiting, diarrhea, abdominal pain, bone marrow suppression, etc., and who do not accept refusal for financial and personal reasons; 3.Presence of at least one measurable lesion that meets RECIST 1.1 criteria; 4.Patients must provide a tumor sample within 2 years that meets the requirements (paraffin block or number of unstained sections that meet the testing requirements set by the Institute) that is positive for GUCY2C expression by immunohistochemistry; 5.Survival is expected to be more than 3 months; 6.Eastern cooperative oncology group (ECOG) score of 0-1 (refer to Attachment 2); 7.Women of childbearing potential who have a negative blood pregnancy test prior to the start of the trial and who agree to use effective contraception during the trial and up to the last follow-up visit; male patients whose partners are of childbearing potential agree to use effective contraception during the trial and up to the last follow-up visit 8.Laboratory tests should meet at least the indicators specified below:
- •Hemoglobin (Hb) ≥ 90 g/L;
- •Neutrophil count (Absolute neutrophil count, ANC) ≥ 1.5 x 10\^9/L;
- •Platelet count (PLT) ≥ 75 x 10\^9/L;
- •Absolute lymphocyte value ≥ 0.6 x 10\^9/L;
- •Lymphocytes make up ≥10% of white blood cells;
Exclusion Criteria
- •Presence of brain metastases;
- •Patients who have previously received or are awaiting an organ transplant;
- •Toxicity due to prior therapy not stabilized or recovered to ≤ grade 1 (except in cases judged by the investigator to be not clinically significant);
- •Plasmapheresis (e.g., pleural effusion, abdominal effusion, pericardial effusion) with symptoms of compression that cannot be controlled with treatment;
- •Autoimmune disease requiring systemic immunosuppressive therapy (e.g., Crohn's disease, rheumatoid arthritis, systemic lupus) within 2 years prior to the start of screening;
- •Presence of chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD), and clinically significant pulmonary function test abnormalities;
- •Use of any of the following medications or treatments during the designated time period prior to cell collection:
- •Therapeutic doses of corticosteroids have been used within 7 days prior to cell collection. However, topical and inhaled steroids are permitted;
- •Received chemotherapeutic agents within 1 week prior to cell collection. Enrollment was allowed if the oral chemotherapeutic drug had passed at least 3 half-lives prior to cell collection;
- •Those who used drugs to stimulate bone marrow hematopoietic cell production within 5 days prior to cell collection;
Arms & Interventions
IM96 CAR-T Cells
After preconditioning with chemotherapy, IM96 CAR-T Cells will be evaluated
Intervention: IM96 CAR-T Cells (Biological)
Outcomes
Primary Outcomes
Incidence of Treatment Related adverse events (AEs)
Time Frame: Up to 28 days after CAR-T cell infusion
Incidence of adverse events associated with IM96 CAR-T cell infusion within 28 days of IM96 CAR-T cell infusion, type, frequency, and severity of abnormal clinically significant vital signs, electrocardiograms, and laboratory tests examined, including dose-limiting toxicity
Secondary Outcomes
- Objective remission rate (ORR)(At 28 days, 3 months, 6 months and 12 months after CAR-T cell infusion)
- Progression-free survival (PFS)(At 28 days, 3 months, 6 months and 12 months after CAR-T cell infusion)
- Disease control rate (DCR)(At 28 days, 3 months, 6 months and 12 months after CAR-T cell infusion)
- Duration of response (DOR)(At 28 days, 3 months, 6 months and 12 months after CAR-T cell infusion)
- Overall survival (OS)(At 28 days, 3 months, 6 months and 12 months after CAR-T cell infusion)
- AUC (Area Under Curve) 0-D90(Up to 90 days after CAR-T cell infusion)
- Cmax (Peak Concentration)(Up to 28 days after CAR-T cell infusion)
- Tmax (Peak Time)(Up to 28 days after CAR-T cell infusion)
- Tumor markers CA19-9(At 28 days, 3 months, 6 months and 12 months after CAR-T cell infusion)
- Tumor markers CEA(At 28 days, 3 months, 6 months and 12 months after CAR-T cell infusion)