A Single-Arm, Exploratory Clinical Study of Benmelstobart Combined With Anlotinib and Chemotherapy Concurrent With Thoracic Radiotherapy as First-Line Treatment in Limited-Stage Small Cell Lung Cancer (LS-SCLC)
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 27
- 主要终点
- Investigator-Assessed Objective Response Rate
研究概览
简要总结
This is a single-arm, single-center, exploratory clinical study conducted at Shanghai Pulmonary Hospital, Tongji University. The study evaluates the effectiveness and safety of first-line treatment with benmelstobart (an immunotherapy), anlotinib (an anti-angiogenic drug), platinum-etoposide chemotherapy, and concurrent thoracic radiotherapy in participants with previously untreated, unresectable limited-stage small cell lung cancer (LS-SCLC).
Eligible participants are aged 18 to 75 years, with histologically or cytologically confirmed limited-stage SCLC (VALG staging), no prior systemic treatment for lung cancer, measurable lesions by RECIST 1.1, ECOG performance status 0-1, and adequate organ function.
Participants receive 4 cycles of induction therapy (21 days per cycle), including benmelstobart intravenously every 3 weeks, anlotinib orally for 2 weeks on / 1 week off, and chemotherapy with carboplatin or cisplatin plus etoposide. Thoracic radiotherapy (60-70 Gy in 30-35 fractions) is given concurrently with chemotherapy cycles 1-3. After induction, participants receive maintenance therapy with benmelstobart plus anlotinib for up to 2 years or until disease progression or unacceptable side effects.
The primary objective is to assess the Objective Response Rate (ORR) as evaluated by investigators using RECIST 1.1. Secondary objectives include progression-free survival (PFS), overall survival (OS), disease control rate (DCR), duration of response (DOR), and safety assessments of adverse events graded by CTCAE 5.0.
A total of 27 participants will be enrolled. The study is expected to start in March 2026, complete enrollment by September 2027, and end in March 2029. All participants will be regularly followed for efficacy and safety.
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
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 limited-stage small cell lung cancer (LS-SCLC) (per VALG staging).
- •2: No prior systemic therapy for limited-stage small cell lung cancer
- •3: Presence of measurable lesions as defined by RECIST 1.
- •A previously irradiated lesion may be considered measurable only if it has demonstrated clear progression after radiotherapy and is not the sole lesion
- •4: Age ≥ 18 and ≤ 75 years
- •5: ECOG performance status: 0-1
- •6: Expected survival ≥ 3 months
- •7: Adequate hematologic and organ function, defined as meeting the following criteria: a) Hematologic function (no transfusion of blood or blood products, no G-CSF or other hematopoietic growth factors within 14 days): 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 (CrCl) ≥ 50 mL/min; ii. Urine protein < 2+ or 24-hour urine protein quantification < 1.0 g. c) Hepatic function: i. Serum total bilirubin (TBil) ≤ 1.5 × ULN; ii. AST and ALT ≤ 2.5 × 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%.
- •8: Subjects voluntarily participate in this study, provide written informed consent, demonstrate good compliance, and agree to comply with follow-up procedures.
排除标准
- •1: Prior use of anti-angiogenic agents such as anlotinib, apatinib, bevacizumab, or related immunotherapeutic agents targeting PD-1, PD-L1, etc
- •2: Presence of multiple factors affecting oral medication absorption (e.g., inability to swallow, status post gastrointestinal resection, chronic diarrhea, intestinal obstruction, etc.).
- •3: Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage.
- •4: Patients with imaging evidence of tumor invasion adjacent to major blood vessels, or judged by the investigator to have a high risk of fatal massive hemorrhage due to tumor invasion of major blood vessels during the subsequent study period.
- •5: History of severe bleeding tendency or coagulopathy, including but not limited to: clinically significant hemoptysis (more than one tablespoon per day) within 3 months prior to enrollment; or clinically significant bleeding symptoms or bleeding diathesis within 4 weeks prior to randomization, such as gastrointestinal bleeding, hemorrhagic gastric ulcer (including gastrointestinal perforation and/or fistula; however, patients with surgically repaired gastrointestinal perforation or fistula may be eligible), unhealed wounds, ulcers, or fractures, etc.
- •6: Undergoing major surgical treatment, incisional biopsy, or significant traumatic injury within 28 days prior to randomization.
- •7: History of arterial/venous thrombotic events within 6 months prior to randomization, such as cerebrovascular accident (including transient ischemic attack), deep vein thrombosis, and pulmonary embolism.
- •8: Development of active autoimmune disease requiring systemic therapy (e.g., disease-modifying agents, corticosteroids, or immunosuppressants) within 2 years prior to the first dose.
- •9: Any other conditions that, in the judgment of the investigator, would render the patient ineligible for study enrollment.
研究组 & 干预措施
Benmelstobart combined with anlotinib and chemotherapy concurrent with thoracic radiotherapy
Benmelstobart combined with anlotinib plus chemotherapy concurrent with thoracic radiotherapy for limited-stage small cell lung cancer.
Benmelstobart Injection: 1200 mg/dose, Q21D (1 cycle), IV infusion. Anlotinib Hydrochloride Capsules: 12 mg/day, oral (2 weeks on/1 week off, repeated Q3W), taken with water at fixed time.
Chemotherapy:
Carboplatin: Day 1, AUC 5 mg/mL/min (max 750 mg), IV infusion; Cisplatin: Day 1, 75-80 mg/m², IV infusion; Etoposide: Days 1-3, 100 mg/m², IV infusion. Concurrent Thoracic Radiation: Initiated with Cycle 1 of chemotherapy; IMRT, 60-70 Gy in 30-35 fractions (1.8-2.0 Gy/fraction, once daily); target volumes: primary tumor + lymph nodes delineated on post-chemotherapy CT, investigator-adjusted individually.
