Trial Title:
Phase II Clinical Trial to Evaluate the Safety and Efficacy of TQB2450 Injection Combined With Anlotinib Capsule and Chemotherapy in the Treatment of Immunoresistant Advanced Non-small Cell Lung Cancer
NCT ID:
NCT06141226
Condition:
Non-small-cell Lung Cancer
Conditions: Official terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Docetaxel
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Intervention:
Intervention type:
Drug
Intervention name:
TQB2450 +Anlotinib+Docetaxel
Description:
TQB2450 is a humanized monoclonal antibody targeting programmed death ligand 1 (PD-L1),
which prevents PD-L1 from binding to PD-1 and B7.1 receptors on the surface of T cells,
restoring T cell activity and enhancing immune response. It has the potential to treat
various types of tumors.
Anlotinib is a multi target receptor tyrosine kinase (RTK) inhibitor. It can inhibit
VEGFR1, VEGFR2, VEGFR3, c-Kit, PDGFR β Activity.
Docetaxel is a taxane based anti-tumor drug.
Arm group label:
TQB2450 +Anlotinib+Docetaxel
Other name:
TQB2450/Anlotinib/Docetaxel
Intervention type:
Drug
Intervention name:
TQB2450 +Androtinib Placebo+Docetaxel
Description:
TQB2450 is a humanized monoclonal antibody targeting programmed death ligand 1 (PD-L1),
which prevents PD-L1 from binding to PD-1 and B7.1 receptors on the surface of T cells,
restoring T cell activity and enhancing immune response. It has the potential to treat
various types of tumors.
Androtinib Placebo Docetaxel is a taxane based anti-tumor drug.
Arm group label:
TQB2450 +Androtinib Placebo+Docetaxel
Other name:
TQB2450/Anlotinib Placebo/Docetaxel
Summary:
Objective to compare the efficacy and safety of TQB2450 injection combined with anlotinib
and chemotherapy, and TQB2450 injection combined with chemotherapy in the treatment of
advanced non-small cell lung cancer subjects who failed to receive first-line
chemotherapy combined with immunization, and to explore and evaluate biomarkers related
to efficacy, mechanism of action / resistance mechanism, and safety.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. According to the International Association for the Study of Lung Cancer and the
Joint Committee on the American Classification of Cancer, 8th edition TNM staging of
lung cancer, patients with locally advanced (stage IIIB/IIIC), metastatic or
recurrent (stage IV) NSCLC who are histologically proven to be inoperable and unable
to undergo radical synchronous radiotherapy and chemotherapy.
2. 18 years old ≤ age ≤ 75 years old; No gender limit; ECOG score 0-1 points; The
expected survival period is ≥ 3 months.
3. According to RECIST 1.1 standard, there should be at least one measurable lesion.
4. Tumor resistance has progressed after receiving first-line treatment with immune
checkpoint inhibitors (including PD-1 or PD-L1 monoclonal or dual antibodies)
combined with platinum based drugs in the past. For neoadjuvant/adjuvant
chemotherapy or radiotherapy or concurrent radiotherapy and chemotherapy, if the
disease progresses during treatment or within 6 months after discontinuation of
treatment, it should be considered as a first-line treatment plan.
5. It is necessary to provide tumor tissue sections that have been diagnosed with
advanced or metastatic NSCLC and have not undergone radiotherapy (at least 5 samples
are required for PD-L1 testing of tumor tissue, but if testing has been conducted
before the first line treatment, recognized test results from each participating
center can be accepted.) Tumor tissue samples must be archived samples or freshly
obtained samples within the first 12 months of randomization.
6. Except for patients with squamous NSCLC, enrolled patients need to demonstrate the
absence of EGFR gene sensitive mutations, ALK fusion oncogenes, or ROS1 fusion
oncogenes. If it is adenosquamous cell carcinoma, stratification needs to be
determined based on the dominant tissue composition.
7. Good function of main organs
8. Women of childbearing age should agree to use effective contraceptive measures
during the study period and within 6 months after the end of the study. Serum
pregnancy or urine pregnancy tests should be negative within 7 days before
enrollment in the study; Men should agree to use effective contraceptive measures
during the study period and within 6 months after the end of the study period.
