Carboplatin/Cisplatin + Etoposide + Benmelstobart Sequential Benmelstobart Combined With Anlotinib Versus Carboplatin/Cisplatin + Etoposide + Tislelizumab Sequential Tislelizumab in the Treatment of Extensive Stage Small Cell Lung Cancer

Inclusion Criteria:

• The subjects voluntarily joined the study, signed the informed consent, and had goodcompliance;

• 18 years old ≤age≤ 75 years old (calculated on the date of signing the informedconsent);

• Eastern Cooperative Oncology Group (ECOG) score 0 ~ 1;

• Expected survival greater than 12 weeks.

• Histologically or cytologically confirmed Extensive stage small cell lung cancer (ES-SCLC) (according to the Veterans Administration Lung Cancer Society (VALG)disease staging system).

• had not received systemic therapy for ES-SCLC (including systemic chemotherapy,molecular targeted drug therapy, biological therapy and other investigationaltherapeutic drugs, etc.) or immune checkpoint inhibitor therapy.

• Patients receiving chemoradiotherapy for previously limited-stage SCLC must betreated for cure, and there must be a treatment-free interval of at least 6 monthsfrom the last course of chemotherapy, radiotherapy, or chemoradiotherapy to thediagnosis of extensive SCLC.

• Confirmed presence of at least one measurable lesion according to RECIST 1.1criteria. Note: Measurable target lesions cannot be selected from previousradiotherapy sites. If the target lesion of the previous radiotherapy site is theonly alternative target lesion, the investigator should provide pre - andpost-imaging data showing significant progression of the lesion.

• Laboratory inspection meets the following standards:

1. Hemoglobin (HGB) ≥ 90g/L;

2. Neutrophil absolute value (NEUT) ≥ 1.5× 10 9 /L;

3. Platelet count (PLT) ≥ 90× 10 9 /L;

4. Total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal value (ULN);

5. Alanine transferase (ALT) and aspartate transferase (AST) ≤ 2.5×ULN. ALT andAST≤ 5×ULN if accompanied by liver metastasis;

6. Serum creatinine (CR) ≤ 1.5×ULN or creatinine clearance (CCR) ≥60 mL /min;

7. Prothrombin time (PT), activated partial thromboplastin time (APTT),International standardized ratio (INR) ≤ 1.5×ULN (no anticoagulant therapy).

• Women of reproductive age should agree that effective contraception must be usedduring the study period and for 6 months after the end of the study, and that serumor urine pregnancy tests are negative within 7 days prior to study enrollment; Menshould agree that effective birth control must be used during the study period andfor 6 months after the end of the study period.

Exclusion Criteria:

• Had or was currently suffering from other malignant tumors within 3 years prior tothe first medication. The following two conditions can be included: othermalignancies treated with a single operation, achieving continuous 5-yeardisease-free survival (DFS); Cured cervical carcinoma in situ, non-melanoma skincancer and superficial bladder tumors [Ta(non-invasive tumor), Tis (cancer in situ)and T1 (tumor infiltrating basal membrane)].

• The presence of diseases affecting intravenous administration, intravenous bloodcollection, or multiple factors affecting oral medication (such as inability toswallow, chronic diarrhea, and intestinal obstruction);

• The adverse effects of previous treatment did not return to The Common TerminologyCriteria for Adverse Events (CTCAE) v5.0 score ≤ 1, except for grade 2 alopecia,grade 2 peripheral neurotoxicity, grade 2 anemia, non-clinically significant andasymptomatic laboratory abnormalities, stable hypothyroidism after hormonereplacement therapy and other toxicities deemed by the investigators to be of nosafety risk.

• Those who have received major surgical treatment, significant traumatic injury, ormajor surgery during the intended study treatment period (other thanprotocol-specified surgery) within the 4 weeks prior to initial medication, or havesustained unhealed wounds or fractures. (Major surgery is defined as surgery atgrade 3 and above in the National Surgical Grading Directory 2022 edition).

• Subjects with any bleeding or bleeding event ≥ CTC AE grade 3 within 4 weeks priorto initial dosing.

• Patients who experienced a hyperarterial/venous thrombosis event, such ascerebrovascular accident (including transient ischemic attack), deep vein thrombosisand pulmonary embolism, within 6 months before the first administration of the drug.

• Active viral hepatitis and poorly controlled. Those who meet the followingrequirements can be screened: HBsAg positive subjects must meet Hepatitis B virus (HBV) DNA quantification <2000 IU/ml (or 1*104 copy/ml) or receive anti-HBV therapywith a 10-fold (1 log) or greater reduction in viral index for at least 1 week priorto study initiation, and subjects are willing to receive anti-HBV therapy throughoutthe study period; HCV infected persons (HCV Ab or HCV RNA positive) : Theinvestigators judged to be in a stable state or were receiving antiviral therapy atenrollment and continued to receive approved antiviral therapy in the study.

