Phase I/II Clinical Study of GT201 Injection as Monotherapy or in Combination With PD-1 Inhibitor for Advanced Solid Tumors

Phase I/II Clinical Study of Autologous Tumor-Infiltrating Lymphocyte Injection (GT201 Injection) as Monotherapy or in Combination With PD-1 Inhibitor for Advanced Solid Tumors

This is a multicenter Phase I/II clinical trial. It aims to evaluate the safety, tolerability, efficacy and pharmacokinetics (PK) of GT201 in patients with advanced solid tumors.

Inclusion Criteria:

• 1. Voluntarily enroll in the study, sign the informed consent form (ICF), and be willing and able to comply with the study protocol.

• 2. Aged 18 to 70 years old. For subjects older than 70 years old, eligibility shall be jointly determined by the Investigator and the Sponsor's Medical Monitor.

• 3. Diagnosis:

  • Phase I trial: Patients with advanced solid tumors who have failed standard therapy, have no available standard therapy, or cannot tolerate standard therapy.
  • Phase II trial: Patients with the target indication who have progressed or are intolerant after receiving the specified treatment outlined in the protocol, and who meet the inclusion and exclusion criteria for the target indication.

• 4. At least one lesion that is resectable for the preparation of autologous TIL cells.

• 5. At least one measurable lesion that meets the definition of RECIST v1.1 after tumor sampling.

• 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

• 7. Estimated survival time ≥ 12 weeks.

• 8. Functions of major organs meet the requirements specified in the protocol.

• 9. Female or male subjects of childbearing potential who have not undergone surgical sterilization must agree to use at least one medically acceptable contraceptive method (e.g., intrauterine device, oral contraceptives, condoms) during study treatment and for 1 year after the end of study treatment. For female subjects of childbearing potential without surgical sterilization, serum human chorionic gonadotropin (hCG) test must be negative within 7 days prior to cell infusion.

• 10. Prior treatment related adverse events shall have recovered to Grade ≤ 1 per Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 before tumor sampling, or be judged by the investigator together with the sponsor's medical monitor not to interfere with the study.

• 11. For participants enrolled in this study due to disease progression, imaging documentation confirming disease progression following the prior therapy must be available before tumor sampling.

Exclusion Criteria:

• 1. Patients with spinal cord compression not relieved by surgery and/or radiotherapy are excluded. (Patients may be enrolled if clinical evidence confirms symptom relief for ≥ 1 week prior to tumor harvesting.)

• 2. Participants with uncontrolled tumor related pain as judged by the investigator. Participants requiring analgesic medications must have a stable analgesic regimen at study entry. Symptomatic lesions suitable for palliative radiotherapy should have completed treatment prior to study entry.

• 3. Bleeding events within 3 months prior to screening.

• 4. Patients with arterio-venous thrombotic events that occurred within 6 months prior to screening.

• 5. Respiratory disorders that severely impair pulmonary function at screening.

• 6. History of clinically significant cardiovascular disease, including but not limited to:

  1. Congestive heart failure (New York Heart Association [NYHA] Class >grade II);
  2. Unstable angina pectoris;
  3. Myocardial infarction within the previous 3 months;
  4. Any supraventricular or ventricular arrhythmia requiring treatment or intervention.

• 7. Participants with ≥ 3 untreated central nervous system (CNS) metastases.

• 8. Any active autoimmune disease, history of autoimmune disease, or diseases requiring systemic corticosteroids (>10 mg prednisone daily or equivalent) or immunosuppressive agents.

• 9. Malignant tumors other than the target indication within 5 years.

• 10. Presence of intractable epilepsy, medically uncontrolled pleural effusion, ascites, pericardial effusion, or any contraindication to IL-2 administration.

• 11. Active infectious diseases within 1 year prior to screening, such as HIV infection, syphilis, active hepatitis, active pulmonary tuberculosis, active Epstein-Barr virus (EBV) and/or cytomegalovirus (CMV) infection; OR history of active pulmonary tuberculosis infection more than 1 year ago without standard treatment; active hepatitis B or hepatitis C.

  • Participants positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) may enroll if HBV DNA level is below the lower limit of quantification (LLOQ) of the local study laboratory.
  • Participants positive for HCV antibody may enroll if HCV RNA level is below the LLOQ of the local study laboratory.
  • Participants with EBV DNA above the laboratory LLOQ may enroll if the Investigator assesses the viremia is tumor-related and the infection is non-active.
  • Carriers enrolled in the study shall receive antiviral therapy at the Investigator's discretion, with regular quantitative nucleic acid testing scheduled throughout the study period.

• 12. Use of anti angiogenic agents such as bevacizumab within 4 weeks before surgical sampling.

• 13. Previous allogeneic bone marrow transplantation or solid organ transplantation.

• 14. Receipt of systemic anti tumor therapy within 4 weeks prior to lymphodepleting chemotherapy, except for the following:

  • Bridging therapy;
  • If prior chemotherapy with nitrosoureas or mitomycin C was administered, an interval of no less than 6 weeks between the end of such chemotherapy and the anticipated date of lymphodepleting chemotherapy is required for enrolment;
  • If prior small molecule targeted therapy was administered, an interval of no less than 5 half lives of the agent between the end of such therapy and the anticipated date of lymphodepleting chemotherapy is required for enrolment.

• 15. Prior receipt of genetically modified or gene edited cell therapy products (excluding non genetically modified autologous immune cell therapy products administered more than 1 year before the date of cell infusion).

• 16. History of hypersensitivity reaction to any component of investigational products to be used in the study, including but not limited to autologous TIL, cyclophosphamide, fludarabine, IL-2, dimethyl sulfoxide (DMSO), human serum albumin (HSA), dextran 40, antibiotics (β-lactam antibiotics, gentamicin).

• 17. Known psychiatric illness, alcoholism, drug addiction or substance abuse.

• 18. Prior immune therapy related adverse events of Grade 3 or higher that have not recovered to CTCAE Grade 1 or less within 28 days; or any other disease or medical condition (any other illness, metabolic disorder, physical finding abnormality or laboratory abnormality) that would raise reasonable concerns prohibiting the use of investigational product, confound the interpretation of study results, or place the participant at high risk of treatment related complications.

• 19. Pregnant or lactating women; or women with plans for pregnancy, conception or lactation within 1 year after the end of study treatment.

• 20. Receipt of other investigational medicinal products within 4 weeks prior to lymphodepleting chemotherapy, or plan to receive other investigational medicinal products during the study.

• 21. Other conditions deemed ineligible for enrollment at the investigator's discretion.