a Single-arm, Single-center, Open Clinical Study

NCT06431100 | Recruiting

• 1 other identifier: GK-01
• Study Type: observational
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This trial plans to enroll many patients with advanced solid tumors to complete GK01 cell transfusion, including but not limited to advanced gastric cancer, esophageal cancer, cervical cancer, triple-negative breast cancer, and non-small cell lung cancer. For patients with advanced solid tumors eligible for inclusion, autologous tumor-reactive T cells (experimental drug GK01) were cultured and prepared, and a certain dose of GK01 cells was given according to the cell transfusion plan, and the safety and tolerability of the patients after transfusion were observed. Exploratory evaluation of pharmacokinetic/pharmacodynamic profiles following reinfusion and initial evaluation of efficacy of investigational drug GK01 cells according to RECIST 1.1 criteria.

Conditions

Gastric Cancer; Esophageal Cancer; Cervical Cancer; Non-Small Cell Lung Cancer NSCLC; Triple Negative Breast Cancer TNBC

Keywords

TRT; cell therapy; advanced tumor; safety; efficiency; adverse event

Outcome Measures

Primary Outcomes (1)

• safety and tolerability

  To evaluate the safety and tolerability of GK01 autologous tumor-reactive T cells (TRT) in patients with advanced solid tumors.

  From enrollment to the end of follow-up visit at 22weaks or more

Secondary Outcomes (2)

• specificity and persistence

  From enrollment to the end of treatment at 28 days

• initial efficacy

  From enrollment to the end of treatment at 28 days

Study Arms (1)

cell therapy interventional single arm

According to the cell transfusion protocol, GK01 cells were given at a certain dose level to observe the safety and tolerability of the patients after the transfusion, explore the pharmacokinetic/pharmacodynamic characteristics after the transfusion, and preliminarily evaluate the effectiveness of the experimental drug GK01 cells according to the RECIST 1.1 standard.

Biological: TCR T-cells

Interventions

TCR T-cells BIOLOGICAL

The strengthened T cells are re-infused into the patient to achieve the killing effect

cell therapy interventional single arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

GK01 cell transfusions were performed in 10 patients with advanced solid tumors, including but not limited to advanced non-small cell lung cancer, gastric cancer, and esophageal cancer.

You may qualify if:

• Participants who meet all of the following criteria are eligible for admission to the study:
• ≤ age ≤75 years old, male or female;
• Patients with incurable advanced gastric cancer, esophageal cancer, cervical cancer, triple-negative breast cancer, non-small cell lung cancer, and other malignancies who have failed standard treatment (standard treatment failure is defined as those treated according to the 2022 CSCO Guidelines and whose tumor efficacy is assessed as disease progression (PD) or tumor recurrence or inability to tolerate existing treatment options);
• There are tumor tissues or cancerous exudative thoracoabdominal fluid that can be used to isolate TRTs: the total volume of the solid tissue taken must be \> 0.5cm3 or the weight must be \>0.5g, the cancerous exudative thoracoabdominal fluid taken should contain at least 5×10\^8 total cells, and the lesions taken have not been treated with oncolytic virus.
• There is at least one measurable lesion (according to RECIST1.1 criteria) even after TRTs sampling/puncture biopsy;
• ECOG score 0-1;
• The expected survival period is greater than 3 months;
• Sufficient hematology and end-organ function, as defined by the following laboratory test results, should be completed within 14 days prior to TRTs tumor tissue collection:
• Blood routine: white blood cell count ≥2.5×10\^9/L; Absolute neutrophil count (ANC) ≥1.5×10\^9/L; Absolute lymphocyte count (ALC) ≥1.0×10\^9/L; Platelet (PLT) ≥80×10\^9/L; Hemoglobin (HGB) ≥90g/L;
• Coagulation function: International standardized ratio of prothrombin time (INR) ≤1.5×ULN; Partial prothrombin time (APTT) ≤1.5×ULN, unless anticoagulant therapy has been received within the previous 7 days;
• Renal function: serum creatinine ≤1.5mg/dL (or 132.6μmol/L) or creatinine clearance ≥60mL/ min;
• Liver function: aspartate aminotransferase (AST/SGOT) ≤3×ULN; Alanine transaminase (ALT/SGPT) ≤3×ULN; Total bilirubin (TBIL) ≤1.5×ULN; Note: In patients with liver metastasis or primary liver tumor, aspartate and alanine aminotransferase should be ≤5×ULN; For patients with a history of Gilbert syndrome or suspected Gilbert syndrome, total bilirubin (TBIL) should be ≤3×ULN;
• Urine routine: urinary protein \<2+, or 24-hour urinary protein quantity \<1g;
• Left ventricular ejection fraction (LVEF) ≥50% by echocardiography;
• Pulmonary function tests with FEV1\>60% or FEV1/FVC\>0.7;