9. The subjects voluntarily joined this study, signed an informed consent form, and had
good compliance.
Exclusion Criteria:
1. Tumor diseases and medical history:
a) If there is a central nervous system metastasis before enrollment,
enrollment can be made if all the following criteria are met: i. Previously
received brain metastasis treatment and met all of the following criteria:
① Only supratentorial and cerebellar metastases are allowed (i.e. transfer to
the midbrain, pons, medulla, or spinal cord is not allowed);
② No imaging evidence of new or enlarged brain metastases was found;
③ There are no symptoms of brain metastasis, and the subject must have stopped
using corticosteroids/dehydrating agents for at least 2 weeks before starting
to use the investigational drug.
Ii. Has not received brain metastasis treatment in the past and meets all of
the following criteria:
- No more than 3 metastatic lesions; ② The total length and diameter of all
lesions ≤ 1.5cm;
- There are no neurological symptoms caused by brain tissue
compression;
④ Before starting to use the investigational drug, the subject must
have stopped using corticosteroids/dehydrating agents for at least 2
weeks.
b) There were no active malignant tumors for ≤ 2 years before
randomization. c) Central type squamous cell carcinoma with a cavity
(primary in the main bronchus and around the hilum of the lungs).
d) Imaging shows that the tumor invades large blood vessels, or the
boundary between the tumor and the blood vessels is unclear, or the
researcher determines that the tumor is highly likely to invade
important blood vessels and cause fatal massive bleeding during
subsequent studies.
e) (1) Severe bone damage caused by tumor bone metastasis, including
pathological fractures of load-bearing bones (such as spinal
vertebrae, pelvis, femur, tibia, phalanges, calcaneus, etc.) and
spinal cord compression that occur within 6 months; (2) Imaging
examination suggests the presence of three or more multiple bone
metastases in the load-bearing bone.
f) Patients with serous cavity (pleural, abdominal, or pericardial)
effusion that requires repeated drainage to alleviate clinical
symptoms (as determined by the researcher), or those who have
received serous cavity effusion drainage for treatment purposes
within 2 weeks prior to treatment.
2. Previous anti-tumor treatment:
1. Within 2 weeks before the start of the study treatment, he received
traditional Chinese patent medicines and simple preparations with
anti-tumor indications specified in the NMPA approved drug instructions.
2. I have previously used anti angiogenic drug systems such as arotinib,
apatinib, lenvatinib, sorafenib, sunitinib, regofinib, and furoquitinib to
treat locally advanced or metastatic NSCLC.
3. Previously received docetaxel for systematic treatment of locally advanced
or metastatic NSCLC.
4. Unacceptable toxicity after previous anti PD - (L) 1 treatment.
5. Patients who have received medication with immunomodulatory effects within
30 days before starting treatment.
6. Before randomization, there are any symptoms that require systemic
treatment with corticosteroids (prednisone or equivalent doses of similar
drugs above 10 mg/d) or other immunosuppressive agents for ≤ 14 days.
7. Failure to recover from toxicity and/or complications of previous
intervention measures to CTCAE ≤ 1 level, except for peripheral neuropathy
with hair loss and ≤ 2 level.
3. Concomitant diseases and medical history:
a) Decompensated cirrhosis (Child Pugh liver function rating B or C), active
hepatitis, and active COVID-19 infection.
b) Renal abnormalities: i. Renal failure requires hemodialysis or peritoneal
dialysis; Ii. Previous or existing nephrotic syndrome (excluding cured),
chronic nephritis.
c) Cardiovascular and cerebrovascular abnormalities: d) Gastrointestinal
abnormalities: i. Inability to take medication orally; Ii. History of
malabsorption syndrome or other diseases that can interfere with
gastrointestinal absorption, including a history of partial surgical removal of
the stomach or intestines (excluding appendectomy); Iii. Received treatment for
active gastrointestinal ulcers within the past 6 months.