干预措施: Thoracic Radiation Therapy (Radiation)
Benmelstobart combined with anlotinib and chemotherapy concurrent with thoracic radiotherapy
Benmelstobart combined with anlotinib plus chemotherapy concurrent with thoracic radiotherapy for limited-stage small cell lung cancer.
Benmelstobart Injection: 1200 mg/dose, Q21D (1 cycle), IV infusion. Anlotinib Hydrochloride Capsules: 12 mg/day, oral (2 weeks on/1 week off, repeated Q3W), taken with water at fixed time.
Chemotherapy:
Carboplatin: Day 1, AUC 5 mg/mL/min (max 750 mg), IV infusion; Cisplatin: Day 1, 75-80 mg/m², IV infusion; Etoposide: Days 1-3, 100 mg/m², IV infusion. Concurrent Thoracic Radiation: Initiated with Cycle 1 of chemotherapy; IMRT, 60-70 Gy in 30-35 fractions (1.8-2.0 Gy/fraction, once daily); target volumes: primary tumor + lymph nodes delineated on post-chemotherapy CT, investigator-adjusted individually.
干预措施: Cisplatin or carboplatin (Drug)
Benmelstobart combined with anlotinib and chemotherapy concurrent with thoracic radiotherapy
Benmelstobart combined with anlotinib plus chemotherapy concurrent with thoracic radiotherapy for limited-stage small cell lung cancer.
Benmelstobart Injection: 1200 mg/dose, Q21D (1 cycle), IV infusion. Anlotinib Hydrochloride Capsules: 12 mg/day, oral (2 weeks on/1 week off, repeated Q3W), taken with water at fixed time.
Chemotherapy:
Carboplatin: Day 1, AUC 5 mg/mL/min (max 750 mg), IV infusion; Cisplatin: Day 1, 75-80 mg/m², IV infusion; Etoposide: Days 1-3, 100 mg/m², IV infusion. Concurrent Thoracic Radiation: Initiated with Cycle 1 of chemotherapy; IMRT, 60-70 Gy in 30-35 fractions (1.8-2.0 Gy/fraction, once daily); target volumes: primary tumor + lymph nodes delineated on post-chemotherapy CT, investigator-adjusted individually.
干预措施: Benmelstobart (Drug)
Benmelstobart combined with anlotinib and chemotherapy concurrent with thoracic radiotherapy
Benmelstobart combined with anlotinib plus chemotherapy concurrent with thoracic radiotherapy for limited-stage small cell lung cancer.
Benmelstobart Injection: 1200 mg/dose, Q21D (1 cycle), IV infusion. Anlotinib Hydrochloride Capsules: 12 mg/day, oral (2 weeks on/1 week off, repeated Q3W), taken with water at fixed time.
Chemotherapy:
Carboplatin: Day 1, AUC 5 mg/mL/min (max 750 mg), IV infusion; Cisplatin: Day 1, 75-80 mg/m², IV infusion; Etoposide: Days 1-3, 100 mg/m², IV infusion. Concurrent Thoracic Radiation: Initiated with Cycle 1 of chemotherapy; IMRT, 60-70 Gy in 30-35 fractions (1.8-2.0 Gy/fraction, once daily); target volumes: primary tumor + lymph nodes delineated on post-chemotherapy CT, investigator-adjusted individually.
干预措施: Anlotinib (Drug)
Benmelstobart combined with anlotinib and chemotherapy concurrent with thoracic radiotherapy
Benmelstobart combined with anlotinib plus chemotherapy concurrent with thoracic radiotherapy for limited-stage small cell lung cancer.
Benmelstobart Injection: 1200 mg/dose, Q21D (1 cycle), IV infusion. Anlotinib Hydrochloride Capsules: 12 mg/day, oral (2 weeks on/1 week off, repeated Q3W), taken with water at fixed time.
Chemotherapy:
Carboplatin: Day 1, AUC 5 mg/mL/min (max 750 mg), IV infusion; Cisplatin: Day 1, 75-80 mg/m², IV infusion; Etoposide: Days 1-3, 100 mg/m², IV infusion. Concurrent Thoracic Radiation: Initiated with Cycle 1 of chemotherapy; IMRT, 60-70 Gy in 30-35 fractions (1.8-2.0 Gy/fraction, once daily); target volumes: primary tumor + lymph nodes delineated on post-chemotherapy CT, investigator-adjusted individually.
干预措施: Etoposide (Drug)
结局指标
主要结局
Investigator-Assessed Objective Response Rate
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
According to RECIST 1.1 criteria, investigator assesses target lesion changes via imaging; calculates the proportion of subjects achieving complete response (CR) or partial response (PR)
次要结局
- Serious Adverse Event (SAE)(from date of first study drug administration, follow-up until resolution or stabilization, assessed up to approximately 24 months)
- 6-Month Progression-Free Survival Rate(6-month time point after first treatment, follow-up cutoff)
- 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.)
- Progression-Free Survival (PFS)(From date of first study drug administration until the date of first documented disease progression (per RECIST v1.1) or death from any cause, whichever occurs first; assessed up to 24 months (maximum follow-up period).)
- 18-Month Overall Survival Rate(18-month time point after first treatment, follow-up cutoff)
- 12-Month Overall Survival Rate(12-month time point after first treatment, follow-up cutoff)
- 12-Month Progression-Free Survival Rate(12-month time point after first treatment, follow-up cutoff)
- 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)
- 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)
- 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)
- Adverse Event (AE)(From signing informed consent through study completion and safety follow-up, assessed up to approximately 24 months)
研究者
Yayi He
Professor
Shanghai Pulmonary Hospital, Shanghai, China