Phase I/II Clinical Study of Decitabine Combined With TQB2450 Injection or Decitabine + Anlotinib Combined With TQB2450 Injection in the Treatment of PD-1 Monoclonal Antibody-resistant Digestive System Tumors

An Evaluation of the Effectiveness and Safety of Decitabine Combined With TQB2450 Injection (PD-L1 Monoclonal Antibody) or Decitabine + Anlotinib Combined With TQB2450 Injection in the Treatment of PD-1 Monoclonal Antibody-resistant Digestive System Tumors I /Phase II Clinical Study

This clinical study focused on patients with digestive system tumors resistant to PD-1 inhibitors, and explored the reversal resistance of epigenetic drugs (decitabine) and TKI drugs (anlotinib) in this part of patients.

Inclusion Criteria:

• Voluntary participation and written informed consent;
• Age: 18-70 years old;
• No gender limitation;
• Digestive system malignant tumor diagnosed by pathology;
• Previously received PD-1 monoclonal antibody Or the combination therapy fails;
• There is at least one measurable lesion (according to the RECIST1.1 standard) or an unmeasurable lesion that can be evaluated, and the imaging diagnosis is ≤21 days from the selection time；
• The expected survival period is ≥3 months;
• General physical status (ECOG) 0-1;
• Sufficient bone marrow hematopoietic function (within 7 days); normal liver and kidney function (within 14 days)；
• Heart, lung, kidney, and liver functions are generally normal.

Exclusion Criteria:

• People who are currently receiving other effective treatments;
• Patients who have been treated with anti-vascular TKI drugs in the past;
• Patients who have participated in other clinical trials within 4 weeks before enrollment;
• Allergic to study drugs;
• Those without measurable tumor lesions, such as body cavity effusion or diffuse infiltration of organs;
• Those with measurable lesions that have received radiotherapy.
• Patients with other primary malignant tumors other than digestive system tumors at the same time, except for early solid tumors that have been cured for more than 1 year;
• Clinically significant cardiovascular diseases, such as heart failure (NYHAIII-IV), are not controlled A history of coronary heart disease, cardiomyopathy, arrhythmia, uncontrolled hypertension or myocardial infarction within the past 1 year;
• Neurological or mental disorders that affect cognitive ability, including central nervous system metastasis;
• Existed within 14 days before enrollment Active severe clinical infections (>grade 2 NCI-CTCAE version 5.0), including active tuberculosis;
• Known or self-reported HIV infection or active hepatitis B or C;
• Uncontrolled Systemic diseases, such as poorly controlled diabetes;
• A history of interstitial lung disease, such as interstitial pneumonia, pulmonary fibrosis, or evidence of interstitial lung disease on baseline chest X-ray/CT;
• Keratitis , Ulcerative keratitis or severe dry eye;
• Known hypersensitivity or allergic reaction to any component of the study drug;
• Pregnancy (determined by serum β-chorionic gonadotropin test) or breast-feeding.