Clinical trial NCT04611711: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Patients With Digestive System Tumors Resistant to PD-1 Inhibitors
Lead sponsor: Peking University
Sponsor class: OTHER
First posted: 2020-11-02
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Overall response rate (ORR)
timeFrame: up to 48 weeks
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: up to 48 weeks
Other outcomes:
Locations:
Study officials:
References: