Trial Title:
TQB2450 Injection Combined With Chemotherapy Followed by Sequential Combination With Anlotinib Hydrochloride Capsule for First-line Treatment of Advanced Squamous Non-small Cell Lung Cancer.
NCT ID:
NCT05718167
Condition:
Advanced Squamous Non-Small Cell Lung Carcinoma
Conditions: Official terms:
Carcinoma, Non-Small-Cell Lung
Tislelizumab
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Not yet 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
Description:
TQB2450 is a humanized monoclonal antibody targeting the programmed death ligand 1
(PD-L1), which prevents PD-L1 from binding to the PD-1 and B7.1 receptors on the surface
of T cells, making T cells recover their activity, thereby enhancing the immune response.
Arm group label:
TQB2450 Injection and Anlotinib Hydrochloride Capsules
Intervention type:
Drug
Intervention name:
Anlotinib hydrochloride capsule
Description:
Anlotinib hydrochloride is a multi-target receptor tyrosine kinase inhibitor, which can
target angiogenesis related kinases, such as VEGFR 1/2/3, FGFR 1/2/3 and other tumor cell
proliferation related kinases like Platelet-derived growth factor receptor (PDGFR) α/β、
C-kit, RET.
Arm group label:
TQB2450 Injection and Anlotinib Hydrochloride Capsules
Intervention type:
Drug
Intervention name:
Tislelizumab injection
Description:
Tislelizumab injection can bind to human programmed cell death 1 (PD-1), a cell membrane
protein that is mainly expressed on activated T cells and inhibits T cell activation.
Arm group label:
Tislelizumab Injection
Summary:
This is Phase 3, randomized, double-blind, parallel controlled study designed to evaluate
the Progression Free Survive (PFS) of TQB2450 injection combined with Paclitaxel
Injection and Carboplatin Injection Followed by TQB2450 injection combined with Anlotinib
Hydrochloride Capsules versus Tislelizumab injection combined with Paclitaxel Injection
and Carboplatin Injection followed by Tislelizumab injection in locally advanced (stage
ⅢB/ⅢC) and metastatic or recurrent (Stage IV) squamous NSCLC subjects.The primary
endpoint is PFS assessed by IRC.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- According to the 8th edition of the International Association for the Study of Lung
Cancer and the American Joint Committee on Cancer Classification, the Tumour, node
and metastasis (TNM) staging of lung cancer is locally advanced (stage ⅢB/ⅢC),
metastatic or recurrent ( Stage IV) NSCLC patients.
- Between the ages of 18-75 years (calculated based on the date of signing ICF); male
or female; Eastern cooperative oncology group (ECOG) score 0-1; estimated survival
time ≥ 3 months.
- According to the RECIST 1.1 standard, there is at least one measurable lesion. If
the measurable lesion is located in the radiotherapy area, it should be clearly
defined as a progressive state.
- Patients who have not received systemic anti-tumor therapy for advanced, recurrent
or metastatic diseases in the past. For those who have received adjuvant
chemotherapy in the past, the interval between the recurrence time and the last
adjuvant chemotherapy should be at least 6 months; The interval between the end of
previous radiotherapy for chest and this treatment should be more than 6 months, and
the interval between palliative radiotherapy for chest and this treatment should be
more than 7 days.
- Tumor tissue sections that have not undergone radiotherapy at or after the diagnosis
of advanced or metastatic NSCLC must be provided.These are Used for PD-L1 expression
detection.Tumor tissue samples must be archived samples or freshly obtained samples
within 12 months before randomization.
- main organ function is good, meet the following standards.
