Patients With Digestive System Tumors Resistant to PD-1 Inhibitors
Conditions
Brief summary
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.
Interventions
DRUGdecitabine＋ TQB2450 injection
Real low-dose epigenetics drugs (decitabine) can reverse the resistance of PD-1 inhibitors by re-regulating the immune microenvironment. TQB2450 is a humanized monoclonal antibody targeting PD-L1, which prevents PD-L1 from binding to the PD-1 and B7.1 receptors on the surface of T cells, so as to restore the activity of T cells and thereby enhance the immune response, and has the potential to treat various types of tumors.
DRUGdecitabine＋ TQB2450 injection＋Anlotinib
Real low-dose epigenetics drugs (decitabine) can reverse the resistance of PD-1 inhibitors by re-regulating the immune microenvironment. TQB2450 is a humanized monoclonal antibody targeting PD-L1, which prevents PD-L1 from binding to the PD-1 and B7.1 receptors on the surface of T cells, so as to restore the activity of T cells and thereby enhance the immune response, and has the potential to treat various types of tumors. Anlotinib Hydrochloride is a multi-target receptor tyrosine kinase inhibitor with significant inhibitory activity against angiogenesis related kinases (VEGFR1/2/3, FGFR1/2/3, etc.) and other tumor cell proliferation-related kinases (PDGFR /, C-Kit, RET, etc.), which can play a dual role in anti-tumor angiogenesis and tumor growth inhibition.
Sponsors
Peking University
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall response rate (ORR) | up to 48 weeks | Objective response rate refers to the percentage of complete (CR) or partial response (PR) subjects determined by the investigator based on RECIST 1.1 or iRECIST (CR under iRECIST criteria, PR can occur after imaging disease progression). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival (OS) | up to 48 weeks | Overall survival defined as the time from enrollment to death from any cause. |
Contacts
Primary ContactLin Shen
Outcome results
None listed