A Single-arm, Exploratory Clinical Study of Benmelstobart Combined With Anlotinib and Chemotherapy Followed by Thoracic Radiotherapy as First-line Treatment for Extensive-stage Small Cell Lung Cancer (ES-SCLC)
概览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- Yayi He
- 入组人数
- 33
- 主要终点
- Objective Response Rate (ORR)
概览
简要总结
This is a single-center, single-arm, exploratory clinical study conducted at Shanghai Pulmonary Hospital, Tongji University. It aims to evaluate the efficacy and safety of first-line treatment with benmelstobart plus anlotinib and chemotherapy (carboplatin/cisplatin plus etoposide), followed by sequential thoracic radiotherapy, in patients with previously untreated extensive-stage small cell lung cancer (ES-SCLC).
Eligible participants will be adults aged 18-75 years with histologically or cytologically confirmed ES-SCLC, measurable lesions per RECIST 1.1, ECOG performance status 0-1, and adequate organ function. Patients will receive 4 cycles of induction therapy (benmelstobart, anlotinib, platinum-etoposide chemotherapy). Those without disease progression will receive consolidative thoracic radiotherapy, followed by maintenance therapy with benmelstobart plus anlotinib until disease progression or unacceptable toxicity.
The primary endpoint is objective response rate (ORR) assessed by investigators. Secondary endpoints include progression-free survival (PFS), overall survival (OS), disease control rate (DCR), duration of response (DOR), and safety parameters including adverse events graded by CTCAE 5.0. A total of 33 subjects will be enrolled. This study uses a non-randomized, open-label design without a control group.
详细描述
This is a single-center, single-arm, prospective, exploratory clinical trial to evaluate the efficacy and safety of first-line benmelstobart combined with anlotinib and platinum-etoposide chemotherapy, followed by sequential thoracic radiotherapy, in patients with untreated extensive-stage small cell lung cancer (ES-SCLC).
Eligible patients will receive 4 cycles of 21-day induction therapy consisting of intravenous benmelstobart 1200 mg on day 1, oral anlotinib 12 mg once daily for 2 weeks on / 1 week off, plus carboplatin (AUC 5) or cisplatin (75-80 mg/m²) on day 1 and etoposide 100 mg/m² on days 1-3 of each cycle. Patients without disease progression after induction therapy will receive consolidative thoracic radiotherapy (2 Gy per fraction, 25-30 fractions). Maintenance therapy with benmelstobart plus anlotinib will be administered until disease progression, unacceptable toxicity, or a maximum of 2 years.
The primary outcome is investigator-assessed objective response rate (ORR) per RECIST 1.1. Secondary outcomes include progression-free survival (PFS), overall survival (OS), disease control rate (DCR), duration of response (DOR), and safety assessed by adverse events (AE, SAE, irAE) graded according to CTCAE version 5.0. A total of 33 subjects will be enrolled.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
盲法说明
This is an open-label study with no masking applied to any parties involved in the trial.