1. Routine blood examination standards (without blood transfusion or correction
with hematopoietic stimulating factor drugs within 14 days before screening):
1. Absolute neutrophil count (ANC) ≥1.5×109 /L;
2. Platelets ≥100×109 /L;
3. Hemoglobin ≥90 g/L.
2. The blood biochemical examination shall meet the following standards:
1. Total bilirubin (TBIL) ≤ 2 × upper limit of normal (ULN) (Patients with
Gilbert syndrome ≤ 3 × ULN);
2. Alanine aminotransferase (ALT) and aspartate aminotransferase
(AST)≤2.5×ULN. If it is accompanied by liver metastasis, ALT and
AST≤5×ULN;
3. Serum creatinine (Cr) ≤1.5×ULN or creatinine clearance estimated by
Cockcroft-Gault glomerular filtration formula ≥60 mL/min;
4. Serum albumin (ALB) ≥30g/L.
3. Urine routine examination standard: urine routine indicates urine protein <++;
if urine protein ≥++, it is necessary to confirm that the 24-hour urine protein
quantitative ≤1.0 g.
4. Blood coagulation test standards: prothrombin time (PT), activated partial
thromboplastin time (APTT), international normalized ratio (INR)≤1.5×ULN (no
anticoagulant therapy).
5. Thyroid Stimulating Hormone (TSH) ≤ ULN; if abnormal, T3 and T4 levels should
be examined. If T3 and T4 levels are normal, it can be selected.
6. Heart color Doppler ultrasound assessment: Left ventricular ejection fraction
(LVEF) ≥50%.
7. 12-lead ECG evaluation: QTc<450ms (male), QTc<470ms (female).
- Women of childbearing age should agree to use effective contraceptive measures
during the study period and 6 months after the end of the study, and have a negative
serum pregnancy test within 7 days before the study enrollment; men should agree to
the study period and 6 months after the end of the study period Effective
contraceptive measures must be used internally.
- The subjects voluntarily joined the study, signed the informed consent form, and had
good compliance.
Exclusion Criteria:
- Tumor disease and medical history:
1. Brain metastasis exists before enrollment. Subjects meeting one of the
following requirements can be included;
1. Have received brain metastasis treatment (surgery/radiotherapy) in the
past and meet all the following criteria:
- only supratentorial metastasis and cerebellar metastasis,
- the condition needs to be stable for ≥ 2 weeks and no imaging
evidence of new brain metastasis or brain metastasis expansion is
found;
- there is no brain metastasis symptom, and the subject must have
stopped using corticosteroids/dehydrators for at least 2 weeks before
starting to use the trial drug;
2. The patient has not received brain metastasis treatment in the past and
meets all the following criteria:
- the maximum diameter of the lesion is less than 2cm;
- the condition needs to be stable for ≥ 2 weeks (no imaging evidence
of new brain metastasis or expanded brain metastasis is found), and
there is no neurological symptoms caused by brain tissue compression;
- the subject must have stopped using corticosteroids/dehydrating
agents for at least 2 weeks before starting to use the test drug;
2. There are midbrain, pons, medulla oblongata, spinal cord and meningeal
metastases；
3. Other malignant tumors appeared or were present within 3 years. The following
two cases can be included: other malignant tumors treated by single operation
have achieved 5-year Disease-free survival (DFS) in a row; The cured cervical
carcinoma in situ, non melanoma skin cancer and superficial bladder tumor [ta
(non-invasive tumor), tis (carcinoma in situ) and T1 (tumor infiltrating
basement membrane)];
4. Central type, cavity squamous cell carcinoma (primarily in the main bronchus
and around the hilar);Imaging shows that the tumor invades large blood vessels
or is unclearly separated from the blood vessels, or the investigator judges
that the tumor is likely to invade important blood vessels and cause fatal
bleeding during the subsequent study(The major vessels in the chest include
pulmonary aorta, left pulmonary artery, right pulmonary artery, four pulmonary
veins, superior vena cava, inferior vena cava and aorta);
5. There is spinal cord compression and/or severe bone injury caused by tumor bone
metastasis, including pathological fracture and severe bone pain with poor
control;
6. Patients with serous cavity (thoracic cavity, abdominal cavity, or pericardial
cavity) that require repeated drainage to relieve clinical symptoms (as
determined by the investigator), or who have received drainage of serous cavity
effusion for the purpose of treatment within 2 weeks before treatment.
- Previous anti-tumor treatments:
1. Received the treatment of proprietary Chinese medicines with anti-tumor
indications specified in the China National Medical Products Administration
(NMPA) approved drug instructions within 2 weeks before the start of the study
treatment(Including compound cantharidin capsules, Kangai injection, Kanglaite
capsule/injection, Aidi injection, brucea javanica oil injection/capsule,
Xiaoaiping tablet/injection, Huachansu capsule, etc.);
2. Previously received related immunotherapy drugs for programmed death 1 (PD-1),
PD-L1, cytolytic T lymphocyte-associated antigen-4 (CTLA-4), etc.;
3. Previous use of anti-angiogenic drugs such as bevacizumab, anlotinib, apatinib,
lenvatinib, sorafenib, sunitinib, regorafenib, fruquintinib, etc.;
4. Failure to recover from the toxicity and/or complications of previous
interventions to CTCAE ≤1, except for hair loss and peripheral neuropathy ≤2;
- Combined diseases and medical history:
1. Liver cirrhosis, active hepatitis*;(Note: active hepatitis (hepatitis B
reference: HBV-DNA > 1*103 copy /mL or > 2000IU/mL) when HBsAg is positive.
Hepatitis C reference: Hepatitis C virus (HCV) antibody is positive, and HCV
titer detection value exceeds the upper limit of normal value);
2. Renal abnormalities: i.Renal failure requires hemodialysis or peritoneal
dialysis; ii.Previous or existing nephrotic syndrome, chronic nephritis.
3. Cardiovascular and cerebrovascular abnormalities：
1. Patients with previous or present heart failure, degree II or above heart
block:
2. Myocardial infarction or unstable angina, supraventricular or ventricular
arrhythmia with clinical significance need treatment or intervention;
3. Vascular embolism and cerebrovascular accident (including transient
ischemic attack, cerebral hemorrhage and cerebral infarction) occurred
within 9 months（ Prophylactic use of anticoagulant therapy is allowed for
patients with thrombotic tendency or undergoing anticoagulant therapy.)
4. After more than two kinds of drug treatment, blood pressure control is
still not ideal (systolic blood pressure ≥ 150 mmHg or diastolic blood
pressure ≥ 90 mmHg).
4. Gastrointestinal abnormalities:
1. Inability to take medications (such as inability to swallow, intestinal
obstruction, etc.);
2. A history of malabsorption syndrome or other diseases that interfere with
gastrointestinal absorption;
3. Received treatment for active peptic ulcer in the past 6 months;
4. Despite the maximum medical treatment, chronic diarrhea of grade 2 and
above continues to occur;
5. Other conditions determined by the researcher that may cause
gastrointestinal bleeding and perforation.
5. History of immunodeficiency:
1. Have a history of immunodeficiency, including HIV positive or other
acquired or congenital immunodeficiency diseases;
2. Active autoimmune disease or history of autoimmune disease, including but
not limited to Crohn's disease, ulcerative colitis, autoimmune
hepatitis/enteritis/vasculitis/nephritis, etc.
3. Prepare to undergo or have previously received an organ transplant;
4. Patients who require systemic or topical immunosuppressive therapy to
achieve immunosuppressive purposes and need to continue to use them within
two weeks before randomization (except for glucocorticoid daily dose <10
mg prednisone or other equivalent hormones). (Note: Hormone replacement
therapy (such as thyroxine, insulin, or physiological corticosteroid
replacement therapy for adrenal or pituitary insufficiency, etc.) is not
considered as systemic therapy and allowed to be used.)