You may not qualify if:

• Subjects who meet any of the following criteria will not be eligible to participate in this clinical trial:
• Prior allergy to cyclophosphamide, fludarabine and interleukin-2 contraindications or to any component of the infusion product formulation or to other drugs to be used during the study (antibiotics, human serum albumin, dextran 40, etc.);
• Any NCI CTCAE5.0 immune-related adverse reaction (irAE) grade \>3 that has been permanently discontinued during any previous immunotherapy;
• Patients with prior primary immunodeficiency and active autoimmune disease;
• Previous history of organ allotransplantation, allogeneic stem cell transplantation and kidney replacement therapy;
• Patients with current or past irreversible interstitial lung disease (except those caused by radiotherapy);
• Combined with 2 or more malignant tumors; (Except for the following cases: malignant tumors that have been cured, such as non-melanoma skin cancer and in situ cervical cancer, bladder cancer, breast cancer, thyroid cancer, etc. that have survived more than 5 years without disease.)
• Uncontrolled co-morbidity includes, but is not limited to, uncontrolled hypertension (systolic blood pressure ≥160mmHg and/or diastolic blood pressure ≥100mmHg) even after standard treatment, or any unstable cardiovascular and cerebrovascular disease, including transient ischemic attack, cerebrovascular accident, myocardial infarction, and unstable angina pectoral, that has occurred in the 6 months prior to treatment induction; Congestive heart failure rated III or IV by the New York Heart Association (NYHA); Ejection fraction \< 50%; Severe heart rhythm or conduction abnormalities, such as ventricular arrhythmias requiring clinical intervention, degree II-III atrioventricular block, etc. Electrocardiogram results show clinically significant abnormalities, or QTcF≥450ms (if the first examination is abnormal, the interval of at least 5 minutes, retest twice, using the comprehensive result/average value to judge eligibility);
• Patients with esophageal or gastric varices that require immediate intervention (such as ligation or sclerotherapy) or are considered by the investigator or gastroenterologist or hepatologist to be at high risk of bleeding, have evidence of portal hypertension (including splenomegalysis on imaging), or have a history of varicose bleeding must undergo endoscopic evaluation within 3 months prior to enrollment;
• Uncontrolled metabolic disorders, such as in patients with diabetes, or other non-malignant organ or systemic disease or cancer secondary reactions that can lead to higher medical risk and/or uncertainty in the evaluation of survival;
• Hepatic encephalopathy, hepatorenal syndrome or Child-Pugh grade C or more severe cirrhosis, liver failure;
• Clinically uncontrollable third space effusion, such as pleural fluid and ascites that could not be controlled by drainage or other methods before enrollment;
• Combined with other serious organic disease or mental illness;
• Patients with central nervous system metastasis;
• Uncontrolled systemic active infection;

Sponsors & Collaborators

• Beijing Geekgene Technology Co., LTD: lead

Study Sites (1)

First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, 450052, China

RECRUITING

MeSH Terms

Conditions

Stomach Neoplasms; Esophageal Neoplasms; Uterine Cervical Neoplasms

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Head and Neck Neoplasms; Esophageal Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Central Study Contacts

Yi Zhang, Doctor

CONTACT

86+15138928971; yizhang@zzu.edu.cn

Ge Zhang

CONTACT

0086+13633861412; zhangg@geekgene.cn

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Target Duration: 36 Months
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 20, 2024
• First Posted: May 28, 2024
• Study Start: July 19, 2023
• Primary Completion (Estimated): July 19, 2026
• Study Completion (Estimated): November 19, 2026
• Last Updated: May 28, 2024

Record last verified: 2024-05

Locations

CN (1)