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
- •1: Histologically or cytologically confirmed inoperable extensive-stage small cell lung cancer (ES-SCLC) according to the VALG staging system
- •2: No prior systemic therapy for extensive-stage small cell lung cancer (ES-SCLC)
- •3: Presence of measurable lesions as defined by the RECIST 1.1 criteria. A previously irradiated lesion can be considered measurable only if there is clear progression after radiotherapy and it is not the sole lesion
- •4: Aged 18 to 75 years
- •5: ECOG performance status score of 0 to 1
- •6: Expected survival time ≥ 3 months
- •7: Number of tumor metastases ≤
- •Brain metastases must be asymptomatic or treated and stable for at least 1 month prior to the initiation of study treatment, with no use of steroids or anticonvulsants during this period
- •8: Adequate hematological and organ function, meeting the following criteria: a) Hematology (no blood transfusion or blood products within 14 days; no correction with G-CSF or other hematopoietic stimulants): i. Absolute Neutrophil Count (ANC) ≥ 1.5 × 10⁹/L (1,500/mm³); ii. Platelet Count (PLT) ≥ 100 × 10⁹/L (100,000/mm³); iii. Hemoglobin (HB) ≥ 80 g/L. b) Renal function: i. Calculated Creatinine Clearance Rate (CrCl) ≥ 50 mL/min; ii. Urine protein \< 2+ or 24-hour urinary protein quantitation \< 1.0 g. c) Hepatic function: i. Serum Total Bilirubin (TBil) ≤ 1.5 × ULN (for patients with liver metastases, TBil ≤ 3 × ULN); ii. AST and ALT ≤ 2.5 × ULN (for patients with liver metastases, ≤ 5 × ULN); iii. Serum Albumin (ALB) ≥ 28 g/L. d) Coagulation function: i. International Normalized Ratio (INR) and Activated Partial Thromboplastin Time (APTT) ≤ 1.5 × ULN. e) Cardiac function: i. Left Ventricular Ejection Fraction (LVEF) ≥ 50%. f) Other: i. Lipase ≤ 1.5 × ULN; patients with lipase \> 1.5 × ULN may be enrolled if there is no clinical or radiological evidence of pancreatitis; ii. Amylase ≤ 1.5 × ULN; patients with amylase \> 1.5 × ULN may be enrolled if there is no clinical or radiological evidence of pancreatitis; iii. Alkaline Phosphatase (ALP) ≤ 2.5 × ULN (for patients with bone metastases, ALP ≤ 5 × ULN
- •9: The subject voluntarily agrees to participate in the study, signs the informed consent form, has good compliance, and is willing to cooperate with follow-up
排除标准
- •1: Patients with symptomatic brain metastases. Patients whose brain metastases have been treated and remain clinically stable for at least 1 month, with no use of steroids or anticonvulsants for at least 1 month prior to study enrollment, are eligible
- •2: Prior use of anti-angiogenic agents such as anlotinib, apatinib, bevacizumab, or immune checkpoint inhibitors targeting PD-1, PD-L1, etc
- •3: Patients with conditions that affect oral drug administration (e.g., dysphagia, post-gastrointestinal resection, chronic diarrhea, intestinal obstruction, etc.)
- •4: Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage
- •5: Patients with radiological evidence of tumor invasion around major blood vessels, or those judged by the investigator to be at high risk of fatal massive hemorrhage due to potential tumor invasion of major blood vessels during the study
- •6: History of severe bleeding tendency or coagulation disorders, including but not limited to: clinically significant hemoptysis (≥ 1 tablespoon per day) within 3 months prior to enrollment; or clinically significant bleeding symptoms or tendency within 4 weeks prior to group assignment, such as gastrointestinal bleeding, hemorrhagic gastric ulcer (including gastrointestinal perforation and/or fistula; patients with gastrointestinal perforation or fistula that has been surgically resected are eligible), unhealed wounds, ulcers, or fractures, etc
- •7: Receipt of major surgical treatment, incisional biopsy, or significant traumatic injury within 28 days prior to group assignment
- •8: History of arterial/venous thrombotic events (e.g., cerebrovascular accident including transient ischemic attack, deep vein thrombosis, pulmonary embolism) within 6 months prior to group assignment
- •9: Active autoimmune disease requiring systemic treatment (e.g., disease-modifying antirheumatic drugs, corticosteroids, or immunosuppressants) within 2 years prior to the first dose of study drug
- •10: Other conditions that increase the risk associated with study participation or study drugs and, in the investigator's judgment, render the patient unsuitable for enrollment
研究组 & 干预措施
Benmelstobart + Anlotinib + Chemotherapy Followed by Thoracic Radiotherapy
Eligible patients receive 4 cycles of induction therapy (benmelstobart 1200mg IV D1 + anlotinib 12mg PO QD 2w-on/1w-off + carboplatin/cisplatin + etoposide). Non-progressive patients proceed to consolidative thoracic radiotherapy (2Gy/fraction, 25-30 fractions), followed by maintenance therapy with benmelstobart + anlotinib until disease progression or unacceptable toxicity.
