Back to resultsPhase 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
Primary Purpose
Patients With Digestive System Tumors Resistant to PD-1 Inhibitors
Status
Unknown status
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
decitabine＋ TQB2450 injection
decitabine＋ TQB2450 injection＋Anlotinib
Sponsored by
About this trial
This is an interventional treatment trial for Patients With Digestive System Tumors Resistant to PD-1 Inhibitors
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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Other
Other
Arm Label
decitabine＋ TQB2450 injection (PD-L1 monoclonal antibody)
decitabine + anlotinib ＋ TQB2450 injection (PD-L1 monoclonal antibody)
Arm Description
Decitabine (10mg ivgttqd, d1-5) combined with TQB2450 injection (1200mg ivgtt, d5)
Decitabine and Anlotinib (decitabine 10mg ivgtt qd, d1-5; Anlotinib 8mg po.qd, d5-18) combined with TQB2450 injection (1200mg ivgtt, d5), using the traditional 3+3 experimental design (First enroll 3 subjects. If 1 case of DLT is observed, 3 more subjects need to be added to the same dose group to further evaluate the toxicity) to observe DLT to evaluate MTD. The trial starts from the 8mg dose of Anlotinib Start.
Outcomes
Primary Outcome Measures
Overall response rate (ORR)
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 Outcome Measures
Overall survival (OS)
Overall survival defined as the time from enrollment to death from any cause.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04611711
Brief Title
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
2. Study Status
Record Verification Date
September 2020
Overall Recruitment Status
Unknown status
Study Start Date
November 1, 2020 (Anticipated)
Primary Completion Date
December 1, 2020 (Anticipated)
Study Completion Date
December 1, 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Peking University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Patients With Digestive System Tumors Resistant to PD-1 Inhibitors
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
60 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
decitabine＋ TQB2450 injection (PD-L1 monoclonal antibody)
Arm Type
Other
Arm Description
Decitabine (10mg ivgttqd, d1-5) combined with TQB2450 injection (1200mg ivgtt, d5)
Arm Title
decitabine + anlotinib ＋ TQB2450 injection (PD-L1 monoclonal antibody)
Arm Type
Other
Arm Description
Decitabine and Anlotinib (decitabine 10mg ivgtt qd, d1-5; Anlotinib 8mg po.qd, d5-18) combined with TQB2450 injection (1200mg ivgtt, d5), using the traditional 3+3 experimental design (First enroll 3 subjects. If 1 case of DLT is observed, 3 more subjects need to be added to the same dose group to further evaluate the toxicity) to observe DLT to evaluate MTD. The trial starts from the 8mg dose of Anlotinib Start.
Intervention Type
Drug
Intervention Name(s)
decitabine＋ TQB2450 injection
Intervention Description
"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."
Intervention Type
Drug
Intervention Name(s)
decitabine＋ TQB2450 injection＋Anlotinib
Intervention Description
"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. "
Primary Outcome Measure Information:
Title
Overall response rate (ORR)
Description
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).
Time Frame
up to 48 weeks
Secondary Outcome Measure Information:
Title
Overall survival (OS)
Description
Overall survival defined as the time from enrollment to death from any cause.
Time Frame
up to 48 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Lin Shen
Phone
86-10-88196561
Email
shenlin@bjmu.edu.cn
12. IPD Sharing Statement
Learn more about this trial
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
We'll reach out to this number within 24 hrs