A Phase I Trial of Tumor-Associated Lymph Node T-Cell Injection With Advanced Malignant Solid Tumors

A Phase I Clinical Trial of the Safety and Tolerability of Tumor-Associated Lymph Node T-Cell Injection (TAL-T) in Subjects With Advanced Malignant Solid Tumors

A Phase I clinical trial of the safety and tolerability of tumor-associated lymph node T cell injection in patients with advanced malignant solid tumors, including but not limited to melanoma, head and neck tumors, cervical cancer, and non-small cell lung cancer.

The study was divided into two phases, the dose-range exploration study and the expanded enrollment study.

Exploration of the dosage range phase and the expanded enrollment phase were designed to evaluate the safety, tolerability, and initial efficacy of TAL-T cell therapy in patients with advanced solid tumors

Inclusion Criteria:

1. Sign a written informed consent (ICF) and be able to comply with the visit and related procedures required by the program;

2. Age ≥18 years old, and ≤75 years old, male and female;

3. ECOG score 0-1;

4. Expected survival is not less than 12 weeks;

5. Advanced malignant solid tumors confirmed by cytology or histopathology (tumor markers combined with imaging can be used for some special advanced tumors, such as liver cancer) that have failed standard treatment or lack effective treatment methods, including but not limited to melanoma, head and neck tumors, cervical cancer, non-small cell lung cancer, etc.

   "Standard treatment failure" refers to the occurrence of disease progression after enough treatment courses and sufficient lines of treatment with the existing standard recommended therapy (refer to the latest CSCO guidelines), or recurrence after the regression of the tumor after standard treatment, or the toxic side effects of standard treatment are not tolerated.

6. There are tumor-associated lymph nodes that can be resected and T cells can be isolated: the tissue taken is ≥1 cm3, and the site has not received local treatment or has progressed after local treatment;

7. After sampling, subjects still have at least one evaluable lesion (Extended enrollment phase according to RECIST v1.1, subjects still have at least one measurable lesion (lesions that have received local treatment such as radiotherapy, interventional therapy, etc., cannot be considered as measurable lesions unless imaging evidence confirms clear progression of the lesion). That is, CT or MRI examination of non-lymph node lesions with the longest diameter ≥10 mm, and/or lymph node lesions with a short diameter ≥15 mm);

8. The subject has sufficient organ and bone marrow function (no blood transfusion or hematopoietic stimulating factors can be received within 14 days prior to screening)

9. Fertile men and women of reproductive age must agree to use effective contraception from the time they sign the ICF until one year after cell transfusion, and women of reproductive age must have a negative blood pregnancy test at the time of screening.

Exclusion Criteria:

1. meningeal metastases, and/or active brain metastases;
2. Have previously received allogeneic bone marrow transplantation, organ transplantation or are waiting for transplantation;
3. HBsAg positive hepatitis B; HCV-Ab positive hepatitis C; Positive for human immunodeficiency virus (HIV) antibodies; Syphilis antibody positive; Cytomegalovirus (CMV) IgM antibody positive; Human herpesvirus type 4 (EBV) IgM positive; Human T-lymphocytophilic virus (HTLV-Ⅰ/Ⅱ) antibody positive;
4. Received any fluorouracil chemotherapeutic drugs or small molecule targeted drugs within 14 days or 5 half-lives (whichever is shorter) prior to pretreatment; Received any antitumor biologic or non-fluorouracil chemotherapeutic drugs within 28 days or 5 half-lives (whichever is shorter) prior to pretreatment; Received radical radiotherapy or extensive radiotherapy within 28 days prior to pretreatment (except local non-target palliative radiotherapy for symptom relief within 14 days prior to pretreatment); Received Chinese medicine/Chinese herbal medicine with anti-tumor indications and local interventional therapy within 14 days prior to pretreatment;
5. Adverse events resulting from previous antitumor therapy have not returned to grade 1 or baseline levels (except for alopecia, grade 2 peripheral neurotoxicity, hypothyroidism controlled by alternative therapy and other toxicities that the investigators judged to be of no safety risk);
6. Persons who had been immunized with live attenuated vaccine within 28 days prior to pretreatment, or who required live attenuated vaccine immunization during the study period;
7. Had major surgery within 28 days prior to pretreatment, or required major surgery during the study period;
8. Long-term (≥3 days) treatment with systemic corticosteroids (dose ≥10 mg/ day of prednisone or equivalent hormone) or other immunosuppressive agents, except for inhalation or local use, is required 7 days before the tumor-associated lymph node excision sampling or during the study period;
9. Subjects with active systemic infections requiring intravenous antibiotic treatment within 7 days prior to screening;
10. Patients with active or past autoimmune diseases that are likely to recurs, such as systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vasculitis, psoriasis, etc. (subjects with hypothyroidism requiring only thyroid hormone replacement therapy, and subjects with type 1 diabetes requiring only insulin replacement therapy can be enrolled);
11. Previous or current cases of interstitial lung disease, coniosis, radiation pneumonia, severe impairment of lung function, etc.;
12. Hepatic encephalopathy, hepatorenal syndrome or Child-Pugh grade B or more severe cirrhosis, liver failure;
13. Third space effusion with poor clinical control before screening, such as pleural fluid and ascites that cannot be controlled by drainage or other methods;
14. Have a history of severe cardiovascular and cerebrovascular disease
15. Patients with pulmonary embolism or severe deep venous thrombosis of lower extremities during screening, requiring interventional therapy such as inferior vena cava filter placement, or using therapeutic dose of anticoagulants;
16. Any CTCAE 5.0 immune-related adverse reactions (irAE) grade ≥3 during any prior immunotherapy;
17. Those with immune checkpoints (such as PD-1) for treatment of other contraindications;
18. Subjects are participating in other interventional clinical studies;
19. Pregnant or lactating women;
20. The investigator believes that the subjects have other conditions that may affect their compliance or are not suitable to participate in the study.