6. Bleeding risk:
1. Suffered from bleeding or coagulopathy within 28 days before the start of
treatment or was using warfarin, aspirin and other antiplatelet
agglutination drugs (except for aspirin ≤100 mg/d preventive drugs);
2. Had hemoptysis >2.5 mL/day in 28 days before the start of treatment;
3. Regardless of the severity, patients with any history of bleeding or
coagulopathy;
4. Received major surgical treatment, open biopsy, etc. within 28 days before
the start of the study treatment;
5. Long-term unhealed wounds or fractures, except for pathological fractures;
7. Poor control of type I diabetes or II diabetes (fasting blood glucose (FBG)>
10mmol/L);
8. Severe infections within 4 weeks before the start of study treatment, including
but not limited to hospitalization due to bacteremia, severe pneumonia, or
other severe infections; subjects with ≥ grade 2 active infections within 4
weeks before the start of study treatment Or fever of unknown cause occurred
during the screening period and before the first administration>38.0℃;
9. Past or existing pneumoconiosis, interstitial pneumonia, (non-infectious)
pneumonia that requires adrenal corticosteroid therapy, currently suffering
from other types of pneumonia ≥2, or lung function tests confirmed severely
impaired lung function (Forced Expiratory Volume in the first second (FEV1) or
diffusing capacity of lung for carbon monoxide(DLCO) or DLCO per alveolar
volume (DLCO /VA) accounts for the expected value %<40%) and other objective
evidence;
10. Patients with active tuberculosis within 1 year before enrollment; subjects
with a history of active pulmonary tuberculosis infection 1 year ago must
provide clear evidence of cure before enrollment; if tuberculosis is suspected
during the screening period, chest radiographs and sputum must be passed Enter
the group only after the liquid and clinical symptoms are eliminated;
11. Allergies, or a history of severe allergies in the past, or severe
hypersensitivity reactions after receiving other monoclonal antibody
treatments, or known allergies to the ingredients of the study drug excipients;
12. Previous history of severe mental disorders;
13. People with a history of drug abuse, alcohol or drug abuse;
- The end of the previous clinical study (last dose) is less than 4 weeks or the study
drug's 5 half-lives, whichever is shorter.
- Live attenuated vaccine vaccination history within 28 days before randomization or
planned live attenuated vaccination during the study period. Seasonal influenza
vaccine for injection is usually an inactivated virus vaccine and is allowed to be
vaccinated during the study period.
- Female patients during pregnancy or lactation.
- For patients with known epidermal growth factor receptor (EGFR) sensitive mutation,
anaplastic lymphoma kinase (ALK) fusion and ROS proto-oncogene 1 (ROS1) fusion,
detection is not mandatory for those with unknown gene status
- According to the investigator's point of view, it may increase the risks associated
with participating in the study, or other severe, acute or chronic medical diseases
or laboratory abnormalities that may interfere with the interpretation of the study
results, or other reasons that are not suitable for participating in this clinical
study.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Chinese Academy of Medical Sciences Cancer Hospital
Address:
City:
Beijing
Zip:
100021
Country:
China
Contact:
Last name:
Yuankai Shi, Doctor
Phone:
+86 13701251865
Email:
syuankaipumc@126.com
Facility:
Name:
Beijing Chest Hospital, Capital Medical University
Address:
City:
Beijing
Zip:
101149
Country:
China
Contact:
Last name:
Tongmei Zhang, Doctor
Phone:
+86 13683016715
Email:
tongmeibj@163.com
Facility:
Name:
TianJin Medical University Cancer Institute & Hospital
Address:
City:
Tianjin
Zip:
300060
Country:
China
Contact:
Last name:
DingZhi Huang, Doctor
Phone:
+86 18622221232
Email:
dingzhi72@163.com
Facility:
Name:
Yunnan Cancer Hospital
Address:
City:
Kunming
Zip:
650118
Country:
China
Contact:
Last name:
RunXiang Yang, Doctor
Phone:
+86 13888876721
Email:
13888876721@163.com
Start date:
February 2023
Completion date:
October 2025
Lead sponsor:
Agency:
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Agency class:
Industry
Source:
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05718167
