| Eligibility |
Inclusion Criteria:
- The patient voluntarily joined the study, signed an informed consent form, had good
compliance, and cooperated with the follow-up.
- Unresectable locally advanced, unresectable recurrent or metastatic ESCC confirmed by
histopathology (excluding mixed adenosquamous carcinoma);
- Patients who have not received systemic treatment in the past, or who have previously
received (neo) adjuvant treatment/radical treatment programs (including radical
surgical resection and radical radiotherapy and chemotherapy programs) who have
relapsed for more than 6 months; Note: Including patients with advanced or recurring
non-target lesions who have progressed again after simple radiotherapy. For local
lesions (non-target lesions), the time from the end of palliative treatment to the
enrollment time is> 2 weeks;
- According to the RECIST version 1.1 of the curative effect evaluation standard for
solid tumors, there is at least one measurable lesion, and it can be accurately
measured by magnetic resonance imaging (MRI) or computed tomography (CT) in at least
one direction (the largest diameter needs to be recorded) , Where the longest diameter
at baseline is =10 mm (if it is a lymph node, the short diameter is required to be =15
mm); the measurable lesions should not have received local treatment such as
radiotherapy (the lesions located in the previous radiotherapy area, if it is
confirmed to have progressed, and meet RECIST1.1 standard, target lesions can also be
selected);
- Male or female patients between 18-75 years old;
- Eastern Cooperative Oncology Group (ECOG) physical status (PS) score: 0-1 points;
- The estimated survival period exceeds 3 months;
- Possess sufficient organ and bone marrow function, that is, meet the following
standards:
1. Routine blood examination standards must be met (no blood transfusion and blood
products within 14 days, no correction with G-CSF and other hematopoietic
stimulating factors):Hemoglobin content (HB) =100g/L; White blood cell content
(WBC) =3.0×10^9/L; Neutrophil count (ANC)=1.5×10^9/L; Platelet count (PLT)
=75×10^9/L.
2. The biochemical inspection shall meet the following standards:Total serum
bilirubin (TBIL) =1.5 times the upper limit of normal (ULN); ALT and AST=2.5ULN;
if there is liver metastasis, ALT and AST=5ULN;Cr=1.5ULN or creatinine clearance
rate (CCr)=60ml/min, (Cockcroft-Gault formula).
3. Adequate coagulation function, defined as International Normalized Ratio (INR) or
Prothrombin Time (PT) = 1.5 times ULN;
4. Doppler ultrasound evaluation: left ventricular ejection fraction (LVEF) = lower
limit of normal value (50%);
5. Myocardial enzyme spectrum: within the normal range.
- Women of childbearing age must take appropriate contraceptive measures from screening
to 3 months after stopping the study treatment, and participants must be non-lactating
patients. Before starting the administration, the pregnancy test is negative, or
meeting one of the following criteria proves that there is no risk of pregnancy:
1. Postmenopausal is defined as amenorrhea at least 12 months after the age is over
50 years and all exogenous hormone replacement therapy is stopped;
2. For women younger than 50 years old, if the amenorrhea is 12 months or more after
stopping all exogenous hormone treatments, and the luteinizing hormone (LH) and
follicle stimulating hormone (FSH) levels are within the laboratory
postmenopausal reference value range, also Can be considered post-menopausal;
3. Have received irreversible sterilization, including hysterectomy, bilateral
ovariectomy or bilateral fallopian tube resection, except for bilateral tubal
ligation.
- For men, participants must agree to use appropriate methods of contraception or have
been surgically sterilized during the trial period and 8 weeks after the last trial
drug administration;
Exclusion Criteria:
- Patients who have previously received Anlotinib hydrochloride treatment or any
anti-PD-1, anti-PD-L1, and anti-CTLA-4 antibody treatment;
- It is known that ESCC tends to be completely obstructed under endoscopy and requires
interventional therapy to relieve the obstruction;
- ESCC patients with ulcer; Note: This mainly refers to patients whose ulcers are
adjacent to blood vessels which increase the risk of bleeding.
- Patients who have received stent implantation in the esophagus or trachea;
- Patients who have a higher risk of bleeding or perforation due to the tumor's obvious
invasion of the adjacent organs (aorta or trachea) of the esophageal lesion, or
patients who have formed a fistula;
- Received major surgical treatment, open biopsy or obvious traumatic injury within 28
days before enrollment;
- There are a variety of factors that affect the use of therapeutic drugs, such as:
inability to swallow or chronic diarrhea or intestinal obstruction, significantly
affecting the administration and absorption of the drug, or a known history of severe
allergies to any of the drug components in this study.
