| Eligibility |
Inclusion Criteria:
- Male or female aged = 18 and<80 years old.
- The ECOG score is 0-1 points (including 0 and 1 points), and the expected survival
period is not less than 3 months.
- Confirmed as small cell lung cancer (SCLC) by histopathology or cytology and diagnosed
as extensive after systemic evaluation.
- I have not received first-line treatment for ES-SCLC systemic chemotherapy or immune
checkpoint inhibitors in the past.
- Limited stage SCLC progresses to extensive stage SCLC after receiving previous
radiotherapy and chemotherapy aimed at cure,at least 6 months of no treatment period
is required after the last radiotherapy and/or chemotherapy treatment.
- Patients with previous active brain metastases have stabilized after treatment and do
not require immediate or planned brain intervention during the study period Transfer
for local treatment.
- According to the criteria for evaluating the efficacy of solid tumors (RECIST v1.1),
enrolled patients should have at least one tumor throughout their body The tumor
lesion can meet the following requirements: it has not undergone local treatment such
as radiotherapy in the past and is at baseline Can be accurately measured, with a
baseline maximum diameter of = 10mm (if it is a lymph node, a minimum diameter of =
15mm is required).
Lesions that have previously received local treatment (radiotherapy or other treatments),
if the treatment is completed for at least 6 months If disease progression occurs later,
the lesion in the area that has undergone local treatment can be considered a measurable
lesion.
- Patients should have sufficient bone marrow reserve function and no liver, kidney, or
coagulation dysfunction, and laboratory tests should be conducted
- The value must meet the following conditions:
1. Absolute neutrophil count = 1.5 × 109/L, and white blood cell count = 3 × 109/L;
2. Platelet count = 100 × 109/L;
3. Hemoglobin = 90g/L;
4. Serum creatinine (Cr) = 1.5 x Upper limit of normal (ULN) or creatinine clearance
rate (CrCl) = 50ml/min (for patients with serum creatinine>1.5 x ULN);
5. If there is no confirmed liver metastasis, AST and ALT = 2.5 × ULN; If there is
confirmed liver metastasis, AST,ALT = 5 × ULN;
6. If there is no confirmed liver metastasis, total bilirubin = 1.5 × ULN; If there
is confirmed liver metastasis or patients with syndrome (high indirect
bilirubinemia), total bilirubin = 3 x ULN;
7. If there is no confirmed liver metastasis, alkaline phosphatase (ALP) = 2.5 x ULN
or = 5 x ULN (bone metastasis)
8. Albumin (ALB)>30g/dl;
9. 24-hour urine protein quantification<1g (if urine protein = 2+, additional
24-hour urine protein testing is required)
10. Serum lipase or amylase = 1.5 x ULN or>1.5 x ULN (clinical or imaging diagnosis
of pancreas)
11. International standardized ratio (INR) = 1.5, and activated partial prothrombin
time (APTT)= 1.5 x ULN.
- Female subjects with reproductive ability have a negative blood pregnancy result
within 7 days before starting the study treatment, and are willing to From the time of
signing the informed consent form until the end of the last medication use, abstain
from sexual activity or take medication for a period of 6 months medically recognized
and efficient contraceptive measures (such as intrauterine devices, condoms, etc.),
but the use of hormones is prohibited Using similar drugs for contraception; Male
subjects are willing to take informed consent from the time of signing until the end
of the last medication use Within the next 6 months, abstain from sexual activity or
use medically recognized and effective contraceptive measures (such as condoms),and
during this period, no sperm will be donated;.
- The subjects are able to understand and voluntarily sign a written informed consent
form (the informed consent form must be completed before conducting the study) Sign
before any program specified in the plan.
- Be able to voluntarily complete the research procedures and follow-up examinations
according to the requirements of the research protocol.
