A Clinical Study GK01 Injection in Subjects With Advanced Malignant Solid Tumors

A Phase I, Open-label, Single-arm Clinical Study of GK01 Cell Injection in Patients With Advanced Malignant Solid Tumors

An Open-label, Single-arm, Phase I Clinical Study of GK01 Cell Injection in the Treatment of Patients with Advanced Malignant Solid Tumors

Inclusion Criteria:

1. Understanding and voluntarily signing the Informed Consent Form (ICF) prior to any study-related assessments/procedures;
2. Aged 18 to 70 years old (inclusive) at the time of signing the ICF;
3. Patients with histologically or cytologically confirmed advanced solid tumors (including but not limited to advanced gastric cancer, non-small cell lung cancer, etc.), who have progressed upon the standard of care (SoC), do not tolerate the SoC, or have no SoC;
4. At least one resectable tumor lesion that has not been treated with radiation therapy or other topical therapy, and tissue blocks with the total sum of diameter of resected lesions being 1.5-4 cm or weighing ≥ 1.0 g (sourced from a single lesion or multiple lesions) are available for preparation of autologous tumor-infiltrating lymphocytes;
5. At least 1 measurable lesion (as per RECIST1.1 criteria) even after biopsy for tumor tissue sampling;
6. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 at the time of signing the ICF;
7. Estimated life expectancy> 3 months;
8. Adequate hematological and organ reserve functions;
9. Men of reproductive potential and women of child-bearing potential must agree to use effective contraception from the signing of ICF utill 2 years after the end of study treatment. Women of childbearing potential include pre-menopausal women and those within 2 years after menopause. Women of childbearing potential must have negative serum pregnancy test results at screening.
10. No absolute or relative contraindications to surgery;
11. Any therapy for malignant tumors, including radiotherapy, chemotherapy, endocrine therapy, targeted therapy, tumor embolization, or traditional Chinese medicine/herbal therapy with antitumor indications, must be discontinued 14 days prior to tumor tissue sampling;
12. Volunteering to sign the written ICF, having good compliance, and being able to follow the protocol-specified visits or unscheduled visits and other relevant study procedures.

Exclusion Criteria:

1. History of serious allergy, or hypersensitivity to any ingredients of the drug to be used in this study, including but not limited to lymphodepleting agents (nab-paclitaxel, cyclophosphamide, fludarabine), contrast agents for imaging examination, contrast media, and GK01 excipients (e.g., dimethyl sulfoxide, etc.);
2. Use of any investigational drug or systemic anti-tumor therapy (except lymphodepleting conditioning regimen) within 28 days (or 5 half-lives of the drug, whichever is more appropriate at the discretion of the investigator) prior to reinfusion;
3. Participation in any clinical trial of biological therapy (except for cell therapy that has been fully metabolized) within 28 days prior to the signing of ICF;
4. Use of extensive radiotherapy within 28 days prior to the signing of ICF, with the exception of topical radiotherapy to non-target lesion(s) that has been administered within 14 days prior to the signing of ICF or is expected to be administered during the study for symptom relief;
5. Major surgery within 28 days prior to the signing of ICF, or planned major surgery during the study period;
6. Toxicities caused by previous anti-tumor therapy, except for alopecia and pigmentation, have not resolved to grade 1 or baseline level (as per NCI-CTCAE Version 6.0) at the time of signing ICF;
7. Any uncontrolled active infection requiring parenteral antibiotic, antiviral, or antifungal treatment at the time of signing the ICF or within 4 weeks prior to the first reinfusion;
8. Subjects with active autoimmune disorders, or history of autoimmune disorders that may relapse (including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vasculitis, psoriasis, etc.), or at risk of such diseases;
9. A history of previous bone marrow or organ transplantation;
10. Concomitant or history of interstitial lung disease or interstitial pneumonia;
11. History of active pulmonary tuberculosis within 1 year before screening (excluding subjects with a history of active pulmonary tuberculosis infection more than 1 year ago, who have no evidence of active pulmonary tuberculosis as determined by the investigators at present);
12. History of other primary malignancy within 5 years prior to study treatment
13. Clinically significant cardiovascular diseases; significant, obvious risk or tendency of bleeding (any grade ≥ 3 bleeding or hemorrhage events within 28 days prior to screening, including esophageal variceal bleeding);

15) Metabolic disorders, such as poorly controlled diabetes mellitus (HbA1c ≥ 8.5%) or other non-malignant organ or systemic diseases or secondary reactions to cancer, which may lead to a higher medical risk and/or uncertainty in survival evaluation; 16) Central nervous system (CNS) metastases, leptomeningeal disease, or metastatic CNS compression; or history of CNS diseases, including but not limited to epilepsy, paralysis, aphasia, stroke, serious brain injury, dementia, Parkinson's disease, etc.; 17) Immunization with attenuated/inactivated vaccine within 28 days prior to the signing of ICF, or planning to receive immunization with attenuated/inactivated vaccine during the screening period; 18) Subjects who need to receive systemic corticosteroids at a dose equivalent to or higher than 10 mg/day of prednisone or other immunosuppressive drugs within 14 days before tumor tissue sampling or during the study period； 19) At screening, subjects who are tested positive for hepatitis B surface antigen (HBsAg) should be excluded; if HBsAg is negative but hepatitis B core antibody (HBcAb) is positive, subjects with hepatitis B virus (HBV) DNA above the lower limit of detection in peripheral blood should be excluded; subjects with positive hepatitis C virus (HCV) antibody, human immunodeficiency virus (HIV) antibody positive, or both Treponema pallidum-specific and unspecific antibodies positive should also be excluded; 20) Pregnant or lactating women; 21) Presence of complications or other conditions that, in the investigator's opinion, could compromise compliance with the protocol or make the subject otherwise unsuitable for the study.