Perioperative Treatment With Benmelstobart Combined With Chemotherapy With or Without Anlotinib in Resectable Limited-Stage Small Cell Lung Cancer: A Randomized, Two-Cohort, Multicenter, Phase II Clinical Study
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 66
- 主要终点
- event-free survival (EFS)
研究概览
简要总结
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) .
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
盲法说明
Masking Description
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •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.
排除标准
- •Histologically confirmed mixed-type SCLC.
- •Extensive-stage SCLC.
- •ECOG PS >
- •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:
- •Poorly controlled hypertension (SBP ≥150 mmHg, DBP ≥100 mmHg);
- •Grade ≥1 myocardial ischemia/infarction, arrhythmias (QTc ≥480 ms), or ≥NYHA Class II heart failure;
- •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);
- •Active/severe uncontrolled infections;
- •Cirrhosis, decompensated liver disease, active/chronic hepatitis requiring antivirals;
- •Renal failure requiring dialysis;
- •Immunodeficiency (HIV+, congenital/acquired immunodeficiency) or organ transplant history;
- •Poorly controlled diabetes (FBG >10 mmol/L);
- •Urine protein ≥++ or 24-h urine protein >1.0 g;
- •Epilepsy requiring treatment;
- •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).
研究组 & 干预措施
Cohort 1: Neoadjuvant therapy (benmelstobart combined with chemotherapy and anlotinib)
Cohort 1: Neoadjuvant therapy (benmelstobart combined with chemotherapy and anlotinib, 3 cycles, every 21 days is a cycle) : benmelstobart, 1200mg, iv, day 1. Anlotinib, 10 mg, po, qd, was taken orally for 2 consecutive weeks and stopped for 1 week. Anlotinib was stopped 1 week before surgery. Etoposide, 100mg/m2, day 1~3. Cisplatin, 75mg/m2，day 1; or Carboplatin, AUC 5, day 1. 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) : benmelstobart, 1200mg, iv, day1; anlotinib, 10 mg, po, qd, was taken orally for 2 weeks and stopped for 1 week.
干预措施: benmelstobart combined with chemotherapy and anlotinib (Drug)
Cohort 2: Neoadjuvant therapy (benmelstobart combined with chemotherapy)
Cohort 2: Neoadjuvant therapy (benmelstobart combined with chemotherapy, 3 cycles, every 21 days is a cycle) : benmelstobart, 1200mg, iv, day1; Etoposide, 100mg/m2, day 1~3; Cisplatin, 75mg/m2，day 1; or Carboplatin, AUC 5, day 1. 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) : benmelstobart, 1200mg, iv, day1.
干预措施: benmelstobart combined with chemotherapy (Drug)
结局指标
主要结局
event-free survival (EFS)
时间窗: up to 2 years
The event-free survival (EFS) is defined as the duration from randomization to the occurrence of any event, which includes disease progression, postoperative recurrence, discontinuation of treatment for any reason, or death.
次要结局
- Major pathologic response rate (MPR)(7 days after surgery)
- Complete pathological response (pCR)(7 days after surgery)
- Objective response rate (ORR)(7 days after surgery)
- overall survival (OS)(up to 3 year)
- Treatment-related adverse events evaluated according to CTCAE v5.0(up to 2 years)
- Surgical complications evaluated according to the Clavien-Dindo classification(up to 2 years)