e) History of Immunodeficiency: i. Having a history of immunodeficiency,
including HIV positive or suffering from other acquired or congenital
immunodeficiency diseases; Ii. A history of active autoimmune diseases or
autoimmune diseases, including but not limited to Crohn's disease, ulcerative
colitis, autoimmune hepatitis/enteritis/vasculitis/nephritis, etc; Iii. Prepare
to undergo or have previously received organ transplantation; f) Bleeding risk:
i. Suffering from bleeding, coagulation disorders, or using warfarin, aspirin,
and other antiplatelet agglutination drugs within 28 days prior to the start of
treatment (excluding preventive medication with aspirin ≤ 100 mg/d); Ii. Have a
history of hemoptysis within 28 days before the start of treatment; Iii.
Regardless of the severity, patients with congenital bleeding or coagulation
disorders, or those who are currently using anticoagulants for treatment; Iv.
Major surgical treatment or obvious traumatic injury received within 28 days
prior to the start of the study treatment; v. Long term uncured wounds or
fractures, excluding pathological fractures. g) Type I diabetes or II diabetes
is poorly controlled. h) Having experienced severe infection of level 4 or
higher within one year prior to the start of the study treatment; Subjects with
2-3 levels of active infection within 2 weeks prior to the start of study
treatment; Treponema pallidum antibody (TP Ab) positive; Or those who
experience unexplained fever of>38.0 ℃ during the screening period or before
the first administration, or who require medical intervention.
i) Previous or existing pneumoconiosis, interstitial pneumonia, non infectious
pneumonia requiring corticosteroid treatment, currently suffering from grade 2
or other types of pneumonia, or objective evidence of severe impairment of lung
function confirmed by pulmonary function examination (FEV1 or DLCO or DLCO/VA
accounting for% of expected value<40%).
j) Patients with active tuberculosis within one year prior to enrollment. k)
Allergic constitution, or a history of severe allergies, or severe
hypersensitivity reactions after receiving other monoclonal antibody
treatments, or known allergies to the study drug excipients, or allergies to
Tween 80.
l) Previous history of severe mental disorders. m) Individuals with a history
of drug abuse, alcohol or drug abuse.
4. The end of previous clinical studies (last administration) is less than 4 weeks
or the 5 half-lives of the study drug, whichever is shorter.
5. Vaccination history within the first 28 days of randomization or vaccination
during the planned study period.
6. Pregnant or lactating female patients.
7. According to the researcher's viewpoint, it may increase the risk associated
with participating in the study, or other reasons may make it unsuitable to
participate in this clinical study.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
The Central People's Hospital of Huizhou
Address:
City:
Huizhou
Zip:
516001
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Hailin Xiong, Doctor
Phone:
15976198371
Email:
Jndx23207@126.com
Facility:
Name:
The First Affiliated Hospital of Nanyang Medical College
Address:
City:
Nanyang
Zip:
473000
Country:
China
Status:
Recruiting
Contact:
Last name:
Peng Cheng, Master
Phone:
13782042723
Email:
oncologist@163.com
Facility:
Name:
The Second People's Hospital of Lianyungang
Address:
City:
Lianyungang
Zip:
222000
Country:
China
Status:
Recruiting
Contact:
Last name:
Cheng Chen, doctor
Phone:
15261349056
Email:
chenchenggood@163.com
Facility:
Name:
Weihai Municipal Hospital
Address:
City:
Weihai
Zip:
264299
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Fujun Yang, Doctor
Phone:
13181149906
Email:
58500775@qq.com
Facility:
Name:
Tianjin Medical University Cancer Institute and Hospital
Address:
City:
Tianjin
Zip:
300060
Country:
China
Status:
Recruiting
Contact:
Last name:
Kai Li, doctor
Phone:
18622221218
Email:
likai@tjmuch.com
Contact backup:
Last name:
Jing Wang, doctor
Phone:
18622228650
Email:
wangjing_0220@163.com
Start date:
April 12, 2023
Completion date:
December 30, 2028
Lead sponsor:
Agency:
Tianjin Medical University Cancer Institute and Hospital
Agency class:
Other
Source:
Tianjin Medical University Cancer Institute and Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06141226
