this is a two-cohort, exploratory clinical study assessing the activity of benmelstobart combined with chemotherapy with or without anlotinib in resectable limited-stage small cell lung cancer

Conditions: Limited Stage Small Cell Lung Cancer

Summary: a total of 66 patients were enrolled in this exploratory study and randomly assigned to cohort 1 and cohort 2, with 33 patients in each group. cohort 1: neoadjuvant therapy (benmelstobart combined with chemotherapy and anlotinib, 3 cycles, every 21 days is a cycle). surgery was performed 4-6 weeks after the final administration of benmelstobart as assessed by the investigator. adjuvant therapy was evaluated by the investigator 4-6 weeks after surgery. patients who achieved r0 resection received adjuvant therapy (benmelstobart combined with anlotinib, 12 cycles, every 21 days is a cycle). cohort 2: neoadjuvant therapy (benmelstobart combined with chemotherapy, 3 cycles, every 21 days is a cycle). surgery was performed 4-6 weeks after the final administration of benmelstobart as assessed by the investigator. adjuvant therapy was evaluated by the investigator 4-6 weeks after surgery. patients who achieved r0 resection received adjuvant therapy (benmelstobart, every 21 days is a cycle) .


Eligibility criteria:
inclusion criteria: * patients voluntarily participate in this study, sign the informed consent form, demonstrate good compliance, and cooperate with follow-up. * aged 18 to 75 years (inclusive) at the time of signing informed consent, regardless of gender. * histologically confirmed small cell lung cancer (sclc). * confirmed as stage i-iiib sclc (t1-3n0-2m0) per ajcc 9th edition. * patients who have received 1 cycle of chemotherapy are eligible; no other prior treatments are permitted. * ecog performance status (ps) 0 or 1. * assessed by the investigator as having no surgical contraindications. * at least one measurable lesion per recist 1.1 criteria. * expected survival ≥8 weeks. * women of childbearing potential (aged 15-49) must have a negative serum pregnancy test within 7 days before treatment initiation and agree to use reliable contraception during the study until 8 weeks after discontinuation. normal function of major organs meeting the following criteria: * hematologic tests (no blood transfusion, blood products, g-csf, or hematopoietic stimulants within 14 days): hemoglobin (hb) ≥90 g/l; absolute neutrophil count (anc) ≥1.5×10⁹/l; platelets (plt) ≥80×10⁹/l. * biochemical tests meeting: total bilirubin (tbil) ≤1.5×uln; alt/ast ≤2.5×uln; serum creatinine (cr) ≤1.5×uln or creatinine clearance (ccr) ≥60 ml/min. * urine protein \<2+; for patients not on anticoagulation: inr ≤1.5, aptt ≤1.5×uln. patients on full-dose or parenteral anticoagulants may enroll if dosing has been stable for ≥2 weeks and coagulation tests are within therapeutic ranges. exclusion criteria: * histologically confirmed mixed-type sclc. * extensive-stage sclc. * ecog ps \>1. * active or untreated cns metastases confirmed by ct/mri during screening/prior imaging. * uncontrolled tumor-related pain. * uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage (≥1×/month). * uncontrolled/symptomatic hypercalcemia (ionized calcium \>1.5 mmol/l, calcium \>12 mg/dl, or corrected serum calcium \>uln). * systemic immunostimulants (e.g., ifn-α, il-2, tnf) within 4 weeks prior to enrollment (cancer vaccines allowed if prior). * systemic corticosteroids (\>10 mg prednisone/day or equivalent) or immunosuppressants within 14 days, except: replacement therapy (≤10 mg prednisone/day); topical/ocular/intra-articular/nasal/inhaled steroids with minimal systemic absorption; short-term (≤7 days) prophylactic use (e.g., contrast allergy) or for non-autoimmune conditions. * imaging-confirmed tumor invasion of major vessels or high risk of fatal hemorrhage per investigator; or cavitary/necrotic lung tumors. * other malignancies within 5 years except: cervical cis, cured basal cell carcinoma, ta/tis bladder tumors. * prior use of anlotinib or other antiangiogenic agents. * prior anti-pd-1/pd-l1/ctla-4 antibodies or other t-cell co-stimulation/checkpoint pathway therapies (e.g., icos, cd40/cd137/gitr/ox40 agonists). * hypersensitivity to anlotinib or benmelstobart components. * factors impairing oral drug intake (e.g., dysphagia, chronic diarrhea, intestinal obstruction). * uncontrolled comorbidities including: 1. poorly controlled hypertension (sbp ≥150 mmhg, dbp ≥100 mmhg); 2. grade ≥1 myocardial ischemia/infarction, arrhythmias (qtc ≥480 ms), or ≥nyha class ii heart failure; 3. abnormal coagulation (inr \>1.5, pt \>uln+4s, aptt \>1.5×uln), bleeding tendency, or thrombolytic/anticoagulant therapy (prophylactic low-dose heparin \[6,000-12,000 u/day\] or aspirin \[≤100 mg/day\] allowed if inr ≤1.5); 4. active/severe uncontrolled infections; 5. cirrhosis, decompensated liver disease, active/chronic hepatitis requiring antivirals; 6. renal failure requiring dialysis; 7. immunodeficiency (hiv+, congenital/acquired immunodeficiency) or organ transplant history; 8. poorly controlled diabetes (fbg \>10 mmol/l); 9. urine protein ≥++ or 24-h urine protein \>1.0 g; 10. epilepsy requiring treatment; 11. non-healing wounds/fractures. * significant hemoptysis (\>50 ml/day within 2 weeks) or clinically significant bleeding (e.g., gi bleeding, hemorrhagic gastric ulcer, baseline fecal occult blood ≥++). * interstitial lung disease (ild), drug-induced ild, steroid-requiring radiation pneumonitis, or active ild. * arterial/venous thromboembolism within 6 months (e.g., stroke \[including tia\], dvt, pe). * grade ≥2 peripheral neuropathy (excluding trauma-related). * major surgery/severe trauma with residual effects within 14 days. * concurrent clinical trials or \<4 weeks from prior trial treatment. * live/attenuated vaccination within 30 days before benmelstobart or planned during study. * history of severe hypersensitivity to monoclonal antibodies. * pregnant/lactating women. * uncontrolled psychiatric/neurological disorders affecting compliance. * other factors per investigator judgment that may lead to study termination (e.g., severe illness, lab abnormalities, or social/family constraints compromising safety/data collection).