• Patients with active syphilis who need treatment;

• There is a history of active pulmonary tuberculosis, idiopathic pulmonary fibrosis,institutional pneumonia, drug-induced pneumonia, radiation pneumonia requiringtreatment, or active pneumonia with clinical symptoms.

• Those who have a history of psychotropic drug abuse and cannot quit or have mentaldisorders.

• People who are preparing for or have previously received allogeneic bone marrowtransplantation or solid organ transplantation.

• History of hepatic encephalopathy.

• Major cardiovascular disease, including any of the following:

1. According to the New York Heart Association (NYHA) standards of grade II orhigher cardiac insufficiency or heart color ultrasound: left ventricularejection fraction (LVEF) <50%;

2. There is a history of clinically significant ventricular arrhythmias (such aspersistent ventricular tachycardia, ventricular fibrillation, tip torsionventricular tachycardia) or arrhythmias requiring continuous antiarrhythmicdrug treatment;

3. Unstable angina;

4. Myocardial infarction occurred within 12 months;

5. Fridericia- modified QT interval (QTcF) > 450 ms (msec) for men and >470 msecfor women (if QTc is abnormal, it can be tested three times at intervals ofmore than 2 minutes, and its average value is taken);

6. Congenital long QT syndrome history or family history;

7. A history of deep vein thrombosis, pulmonary embolism, or any other severethromboembolism within the 3 months prior to randomization (implantable venousport or catheter-derived thrombosis, or superficial venous thrombosis is notconsidered "severe" thromboembolism);

8. Currently receiving or having recently received (within 7 days before the startof study treatment) aspirin (>325mg/ day (maximum antiplatelet dose) ordipyridamole, ticlopidine, clopidogrel, and cilostazol.

• Active or uncontrolled severe infection (≥CTC AE grade 2 infection);

• Patients with renal failure requiring hemodialysis or peritoneal dialysis;

• Have a history of immunodeficiency, including HIV positive or other acquired orcongenital immunodeficiency diseases;

• Subjects who require immunosuppressive, systemic, or absorbable topical hormonetherapy for immunosuppressive purposes and who continue to use it for 7 days priorto initial administration (except for corticosteroids < 10 mg daily prednisone orother therapeutic hormones);

• People who have epilepsy and need treatment.

• Tumor-related symptoms and treatment:

1. For subjects who have received chemotherapy, immunotherapy within 3 weeksbefore the first dose, radiation therapy or small molecule targeted drugswithin 2 weeks, or who are still within the 5 half-lives of the drug (as theshortest time of occurrence), the washout period is calculated from the endtime of the last treatment;

2. Within 2 weeks before the first drug use, it has been treated with Chinesepatent medicines (including compound Cantharides capsule, Kangai injection,Kanglaite capsule/injection, Aidi injection, Bruceae oil injection/capsule,Xiaoaiping tablet/injection, Cinobufotalin capsule, etc.) with anti-tumorindications specified in the National Medical Products Administration (NMPA)approved drug instructions;

3. Imaging (CT or MRI) shows that the tumor has invaded important blood vessels,or the investigator determines that the tumor is highly likely to invadeimportant blood vessels during the follow-up study period and cause fatalmassive bleeding;

4. Uncontrolled pleural effusion, pericardial effusion or moderate to severeascites that still require repeated drainage (investigators' judgment);

5. Patients with active central nervous system (CNS) metastases and/or cancerousmeningitis identified by known or screening tests. Subjects with asymptomaticbrain metastases (i.e., no progressive central nervous system symptoms causedby brain metastases, no need for corticosteroids, and the lesion size ≤1.5cm)can participate, but require regular brain imaging as a disease site. (2)Treated subjects with BMS who had stable BMS for at least 2 months (asdetermined by two imaging studies at least 4 weeks apart after BMS), noevidence of new or expanded BMS, and steroid discontinuation 3 days beforestudy drug administration. Stable brain metastases in this definition should bedetermined before the first administration of the investigational drug.

6. Spinal cord compression that was not treated radically by surgery and/orradiotherapy, or previously diagnosed spinal cord compression with no clinicalevidence of disease stabilization ≥1 week after treatment prior torandomization.

• Known allergy to study drug excipients, known severe allergic reaction to anymonoclonal antibody, history of carboplatin, cisplatin, or etoposide allergy.

• Subjects had previously been treated with other antibodies/drugs targeting immunecheckpoints, such as PD-1, PD-L1, CTLA4, etc.

• Previously received treatment with anti-angiogenic drugs such as Anlotinib,Apatinib, and Bevacizumab.

• Participants who had participated in and used other anti-tumor clinical trialswithin 4 weeks before the first medication.

• In the judgment of the investigator, there is a situation that seriously endangersthe safety of the subject or affects the completion of the study.