Tumor-Specific T-Cells (cCTL:GL01) for Advanced Gastrointestinal Cancer

Official title

A Single-Arm, Interventional, Exploratory Clinical Study of Tumor-Specific Cytotoxic T-Cell Injection (cCTL:GL01) for the Treatment of Advanced Gastrointestinal Tumors

Overview

This clinical trial is designed to study an investigational cell therapy called cCTL-GL01 in patients with advanced gastrointestinal cancers (including cancers of the stomach, esophagus, colon, or rectum) that have not responded well to standard treatments. The main goals of this study are to find out: If cCTL-GL01 is safe and what side effects it might cause; How well cCTL-GL01 works to control or shrink tumors.

Detailed description

cCTL-GL01 is a cellular immunotherapy utilizing specialized T-cells engineered to recognize, target, and eliminate cancer cells. For patients enrolled in this clinical study, the therapeutic process comprises the following phases:

Preconditioning (Pre-treatment): Patients undergo a short course of lymphodepleting conditioning to optimize the host immune environment and facilitate the engraftment and expansion of the infused T-cells.

cCTL-GL01 Infusion and Combination Therapy: cCTL-GL01 cells are administered via intravenous (IV) infusion, supplemented by a combination therapy designed to enhance the in vivo persistence and therapeutic efficacy of the infused T-cells.

Safety and Efficacy Monitoring: Subjects undergo rigorous monitoring to ensure clinical safety and evaluate therapeutic response. This includes active surveillance for immunotherapy-related adverse events (particularly Cytokine Release Syndrome, or CRS), routine laboratory examinations (blood panels), and regular radiographic assessments (e.g., CT or MRI scans) to evaluate tumor response.

Interventions

• Drug Biological/Vaccine
  Following lymphodepleting conditioning and a 2-3 day chemotherapy washout period, patients will begin receiving twice-weekly infusions of autologous cCTL cells. This study is designed such that the first three cCTL infusions for each patient will follow a stepwise dose escalation of the effective dose, specifically 1-2×107 cCTL/Kg、3-4×107 cCTL/Kg、4-5×107 cCTL/Kg; safety will be evaluated during this period to determine subsequent infusion doses. The target dose for this study is 4-5x107 cCTL/Kg

Primary outcome measures

• dose-limiting toxicities (DLTs) [Time frame: From Week 1 through Week 16 of treatment]

Secondary outcome measures (5)

• Objective response rate (ORR) [Time frame: Up to Week 16 post-treatment (with imaging assessments up to approximately 12 months or until disease progression)]
• disease control rate (DCR) [Time frame: Up to Week 16 post-treatment (with imaging assessments up to approximately 12 months or until disease progression)]
• Progression-free survival (PFS) [Time frame: Up to approximately 24 months.]
• overall survival (OS) [Time frame: Up to approximately 24 months.]
• duration of response (DOR) [Time frame: Up to approximately 24 months.]

Eligibility criteria

Inclusion criteria

• Age 18 to 65 years (inclusive), male or female;
• Ability to understand the study and has signed the written Informed Consent Form (ICF), and is willing and able to comply with all protocol-required procedures;
• Fresh tumor tissue samples can be obtained via biopsy or surgery, and peripheral blood mononuclear cells (PBMCs) can be obtained via apheresis;
• Histologically and/or cytologically confirmed advanced gastrointestinal solid tumors (e.g., esophageal cancer, gastric cancer, colon cancer, etc.), with previous receipt of at least one systemic therapy that failed or resulted in recurrence; OR previous receipt of any form of immunotherapy or cellular therapy that failed or resulted in recurrence;
• Presence of at least one measurable lesion according to RECIST v1.1, or has an evaluable target lesion/disease assessment method as determined by the investigator. (Note: A measurable lesion is defined as a non-nodal lesion with at least one dimension ≥ 10 mm, or a nodal lesion with a short axis ≥ 15 mm, measured by CT/MRI; lesions previously treated with local therapies \[e.g., radiotherapy\] cannot be considered as target lesions unless clear disease progression is documented.)
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 1;
• Life expectancy ≥ 20 weeks;
• Hepatitis B virus (HBV) infected patients (with HBV DNA levels below the lower limit of detection \[LLOD\]), or cured Hepatitis C virus (HCV) infected patients;
• Laboratory values within 14 days prior to the first dose of study drug must meet the following criteria:

• Hematology: Absolute neutrophil count (ANC) ≥1.5×109/L; Platelets (PLT) ≥100×109/L; Hemoglobin (Hb) ≥90g/L; Note: The above requirements must be met without receiving any transfusion of blood components or supportive therapy with cell growth factors within two weeks prior to blood collection.
• Renal Function: Serum creatinine ≤1.5×upper limit of normal (ULN) OR creatinine clearance (CrCl) ≥50mL/min (calculated using the Cockcroft-Gault formula).
• Hepatic Function: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.0×ULN (for patients with liver metastases, ALT and AST ≤3.0×ULN); Serum total bilirubin (TBIL) ≤1.5×ULN.
• Coagulation Function: International Normalized Ratio (INR) or prothrombin time (PT) ≤1.5×ULN (for patients receiving warfarin anticoagulation, INR must be between 1.5 and 2.5); activated partial thromboplastin time (aPTT) ≤1.5×ULN.
• Female patients of childbearing potential must have a confirmed negative serum pregnancy test within 3 days prior to the first dose of study drug, and must initiate effective contraception immediately following the negative result; patients of childbearing potential and their partners must agree to use highly effective contraception throughout the study drug treatment period and for 90 days after the last dose of study drug.
• Adverse events (AEs) related to prior anti-cancer therapy must have resolved to Grade 0 or 1; the following AEs are permitted for enrollment: alopecia, Grade ≤2 sensory neuropathy, and endocrine disorders controlled by hormone replacement therapy.

Exclusion criteria

• History of a second primary malignancy within 5 years (inclusive) prior to screening, except for cured cervical carcinoma in situ, localized skin squamous cell carcinoma, basal cell carcinoma, ductal carcinoma in situ (DCIS) of the breast, <T1 urothelial carcinoma, or prostate cancer under active surveillance;
• Patients with Gilbert's syndrome;
• Patients with anorexia, nausea, or vomiting of Grade≥2;
• History of bowel obstruction or intestinal perforation within 6 months prior to screening;
• Patients who experienced Grade≥3 toxicity related to prior irinotecan use;
• Symptomatic brain metastases or leptomeningeal metastases; or other evidence indicating that central nervous system (CNS) metastases or leptomeningeal metastases are uncontrolled, and the investigator deems the patient unsuitable for enrollment. Patients with asymptomatic brain metastases or those stable after treatment (receiving≤10mg/day of prednisone or equivalent systemic corticosteroids), with both imaging and neurological examinations judged to be stable following relevant treatment, are permitted to be enrolled;
• History of cerebrovascular accident (CVA), transient ischemic attack (TIA), myocardial infarction (MI), unstable angina, or New York Heart Association (NYHA) Class III or IV heart failure within 24 weeks prior to enrollment; history of malignant arrhythmia within 12 weeks prior to enrollment; or QTcF > 450 ms in males or QTcF > 470 ms in females;
• Active autoimmune disease, or a history of autoimmune disease requiring systemic treatment within 2 years prior to screening. The following conditions are permitted for enrollment: hypothyroidism, vitiligo, Graves' ophthalmopathy, Hashimoto's thyroiditis, Type I diabetes mellitus, childhood asthma, or allergic asthma with no acute exacerbations/attacks within 2 years prior to screening;
• Prior history of allogeneic stem cell transplantation or solid organ transplantation;
• History of severe allergic reactions, Grade 3-4 hypersensitivity to humanized antibody or fusion protein therapies, or known hypersensitivity to irinotecan;
• History of Grade 3-4 immune-related adverse events (irAEs) or those leading to permanent discontinuation of treatment (except for Grade 3 endocrine abnormalities controlled by hormone replacement therapy);
• Receipt of >10mg/day of prednisone (or equivalent systemic corticosteroids) or other immunosuppressants for≥5 consecutive days within 2 weeks prior to screening; however, short-course (≤1 week) of topical, ocular, intra-articular, intranasal, or inhaled administration is permitted;
• Receipt of any live vaccine within 4 weeks prior to enrollment;
• Presence of any of the following: Active bacterial infection requiring intravenous anti-infective therapy within 2 weeks prior to the first dose of study drug; Positive for human immunodeficiency virus (HIV) (HIV-1/2 antibodies); Active tuberculosis (TB) currently receiving anti-TB treatment or having received anti-TB treatment within 1 year prior to screening;
• Receipt of anti-cancer therapy or radiotherapy within 4 weeks or 5 half-lives (whichever is longer) prior to enrollment. Palliative radiotherapy for symptom control is permitted but must be completed at least 2 weeks prior to the first dose of study drug, and no additional radiotherapy is planned for the same lesions;
• Patients who underwent major surgery, interventional therapy/ablation therapy, experienced major trauma within 4 weeks prior to the first dose of study drug, or require elective major surgery during the study period (excluding needle biopsy, aspiration drainage, bronchoscopy, or intravenous cannulation);
• Participation in any drug or medical device clinical trial within 4 weeks prior to the first dose of study drug;
• Presence of psychiatric disorders, psychological illness, or familial genetic diseases that may affect the conduct of the clinical trial;
• According to the investigator's judgment, any condition that may interfere with disease staging, treatment, and follow-up, affect patient compliance, or place the patient at high risk;
• Any other severe underlying diseases or reasons that, in the opinion of the investigator, make the patient unsuitable for participation in the clinical trial.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07735065 · SC2026-0005-02

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