- The patient has received anti-tumor treatment with Chinese medicine in the past 2
weeks (Chinese medicine contains the following medicinal materials such as Brucea
javanica, coix seed, lentinan, cantharidin, toad skin, astragalus, sophora flavescens,
black bone vine, myrobalan, etc.), However, patients who took more than 2 weeks from
the last anti-tumor treatment of Chinese medicine are allowed to join the group;
- The burden of liver metastases accounts for more than 50% of the entire liver volume;
- Patients with any severe and/uncontrolled diseases, including:
1. Patients with poor blood pressure control using antihypertensive drugs (systolic
blood pressure =150 mmHg or diastolic blood pressure =100 mmHg); or patients
using two or more antihypertensive drugs to control blood pressure; previous
hypertensive crisis or high Patients with blood pressure encephalopathy;
2. Patients with grade I or higher myocardial ischemia or myocardial infarction,
arrhythmia (including QTc interval >450ms for men and >470ms for women) and
congestive heart failure =2 (New York Heart Association (NYHA) classification),
severe /Unstable angina) and patients who have undergone coronary/peripheral
artery bypass surgery;
3. Active or uncontrolled serious infection (=CTCAE grade 2 infection), and those
who are known to have active tuberculosis;
4. Renal failure requires hemodialysis or peritoneal dialysis
5. Liver diseases such as liver cirrhosis, decompensated liver disease, chronic
active hepatitis;
6. Poor control of diabetes (fasting blood glucose (FBG)>10mmol/L);
7. Urine routine test shows that urine protein is =++, and the 24-hour urine protein
quantification is confirmed to be >1.0 g;
- Long-term unhealed wounds or fractures;
- Patients with symptoms of hematemesis, hematochezia and daily bleeding =2.5mL, or any
bleeding event =CTCAE level 3 within 3 months before screening, or any bleeding signs
or medical history judged by the investigator to be unsuitable regardless of the
severity Enrolled patients; or patients with abnormal coagulation function (INR>1.5 or
prothrombin time (PT)>ULN+4 seconds or APTT>1.5 ULN), have bleeding tendency or are
receiving thrombolytic or anticoagulant therapy; Note: Under the premise that the
international normalized ratio of prothrombin time (INR) = 1.5, the use of low-dose
heparin (daily dosage for adults is 6,000 to 12,000 U) or low-dose aspirin (daily
dosage = 100 mg);
- A history of gastrointestinal perforation and/or fistula in the 6 months before the
enrollment treatment; or arterial/venous thrombotic events, such as cerebrovascular
accidents (including temporary ischemic attacks), deep vein thrombosis and lungs
Embolizer
- Central nervous system metastases and/or cancerous meningitis with symptoms or active
stages are known to exist;
- Ascites with clinical significance, including any ascites that can be found on
physical examination, ascites that has been treated in the past or that still needs to
be treated, and only those with a small amount of ascites but asymptomatic on imaging
can be selected;
- Patients with moderate effusion in both pleural cavities, or large effusion in one
pleural cavity, or patients who have caused respiratory dysfunction and need drainage;
- Suffer from interstitial lung disease that requires steroid therapy;
- Uncontrolled metabolic disorders or secondary reactions of other non-malignant tumor
organs or systemic diseases or cancers, which may lead to higher medical risks and/or
uncertainty in survival evaluation;
- Those who have a history of psychotropic drug abuse and cannot be quit or have mental
disorders;
- Have a history of immunodeficiency, including those who have tested positive for HIV
or have other acquired or congenital immunodeficiency diseases, or have a history of
organ transplantation;
- History of other primary malignant tumors, except for the following: a) Malignant
tumors that have been completely remitted for at least 2 years before enrollment and
no other treatment is required during the study period; b) Non-melanoma skin that has
been adequately treated and has no evidence of disease recurrence Carcinoma or
malignant freckle-like nevus; c) Carcinoma in situ that has been adequately treated
and has no evidence of disease recurrence;
- Any of the following immune-related medical history and treatment history:
1. There is any active autoimmune disease or a history of autoimmune disease (the
following but not limited to: autoimmune hepatitis, interstitial pneumonia,
enteritis, vasculitis, nephritis; subjects who require bronchodilators for
medical intervention Asthma cannot be included); but the following patients are
allowed to be included in the group: vitiligo, psoriasis, hair loss without
systemic treatment, well-controlled type I diabetes, and hypothyroidism with
normal thyroid function after replacement therapy;
2. Diagnosed with immunodeficiency or are receiving systemic glucocorticoid therapy
or any other form of immunosuppressive therapy (dose>10mg/day of prednisone or
other curative hormones), and remain within 2 weeks before the first
administration Continuing to use
3. Have received any live vaccines, attenuated vaccines (including anti-infective
vaccines, such as flu vaccines, varicella vaccines, etc.) or inactivated vaccines
within 4 weeks before enrollment, and plan to vaccinate live vaccines/attenuated
vaccines/inactivated vaccines during the study period Vaccine; used systemic
immunostimulatory agents (including but not limited to interferon and IL-2)
within 2 weeks before the start of the study treatment;
- During pregnancy or lactation, or planning to become pregnant during the study period
or within 3 months after the last administration of TQB2450 or Anlotinib;
- According to the judgment of the investigator, there is a concomitant disease that
seriously endangers the safety of the patient or affects the patient to complete the
study.
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