A Study of Benmelstobart, Anlotinib, Chemotherapy and Thoracic Radiotherapy for People With Extensive-stage Small Cell Lung Cancer

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)

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.

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.

Inclusion Criteria:

• 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 ≤ 3. 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

Exclusion Criteria:

• 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