Advanced Solid Tumors
Conditions
Brief summary
A Single-Center, Open-Label Clinical Study to Evaluate the Safety, Preliminary Efficacy of GK01 Cell Injection in Subjects with Advanced Solid Tumors Refractory or Intolerant to Standard Therapy
Interventions
DRUGGK01 Injection
Autologous tumor-reactive T cells injection
Sponsors
Beijing Geekgene Technology Co., LTD
The First Affiliated Hospital of Nanchang University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Ability to understand and sign a written informed consent document. * At the date of signing ICF, 18 \~75 years old, male or female. * Advanced lung cancer or esophageal squamous cell carcinoma confirmed by cytology or histopathology, failed or intolerant to standard therapy. * At least one measurable lesion that has not been irradiated or received other local therapies. * At least one measurable lesion remains (RECIST 1.1 criteria). * ECOG 0-1 points. * Expected survival time more than 3 months. * Adequate hematologic and organ function. * No absolute or relative contraindications to surgery, bronchoscopy, or percutaneous procedures.
Exclusion criteria
* History of severe allergy, or hypersensitivity to any component of the drugs used in this study, including but not limited to lymphodepleting chemotherapy drugs, contrast agents for radiological examinations, and excipients of GK01 (such as dimethyl sulfoxide). * Any investigational drug or systemic anti-tumor therapy within 28 days prior to the start of lymphodepleting chemotherapy preconditioning, or within 5 half-lives of the previous drug. * Major surgery within 28 days prior to signing the ICF, or planned during the study period. * Toxicities from previous anti-tumor therapies have not recovered to ≤ Grade 1 or baseline level (according to NCI-CTCAE version 5.0) at the time of signing the ICF, with the exception of alopecia and hyperpigmentation. * Any uncontrolled active infection requiring parenteral antibiotic, antiviral, or antifungal therapy within 4 weeks prior to signing the ICF or before the first infusion. * History of or current active autoimmune disease that has the potential to recur (including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vasculitis, psoriasis, etc.), or subjects at such risk. * Prior history of bone marrow or organ transplantation. * Concurrent or prior history of interstitial lung disease or interstitial pneumonia. * History of active tuberculosis infection within 1 year prior to screening (subjects with a history of active tuberculosis infection more than 1 year ago may be enrolled if the investigator confirms there is no current evidence of active tuberculosis). * History of other primary malignancies within 5 years prior to the initiation of the study treatment. * Clinically significant cardiovascular disease. * History of bleeding within 6 months prior to signing the ICF. * Metabolic disorders, such as diabetes mellitus (with glycated hemoglobin \[HbA1c\] ≥8.5%), or other non-malignant organ or systemic diseases, or secondary reactions to cancer that may lead to high medical risk and/or uncertainty in survival assessment. * Central nervous system (CNS) metastases, leptomeningeal disease, or metastatic spinal cord compression; or a history of CNS disorders. * Live/attenuated or inactivated vaccine within 28 days prior to signing the ICF, or planned administration of a live/attenuated or inactivated vaccine during the screening period. * Systemic corticosteroid therapy (at a dose equivalent to or greater than 10 mg/day of prednisone) or other immunosuppressive medications within 14 days prior to tissue acquisition or during the study period. * Hepatitis B surface antigen (HBsAg) positivity; With negative HBsAg positive hepatitis B core antibody (HBcAb) ,and if peripheral blood hepatitis B virus (HBV) DNA positive; Hepatitis C virus (HCV) antibody positive and HCV RNA positive; Human immunodeficiency virus (HIV) antibody positive; Cytomegalovirus (CMV) DNA positive; Both Treponema pallidum-specific and non-specific antibody tests are positive. * Female subjects who are pregnant or breastfeeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability | 2 years | The incidence and severity, and correlation of AEs (Adverse Events) and SAEs (Serious Adverse Events) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Count of TCR copies | 2 years | T-cell receptor sequencing (TCR-seq) by obtaining the copy number of the target GK02 T-cell receptors (TCRs) in peripheral blood：Cmax、Tmax、AUC0-t、AUC0-inf、λz、T1/2. |
| Concentration of Cytokines | 2 years | IL-1β、IL-2、IL-4、IL-6、IL-8、TGF-b1、IFN-γ and TNF-α |
| Percentage of Lymphocyte subsets | 2 years | Total T cells、Th/Ti cells、Ts/Tc cells、NK cells |
| Circulating tumor DNA | 2 years | The time between Circulating tumor DNA (ctDNA) positivity and Clinical Progression |
| Objective response rate (ORR) | 2 years | Proportion of subjects achieving complete response (CR) and partial response (PR) |
| Progression-free Survival (PFS) | 2 years | Time from GK01 treatment to disease progression or death |
| Disease Control Rate (DCR) | 2 years | Proportion of subjects achieving best response of CR, PR, or SD treated with GK01 |
| Duration of Response (DOR) | 2 years | Time from first documented evidence of confirmed CR or PR until the first documented evidence of disease progression or death, whichever occurs earlier |
| Overall survival (OS) | 2 years | Time from GK01 treatment to death |
Countries
China
Contacts
CONTACTBenTong Yu, MD
CONTACTXu Zhang, PhD
Outcome results
None listed