干预措施: Anlotinib (Drug)
Benmelstobart + Anlotinib + Chemotherapy Followed by Thoracic Radiotherapy
Eligible patients receive 4 cycles of induction therapy (benmelstobart 1200mg IV D1 + anlotinib 12mg PO QD 2w-on/1w-off + carboplatin/cisplatin + etoposide). Non-progressive patients proceed to consolidative thoracic radiotherapy (2Gy/fraction, 25-30 fractions), followed by maintenance therapy with benmelstobart + anlotinib until disease progression or unacceptable toxicity.
干预措施: Etoposide (Drug)
Benmelstobart + Anlotinib + Chemotherapy Followed by Thoracic Radiotherapy
Eligible patients receive 4 cycles of induction therapy (benmelstobart 1200mg IV D1 + anlotinib 12mg PO QD 2w-on/1w-off + carboplatin/cisplatin + etoposide). Non-progressive patients proceed to consolidative thoracic radiotherapy (2Gy/fraction, 25-30 fractions), followed by maintenance therapy with benmelstobart + anlotinib until disease progression or unacceptable toxicity.
干预措施: Thoracic Radiotherapy (Radiation)
Benmelstobart + Anlotinib + Chemotherapy Followed by Thoracic Radiotherapy
Eligible patients receive 4 cycles of induction therapy (benmelstobart 1200mg IV D1 + anlotinib 12mg PO QD 2w-on/1w-off + carboplatin/cisplatin + etoposide). Non-progressive patients proceed to consolidative thoracic radiotherapy (2Gy/fraction, 25-30 fractions), followed by maintenance therapy with benmelstobart + anlotinib until disease progression or unacceptable toxicity.
干预措施: benmelstobart (Drug)
Benmelstobart + Anlotinib + Chemotherapy Followed by Thoracic Radiotherapy
Eligible patients receive 4 cycles of induction therapy (benmelstobart 1200mg IV D1 + anlotinib 12mg PO QD 2w-on/1w-off + carboplatin/cisplatin + etoposide). Non-progressive patients proceed to consolidative thoracic radiotherapy (2Gy/fraction, 25-30 fractions), followed by maintenance therapy with benmelstobart + anlotinib until disease progression or unacceptable toxicity.
干预措施: Carboplatin or cisplatin (Drug)
结局指标
主要结局
Objective Response Rate (ORR)
时间窗: Baseline at screening, after every 2 treatment cycles (each cycle is 21 days), end of treatment, up to disease progression, assessed up to approximately 24 months
Investigator-assessed ORR per RECIST 1.1 in ES-SCLC patients treated with benmelstobart plus anlotinib and chemotherapy followed by thoracic radiotherapy.
次要结局
- Progression-Free Survival (PFS)(Date of first study treatment to date of disease progression or death from any cause, last follow-up, assessed up to approximately 24 months)
- Overall Survival (OS)(From date of first study treatment to date of death from any cause or last follow-up, whichever occurs first, assessed up to approximately 24 months)
- 6-Month Progression-Free Survival Rate(6-month time point after first treatment, follow-up cutoff)
- Serious Adverse Event (SAE)(from date of first study drug administration , follow-up until resolution or stabilization, assessed up to approximately 24 months)
- Adverse Event (AE)(From signing informed consent through study completion and safety follow-up, assessed up to approximately 24 months)
- 18-Month Overall Survival Rate(18-month time point after first treatment, follow-up cutoff)
- Duration of Response (DOR)(From date of first confirmed objective response (CR/PR) until date of disease progression, death from any cause, or initiation of new antitumor therapy, whichever occurs first, assessed up to approximately 24 months)
- 12-Month Progression-Free Survival Rate(12-month time point after first treatment, follow-up cutoff)
- 12-Month Overall Survival Rate(12-month time point after first treatment, follow-up cutoff)
- Disease Control Rate (DCR)(Time Frame: Baseline and after every 2 treatment cycles (each cycle is 21 days), up to disease progression, death, or study withdrawal, whichever occurs first，assessed up to approximately 24 months)
- Immune-Related Adverse Event (irAE)(From date of first study drug administration through 90 days after the last dose of study drug; assessed at baseline, each cycle visit, and unscheduled visits for suspected irAEs; graded per CTCAE 5.0 and irAE-specific criteria.)
研究者
Yayi He
Professor
Shanghai Pulmonary Hospital, Shanghai, China