Clinical Trial of TQB2618 Injection Combined With TQB2450 Injection in Patients With Advanced Solid Tumors

Inclusion Criteria:

* The subjects voluntarily participated the study and signed the informed consent form;
* Age: 18\~75 years old (when signing the informed consent form); ECOG PS score: 0\~1 points; Expected survival is more than 3 months;
* The enrolled patients meet the following criteria:

  1. Satge I (dose exploration): patients with advanced malignant solid tumors confirmed by tissue and/or cytology, where standard therapy has failed or there is a lack of effective treatment;
  2. Stage 2 (cohort Expansion):

     1. Cohort 1: PD-L1-positive patients with advanced first-line NSCLC;
     2. Cohort 2: PD-L1 positive patients with advanced immunoresistant NSCLC;

        1. Patients with locally advanced (stage III.B/III.C), recurrent or metastatic (stage IV) NSCLC who are not histologically or cytologically confirmed and are not suitable for radical concurrent chemoradiotherapy.
        2. For non-squamous non-small cell lung cancer, the test proves the absence of EGFR mutation, ALK fusion, ROS1 mutation (for squamous non-small cell lung cancer, patients with known mutations in the above genes are excluded, and testing is not mandatory for those whose status is unknown);
        3. Positive PD-L1 expression ratio≥1% \[TC (tumor cells) or IC (immune cells) ≥1%\];
        4. Cohort 1 advanced first-line patients: no systemic antitumor therapy for advanced disease.
        5. Patients with advanced immunoresistance in cohort 2: at least prior failure of platinum-containing chemotherapy and immune checkpoint inhibitor (PD-1 or PD-L1) therapy (combined or sequential therapy allowed)
* at least one measurable lesion confirmed according to RECIST 1.1;
* The main organs function normally
* Female subjects of childbearing age should agree that contraception must be used during the study and for 6 months after the end of the study

Exclusion Criteria:

* Comorbidities and medical history:

  1. Have received chemotherapy within 3 weeks before the first dose, radiotherapy (except palliative radiotherapy for non-target lesions) or other antineoplastic drugs within 2 weeks before the first dose (the washout period is calculated from the end of the last treatment);
  2. Have developed or are currently suffering from other malignant tumors within 3 years before the first dose. The following two conditions can be enrolled: other malignancies treated with a single surgery, achieving 5 consecutive years of disease-free survival (DFS); cured carcinoma in situ, non-melanoma skin cancer, and superficial bladder tumors \[Ta (non-invasive tumor), Tis (carcinoma in situ), and T1 (tumor-invasive basement membrane)\];
  3. unresolved toxicities above CTC AE grade 1 due to any prior treatment, excluding hair loss;
  4. Major surgical treatment and obvious traumatic injury within 28 days before the first dose;
  5. Wounds or fractures that have not healed for a long time;
  6. Arterioven/venous thrombotic events within 6 months prior to the first dose;
  7. Those with a history of psychotropic substance abuse and cannot quit or have mental disorders;
  8. Subjects with any severe and/or uncontrolled disease.
* Tumor-related symptoms and treatment:

  1. Received proprietary Chinese medicine treatment with anti-tumor indications specified in the NMPA-approved drug instructions within 2 weeks before the first dose;
  2. Have received previous anti-TIM-3 antibody treatment;
  3. Have received previous immunotherapy drugs such as anti-PD-1/PD-L1 antibody and anti-CTLA-4 antibody (only applicable to cohort 1 of the Stage II cohort expansion study: advanced first-line NSCLC patients with positive PD-L1 expression);
  4. uncontrolled pleural effusion, pericardial effusion, or ascites that still requires repeated drainage (judged by the investigator);
  5. Known spinal cord compression, cancerous meningitis, with symptoms of brain metastases or symptom control for less than 2 weeks;
* Study treatment-related:

  1. History of live attenuated vaccination within 28 days before the first dose or planned live attenuated vaccination during the study period;
  2. Those who have severe hypersensitivity reactions after using macromolecular drugs;
  3. Active autoimmune disease requiring systemic therapy within 2 years before the first dose (e.g., use of disease-modifying drugs, corticosteroids, or immunosuppressants); asthma patients requiring bronchodilators for medical intervention.
* Those who have participated in and used other anti-tumor clinical trial drugs within 4 weeks before the first dose;