Single Arm Phase I Trail of Autologous Tumor Infiltrating Lymphocyte Injection (GT202) in the Treatment of Metastatic or Recurrent Gynecological Tumors

Overview

A prospective, open-label, non-randomized, Phase 1 study evaluating autologous tumor infiltrating lymphocyte injection (GT202) in the treatment of metastatic or recurrent Gynecological tumors.

Eligibility

Inclusion Criteria:

• 1. Voluntary participation and sign informed consent
• 2.Must be ≥ 18 and ≤70 years at the time of consent
• 3.Must be diagnosis of unresectable Metastatic or Recurrent Gynecological Tumors (limited to cervical cancer, ovarian cancer and endometrial cancer)
• 4.Must have progressed following at least one line of standard treatment, and there is no alternative effective treatment or alternative effective treatment plan rejected by patient (effective treatment refers to the latest version of diagnosis and treatment guidelines for various cancers)
• 5.At least one resectable lesion (or invaded superficial lymph nodes, or aggregate of lesions resected) of a minimum 0.5cm3 for resection to generate TIL. Minimally invasive surgery is preferred. This lesion cannot be in previously irradiated areas or other local therapy.
• 6.At least one another measurable target lesion after resection, as defined by RECIST v1.1. Lesions in previously irradiated areas (or other local therapy) should not be selected as target lesions, unless treatment was ≥ 3 months prior to screening, and there has been demonstrated disease progression in that particular lesion.
• 7.ECOG=0 or 1
• 8.Estimated life expectancy of ≥ 12 weeks
• 9.Patients must have adequate organ function:
  1. hematologic parameters: Absolute neutrophil count (ANC) ≥ 1.5×109/L Lymphocyte counts（LC）>0.5×109/L Platelet ≥100×109/L Hemoglobin (Hb) ≥ 90g/L
  2. AST, ALT and alkaline phosphatase ≤ 2.5 times the upper limit of normal (ULN), TBIL (total bilirubin)≤1.5×ULN, except following:

        patients with liver metastasis: AST, ALT≤ 5 times ULN; Patients with liver metastasis or
        bone metastasis: alkaline phosphatase≤5 times ULN; Patients with Gilbert syndrome: TBIL≤3.0
        mg/dL; Estimated creatinine clearance (eCrCl) ≥ 45 mL/min using the Cockcroft-Gault
        formula, or serum creatinine in normal range; d) APTT≤1.5×ULN, while INR or PT≤1.5×ULN; e)
        LVEF ≥50%; f) FEV1≥60%;
          -  10.Patients of childbearing potential or their partners of childbearing potential must
             be willing to take the appropriate precaution to avoid pregnancy or fathering a child
             for the duration of the study and practice an approved, highly effective method of
             birth control during treatment and for 12 months after receiving the last
             protocol-related therapy. Non surgically sterilized female subjects of reproductive
             age must be negative for serum hCG testing within 7 days prior to cell infusion;
          -  11.Patients must have recovered from all prior therapy-related adverse events (AEs) to
             ≤ Grade 1 (per Common Terminology Criteria for Adverse Events [CTCAE] v5.0), except
             for alopecia or vitiligo, prior to enrollment (tumor resection). Patients with
             documented ≥ Grade 2 diarrhea or colitis as a result of previous treatment with immune
             checkpoint inhibitor(s) must have been asymptomatic for at least 6 months and/or had a
             normal colonoscopy post-immune checkpoint inhibitor treatment, by visual assessment,
             prior to tumor resection;
          -  12.Before resection, the imaging evidence of disease progress after prior line
             treatment should be documented.
        Exclusion Criteria:
          -  1. Patients with symptomatic and/or untreated CNS metastases (Patients with
             definitively treated brain metastases may be considered for enrollment and must be
             stable for ≥ 14 days without drug treatment and steroid-dependent) ;
          -  2. Failure of surgery and / or radiotherapy to relieve spinal cord compression;
          -  3. Uncontrolled tumor related pain judged by the investigator. Subjects requiring pain
             medication must have had a stable pain medication regimen at the time of enrollment;
             symptomatic lesions amenable to palliative radiotherapy should have completed
             treatment before enrollment;
          -  4. Interstitial pneumonia or clinically significant active pneumonia, or other
             respiratory disease severely affecting lung function;
          -  5. Any active autoimmune disease; a history of autoimmune disease or disease requiring
             treatment with systemic steroids or immunosuppressive drugs;
          -  6. Patients with a history of significant cardiovascular disease, including: 1)
             Congestive heart failure (NYHA functional classification > Class 2); 2) Unstable
             angina; 3) myocardial infarction occurred in past 3 months; 4) Any supraventricular
             arrhythmia or ventricular arrhythmia requiring treatment or intervention;
          -  7. Arterial/venous thrombotic events within 5 months prior to enrollment, such as:
             cerebrovascular accident, deep vein thrombosis and pulmonary embolism occurring;
          -  8. Patients with active tuberculosis infection within 1 year before enrollment, or
             with a history of active tuberculosis infection beyond 1 year before but without
             standard treatment;
          -  9. Active infections requiring treatment with systemic anti-infectives (except for
             topical antibiotics); or those with unexplained fever > 38.5℃ occurring during the
             screening period, except for tumor fever;
          -  10. Patients with a history of immunodeficiency, including HIV seropositivity;
          -  11. Patients with active hepatitis B or C. Patients with seropositive HBsAg or HBcAb
             can be enrolled while negative HBV DNA. Patients with seropositive HCV antibody can be
             enrolled while negative HCV RNA. If potential carriers enrolled, proper anti-virus
             treatment and regular nucleotide test should be arranged.
          -  12. Patients with intractable or intractable epilepsy, ascites beyond drug control,
             portal vein tumor thrombus, gastrointestinal bleeding caused by gastric fundus or
             esophageal varices, increased risk of bleeding caused by portal hypertension, and
             active gastrointestinal bleeding
          -  13. Patients who have received an organ allograft or prior cell transfer therapy;
          -  14. Patients who have a history of hypersensitivity to any component or excipient of
             GT202 or other study drugs: autologous tumor infiltrating lymphocytes,
             cyclophosphamide, fludarabine, IL-2, dimethyl sulfoxide (DMSO), human serum albumin
             (HSA), dextran-40 and antibiotics (beta lactam antibiotics, gentamicin);
          -  15. Known psychiatric disorders, alcohol, drug or substance abuse;
          -  16. Any disease or condition (any other condition, metabolic disorder, physical exam
             result, or abnormal laboratory test result) that could lead to reasonable doubt that
             would prohibit the use of a trial drug, or affect the interpretation of study results,
             or put the patient at high-risk treatment;
          -  17. Patients who are pregnant or breastfeeding;
          -  18. Other circumstances that investigator assessed could affect the safety of
             subjects.