Benmelstobart Plus Anlotinib, Chemotherapy and Thoracic Radiation for Limited-Stage Small Cell Lung Cancer (Aurora004)

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)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Limited-stage Small Cell Lung Cancer (LS-SCLC)
• Intervention / Treatment: Drug: Benmelstobart; Drug: Anlotinib; Drug: Cisplatin or carboplatin; Drug: Etoposide; Radiation: Thoracic Radiation Therapy

• Study Type: Interventional
• Enrollment (Estimated): 27
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yayi He, MD; Phone Number: 021-65115006-2393; Email: yayi.he@tongji.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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 1.1. 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.

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

Drug: Benmelstobart; Anti-PD-L1 monoclonal antibody, immunotherapy.1200 mg/dose, Q21D (1 cycle), IV infusion.; Other Names: TQB2450; Andewei; Drug: Anlotinib; Small molecule multi-target anti-angiogenic agent.12 mg/day, oral (2 weeks on/1 week off, repeated Q3W), taken with water at fixed time.; Other Names: AL3818; Drug: Cisplatin or carboplatin; Chemotherapy agent.Carboplatin: Day 1, AUC 5 mg/mL/min (max 750 mg), IV infusion; Cisplatin: Day 1, 75-80 mg/m², IV infusion.; Drug: Etoposide; Chemotherapy agent. Days 1-3, 100 mg/m², IV infusion.; Radiation: Thoracic Radiation Therapy; External beam intensity-modulated radiotherapy (IMRT) targeting the primary thoracic tumor, ipsilateral hilum, and mediastinal lymph node stations (per LS-SCLC staging guidelines). 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Investigator-Assessed Objective Response Rate	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)	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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Time from first study treatment to death from any cause; censored at last follow-up for alive subjects	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	Estimated proportion of subjects without progression and alive at 6 months after first treatment using Kaplan-Meier method	6-month time point after first treatment, follow-up cutoff
Adverse Event (AE)	Record all new or worsening unfavorable medical events, grade and calculate incidence according to CTCAE 5.0	From signing informed consent through study completion and safety follow-up, assessed up to approximately 24 months
18-Month Overall Survival Rate	Estimated proportion of alive subjects at 18 months after first treatment via Kaplan-Meier method	18-month time point after first treatment, follow-up cutoff
Duration of Response (DOR)	Time from first confirmed CR/PR to disease progression, death from any cause, or initiation of new antitumor therapy	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	Estimated proportion of progression-free and alive subjects at 12 months via Kaplan-Meier method	12-month time point after first treatment, follow-up cutoff
12-Month Overall Survival Rate	Estimated proportion of alive subjects at 12 months after first treatment using Kaplan-Meier method	12-month time point after first treatment, follow-up cutoff
Disease Control Rate (DCR)	According to RECIST 1.1, proportion of subjects achieving CR, PR, or stable disease (SD) in total enrolled population	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)	Identify and grade organ-specific immune-related adverse events according to CTCAE 5.0 and irAE criteria	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.
Serious Adverse Event (SAE)	Collect SAEs resulting in death, life-threatening condition, hospitalization, disability per CTCAE 5.0 and ICH-GCP, document and report	from date of first study drug administration, follow-up until resolution or stabilization, assessed up to approximately 24 months
Progression-Free Survival (PFS)	Time from first treatment to disease progression or death from any cause, whichever occurs first	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).

Collaborators and Investigators

• Sponsor: Yayi He

Study record dates

Study Major Dates

• Study Start (Estimated): April 20, 2026
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): March 31, 2029

Study Registration Dates

• First Submitted: March 27, 2026
• First Submitted That Met QC Criteria: April 12, 2026
• First Posted (Actual): April 20, 2026

Study Record Updates

• Last Update Posted (Actual): April 20, 2026
• Last Update Submitted That Met QC Criteria: April 12, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: chemotherapy; anlotinib; Limited-stage small cell lung cancer; benmelstobart
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Small Cell Lung Carcinoma; Organic Chemicals; Hydrocarbons; Hydrocarbons, Cyclic; Carbohydrates; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Glucosides; Glycosides; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Coordination Complexes; Platinum Compounds; Etoposide; Carboplatin; Cisplatin; anlotinib
• Other Study ID Numbers: 2025LY12113; MR-31-26-022322 (Registry Identifier: Chinese Clinical Trial Registry (ChiCTR))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: The decision to share individual participant data (IPD) is currently undecided. This is an exploratory single-center clinical study, and IPD sharing will be re-evaluated after study completion and primary results analysis. Factors to be considered include the protection of participant privacy, compliance with ethical committee requirements, and the scientific validity of secondary research using the shared data. If IPD sharing is approved in the future, access will be provided in accordance with ClinicalTrials.gov guidelines and relevant regulatory requirements.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No