Clinical Trial of TQB2868 Injection in Subjects With Advanced Malignant Tumors

Phase I Clinical Trial to Evaluate the Tolerability and Pharmacokinetics of TQB2868 Injection in Subjects With Advanced Malignant Tumors

The TQB2868 protein in this study targeted programmed cell death protein 1 (PD-1) and transforming growth factor-β (TGF-β). The bifunctional fusion protein targets and neutralizes TGF-β in the tumor microenvironment. On the basis of inhibiting PD-1 / programmed death ligand 1 (PD-L1) pathway, T cells can restore activity, enhance immune response, and more effectively improve the effect of inhibiting tumor occurrence and development.

Inclusion Criteria:

• 1 Subjects voluntarily join the study and sign an informed consent form.
• 2 Age: 18-75 years old (when signing the informed consent form); Eastern Cooperative Oncology Group Performance status (ECOG PS) score: 0~1 points.
• 3 Advanced malignant tumors clearly diagnosed by histology or cytology.
• 4 Patients with advanced malignant tumors who have been diagnosed by tissue and/or cytology and have failed standard treatments or lack effective treatment options.
• 5 The main organs are in good function, and the following examination results are good: routine blood examination, biochemical examination, blood coagulation function examination, heart color Doppler ultrasound evaluation.
• 6 Female subjects of childbearing age should agree to use contraceptive measures (such as intrauterine devices, contraceptives, or condoms) during the study period and within 6 months after the end of the study; serum pregnancy/urine within 7 days before study entry The pregnancy test is negative and must be a non-lactating subject; male subjects should agree that contraception must be used during the study period and within 6 months after the end of the study period.

Exclusion Criteria:

• 1 Combined diseases and medical history:

  1. Has had other malignant tumors within 3 years before the first medication. The following two conditions can be included in the group: other malignant tumors treated with a single operation to achieve disease-free survival (DFS) for 5 consecutive years; cured cervical carcinoma in situ, non-melanoma skin cancer and superficial bladder tumors [ Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor infiltrating basement membrane)];
  2. Unrelieved toxic reactions higher than Common Terminology Criteria Adverse Events (CTC AE) level 1 or higher caused by any previous treatment, excluding hair loss;
  3. Major surgical treatment, obvious traumatic injury or long-term unhealed wounds or fractures have been received within 28 days before the first medication;
  4. Arterial/venous thrombosis occurred within 6 months before the first administration, such as cerebrovascular accident (including temporary ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism;
  5. Existence of active pulmonary tuberculosis, history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonia, radiation pneumonia requiring treatment or active pneumonia with clinical symptoms;
  6. People who have a history of psychotropic drug abuse and cannot be quit or have mental disorders;
  7. Previous recipients of allogeneic bone marrow transplantation or solid organ transplantation.
  8. Subjects with any severe and / or uncontrolled disease.

• 2 Tumor-related symptoms and treatment:

  1. Have received chemotherapy, radiotherapy or other anti-cancer therapies within 4 weeks before the first medication (the washout period will be calculated from the end of the last treatment); if you have received local radiotherapy in the past, you can join the group if the following conditions are met: End of radiotherapy more than 4 weeks from the start of the study treatment (brain radiotherapy is more than 2 weeks); and the target lesion selected for this study is not in the radiotherapy area; or the target lesion is located in the radiotherapy area, but progress has been confirmed.
  2. Received Chinese patent medicine treatment with anti-tumor indications specified in the National Medical Products Administration (NMPA) approved drug instructions within 2 weeks before the first medication;
  3. Have previously received immunological double-antibody therapeutic drugs against the same target of TQB2868 injection;
  4. Uncontrollable pleural effusion, pericardial effusion or ascites that still needs to be drained repeatedly (investigator's judgment);
  5. Known to have spinal cord compression, cancerous meningitis, accompanied by brain metastasis symptoms, or symptom control time less than 2 weeks;

• 3 Research and treatment related:

  1. The history of live attenuated vaccine vaccination within 28 days before the first administration or the planned live attenuated vaccine vaccination during the research period;
  2. Those who have had severe hypersensitivity reactions after using macromolecular drugs;
  3. An active autoimmune disease that requires systemic treatment (such as the use of disease-relieving drugs, corticosteroids, or immunosuppressive agents) occurred within 2 years before the first medication. Alternative therapies (such as thyroxine, insulin, or physiological corticosteroids for adrenal or pituitary insufficiency, etc.) are not considered systemic treatments;
  4. Diagnosed with immunodeficiency or receiving systemic glucocorticoid therapy or any other form of immunosuppressive therapy (dose>10mg/day prednisone or other curative hormones), and continue within 2 weeks of the first administration in use;

• 4 Participated in other anti-tumor drug clinical trials within 4 weeks before the first medication;

• 5 According to the judgment of the researcher, there are situations that seriously endanger the safety of the subjects or affect the completion of the research by the subjects.