Exclusion Criteria:
- Mixed small cell lung cancer diagnosed by histology or cytology;
- A history of severe allergic diseases, severe drug (including unmarketed
investigational drugs) allergies, or known adverse reactions to this medication
Allergy to any component of the investigational drug: presence of etoposide, platinum
based drugs (carboplatin/cisplatin), or anlotinib.Individuals who are contraindicated
to the use of anlotide or Toripalimab;
- Previously received treatment with immune checkpoint agonists (such as CD137 agonists)
or immune checkpoint inhibitors.Preparation therapy (such as single/dual antibodies
against CTLA-4, PD-1, PD-L1, LAG3, etc.) or anti VEGF targeted drugs;
- Previously received curative radiotherapy (excluding those who met the inclusion
criteria of 5), or before receiving study treatment.Has undergone extensive palliative
radiotherapy within 4 weeks, or plans to undergo chest radiotherapy during the study
period
- Need or plan to undergo elective surgical treatment during the trial period;
- Received the following treatments or medications before starting the research
treatment:
1. Received important organ surgery (excluding puncture) within 28 days before
starting the study and treatment Inspection;
2. Received attenuated live vaccine within 28 days prior to starting treatment;
3. Have used intravenous broad-spectrum antibiotics for at least 7 days within 14
days before starting the study treatment;
4. Starting the study on systemic corticosteroids (prednisone>10) received within 14
days prior to treatment Mg/day or equivalent dose of similar drugs or other
immunosuppressive treatments; Except for the following situations External:
Treatment with local, ocular, intra-articular, intranasal, and inhaled
corticosteroids; short Regular use of glucocorticoids for preventive treatment
(such as preventing contrast agent allergies);
5. Received palliative radiotherapy for bone metastases within 14 days prior to
starting the study treatment;
- Currently, there is spinal cord compression or superior vena cava syndrome;
- Currently, there are clear cases of interstitial lung disease or non infectious
pneumonia, except for those caused by local radiotherapy;
- There are brain metastases in the midbrain, pons, medulla oblongata, spinal cord,
meninges, and meninges, or symptomatic large brain metastases Brain or cerebellar
metastasis (such as manifested as cerebral edema and/or progressive growth); Central
nervous system conversion
Individuals limited to the brain and cerebellum can participate in screening if they meet
the following conditions:
a. Asymptomatic brain metastases (asymptomatic central nervous system progressive symptoms
caused by brain metastases, also not necessary) Using corticosteroids or antiepileptic
drugs for treatment; b. Symptoms stabilize for at least 2 weeks after radiotherapy for
brain metastases, and corticosteroids or antiepileptic drugs are discontinued Drug
discontinuation for at least 2 weeks;
- Evidence of significant coagulation disorders or other significant bleeding risks:
1. History of intracranial hemorrhage or spinal cord hemorrhage;
2. Patients with tumor lesions invading large blood vessels and having a significant
risk of bleeding;
3. Within the 6 months prior to the start of the study treatment, there have been
incidents of thrombosis or embolism (asymptomatic and none) Except for
intramuscular venous thrombosis that requires treatment, there is no absorption
during follow-up examination, or significant vascular disease is present (For
aortic aneurysm, aortic dissection, etc. that require surgical repair);
4. Clinically significant hemoptysis or tumor development for any reason within the
first 3 months prior to starting the study treatment Blood;
5. Within 14 days prior to the start of the study, use anticoagulant therapy for
therapeutic purposes (with low prophylactic use) Excluding molecular weight
heparin;
- Past or current active autoimmune diseases or immunodeficiency, including but not
limited to severe muscle disease Weakness, myositis, autoimmune hepatitis, systemic
lupus erythematosus, rheumatoid arthritis, inflammation Sexually transmitted bowel
disease, antiphospholipid antibody syndrome, Wegener's granulomatosis, Sj ö gren
syndrome, Grimm Barr syndrome Li syndrome or multiple sclerosis; Except for: a
Autoimmune related hypothyroidism Subjects with a history of withdrawal and currently
taking thyroid replacement hormone; b. Stable status receiving insulin treatment 30%
of subjects with type I diabetes.
- Lesions limited to subjects with eczema, psoriasis, chronic simple lichen, and
vitiligo on the skin (if diseased)
When the damage has already affected parts or organs outside the skin (such as psoriasis,
arthritis, etc.), it cannot be included in the group:
i. Fever of unknown origin>38.5 ? (fever caused by tumor can be included in the group);
- Within 6 months prior to starting the study of drug therapy, the following situations
occurred:
1. Suffering from congestive heart failure, severe/unstable angina, cerebrovascular
accident, New York, USA Cardiac insufficiency classified by the Society of
Cardiology (NYHA) as Grade II or above (including Grade II), Or other structural
heart diseases that have been determined by researchers to be at high risk;
2. History of abdominal fistula, tracheoesophageal fistula, gastrointestinal
perforation, or abdominal abscess;
3. There is uncontrollable tumor related pain, and if painkillers are needed, they
should be stable during screening A prescribed pain relief treatment plan;
Asymptomatic metastatic lesions, if further grown, may lead to Causing functional
impairment or stubborn pain (such as epidural metastases that are currently
unrelated to spinal cord compression), If appropriate, local treatment should be
considered before screening;
- Within the 5 years prior to starting the research on drug therapy, if there were other
active malignant tumors, local treatment may be necessary Except for malignant tumors
that have been treated and cured (such as basal cell or squamous cell carcinoma of the
skin, superficial or non malignant) Invasive bladder cancer cancer, cervical carcinoma
in situ, breast intraductal carcinoma in situ, thyroid papillary carcinoma);
- Individuals who have received allogeneic hematopoietic stem cell transplantation or
organ transplantation in the past;
- Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency
syndrome (AIDS);
- Syphilis antibody positive and active syphilis infection present;
- Individuals with active pulmonary tuberculosis or a history of pulmonary tuberculosis
infection that cannot be controlled after treatment;
- 20 HBsAg or HBcAb positive, and HBV-DNA>2000 IU/mL (for For patients with HBV DNA>500
IU/mL, the subject must agree to at least 7 days prior to the start of the study drug
Continuously receiving antiviral treatment other than interferon during the research
period is necessary to participate in screening; HCV antibodies Positive and HCV-RNA
higher than the lower limit of detection in the experimental center (if the center is
unable to detect HCV) RNA, acceptable external hospital results, relevant reports
should be provided);
- Expected to receive any other form of anti-tumor drug treatment during the trial
period;
- Known to have a history of alcohol abuse, psychotropic substance abuse, or drug use;
- Individuals with mental disorders or poor compliance;
- Pregnant or lactating women
- According to the judgment of the researchers, the basic condition of the subjects may
increase their risk of receiving study drug treatment,Or confusion caused by the
occurrence of toxic reactions and the explanation of AE;
- Other researchers deemed it unsuitable to participate in this experiment;
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