A Study of Adebrelimab Combined With Apatinib Mesylate and Chemotherapy for Neoadjuvant Therapy and Biomarker Analysis in Limited-stage Small Cell Lung Cancer

A Single-arm, Prospective, Exploratory Study of Adebrelimab Combined With Apatinib Mesylate and Chemotherapy for Neoadjuvant Therapy and Biomarker Analysis in Limited-stage Small Cell Lung Cancer

This is a single-arm, prospective, exploratory phase II clinical study. The study enrolled newly diagnosed stage T1-3N0-1M0 resectable limited-stage small cell lung cancer. Adebrelimab combined with chemotherapy for 4 cycles and apatinib mesylate for 3 cycles. Surgery was performed within 4-8 weeks after the above treatment (the operation was performed 4 weeks after apatinib was discontinued). According to the results of MDT discussion, adebrelimab combined with apatinib mesylate combined with or without radiotherapy was started 4 weeks after surgery. Preoperative prophylactic radiotherapy (PCI) is recommended for patients with preoperative stage N1. Patients with postoperative stage N1 received postoperative thoracic radiotherapy.

Study Overview

• Status: Recruiting
• Conditions: Small Cell Lung Cancer Limited Stage
• Intervention / Treatment: Drug: Adebrelimab; Drug: Apatinib Mesylate; Drug: Etoposide; Drug: Carboplatin

Detailed Description

Preoperative prophylactic radiotherapy (PCI) is recommended for patients with preoperative stage N1. Patients with postoperative stage N1 received postoperative thoracic radiotherapy.

• Study Type: Interventional
• Enrollment (Estimated): 38
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ying Jin, MD&Phd; Phone Number: 86+18806529092; Email: jinying@zjcc.org.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Recruiting
      • Zhejiang Cancer Hospital
      • Contact: Ying Jin, MD&Phd; Phone Number: 86+18806529092; Email: jinying@zjcc.org.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age between 18 and 75 years old;
• Histologically or cytologically confirmed limited-stage small cell lung cancer (T1-3N0-1M0).
• All lesions of the patient (including the primary lesion, lymph nodes/lesions assessed as metastatic) must be jointly evaluated and confirmed as resectable by a surgeon, a radiation oncologist, and a radiologist;
• The subject must have measurable target lesions (according to RECIST 1.1 criteria);
• ECOG performance status score of 0-1;
• No history of other malignancies;
• No previous treatment for small cell lung cancer-related surgery, radiotherapy, chemotherapy, immunotherapy, or other anti-tumor treatments;
• The patient must have adequate cardiopulmonary function: the patient's FEV1 and DLCO are both ≥50% of the predicted value, echocardiography shows LVEF ≥55%, and no clear signs of heart failure, severe coronary artery stenosis, etc., are seen on various tests, and the cardiopulmonary function is assessed by a surgeon as being able to tolerate surgical treatment;
• The levels of important organ functions must meet the following requirements: a. Bone marrow: Absolute neutrophil count (ANC) ≥1.5×10^9/L, platelets ≥100×10^9/L, hemoglobin ≥9 g/dl; b. Good coagulation function: defined as international normalized ratio (INR) or prothrombin time (PT) ≤1.5 times the upper limit of normal (ULN); c. Liver: Total bilirubin ≤1.5 times the upper limit of normal, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 times the upper limit of normal; d. Kidney: Serum creatinine ≤1.25 times the upper limit of normal or creatinine clearance (calculated using the Cockcroft-Gault formula) ≥60 ml/min;
• Males with reproductive capacity and women of childbearing age must agree to use effective contraception from the time of signing the main informed consent form until 180 days after the last administration of the study drug. Women of childbearing age include pre-menopausal women and post-menopausal women within 2 years. The pregnancy test result of women of childbearing age must be negative within ≤7 days before the first administration of the study drug;
• Voluntarily participate in clinical research; fully understand and be informed about this study and sign the informed consent form.

Exclusion Criteria:

• Inability to completely remove all lesions through surgery;
• Received anti-tumor treatment for SCLC (including but not limited to chemotherapy, radiotherapy of the lesion area).
• Previously used immunocheckpoint inhibitors such as PD-1/PD-L1 inhibitors for treatment.
• Any history of active autoimmune diseases or autoimmune diseases (such as uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, myocarditis, nephritis, hyperthyroidism, hypothyroidism (can be included after hormone replacement therapy), tuberculosis); patients with childhood asthma that has completely resolved and does not require any intervention in adulthood or vitiligo can be included, but patients requiring medical intervention with bronchodilators are not eligible for inclusion;
• Have congenital or acquired immune system deficiencies, such as human immunodeficiency virus (HIV) infected individuals, active hepatitis B (HBV DNA ≥ 500 IU/ml), hepatitis C (positive for hepatitis C antibodies and HCV-RNA is above the lower limit of detection of the analytical method) or co-infection with both hepatitis B and C;
• Existence of uncontrollable third-space effusions, such as a large amount of pleural effusion or ascites or pericardial effusion;
• Subjects who need systemic treatment with corticosteroids (>10 mg/day prednisone or equivalent) or other immunosuppressants within 14 days before the first administration of the drug. Inhaled or topical corticosteroids are allowed, as well as adrenal hormone replacement therapy with a dose >10 mg/day prednisone equivalent, in the absence of active autoimmune diseases;
• Subjects who have been treated with anti-tumor vaccines or other immunostimulatory anti-tumor drugs (interferons, interleukins, thymosin, immune cell therapy, etc.) within 1 month before the first administration of the drug;
• Currently participating in other interventional clinical studies;
• Evidence of previous or current pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-induced pneumonia, and severe lung function impairment;
• Patients with severe heart disease, such as congestive heart failure grade III or above (NYHA standard), or angina grade III or above (CCS standard), or a history of myocardial infarction within 6 months before treatment initiation, or arrhythmias requiring drug treatment;
• Major surgery, open biopsy, or significant trauma within 28 days before enrollment;
• Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation;
• Pregnant or breastfeeding women; patients with fertility who are unwilling or unable to take effective contraceptive measures;
• Known allergic reactions, hypersensitivity, or intolerance to the study drug;
• Hypertension that cannot be well controlled with antihypertensive drug treatment (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg);
• Abnormal coagulation function (INR > 2.0 or prothrombin time (PT) > 16s), with a tendency to bleed or currently undergoing thrombolysis or anticoagulant treatment (preventive use of low-dose aspirin, low molecular weight heparin is allowed);
• Significant clinical bleeding symptoms within the last 3 months or a clear tendency to bleed, such as gastrointestinal bleeding, bleeding gastric ulcers, or patients with vasculitis, etc., if the baseline fecal occult blood is positive, it can be retested, and if it is still positive after retesting, an endoscopy is required (except for those who have undergone endoscopy within 3 months and before the baseline period to rule out such conditions);
• Arterial/venous thrombotic events within the last 6 months, such as cerebrovascular accidents (including transient ischemic attacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism;
• Known genetic or acquired bleeding and thrombotic tendencies (such as hemophilia, coagulation disorders, thrombocytopenia, etc.). Other conditions deemed unsuitable for participating in the study by the researcher.

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: Adebrelimab in combination with chemotherapy and apatinib mesylate; Adebrelimab 1200mg q3w for 4 cycles, Apatinib mesylate 250mg qod q3w 3 times/week concurrent with adebrelimab for 3 cycles, platinum-based chemotherapy (etoposide, 100mg/m2, q3w; Carboplatin, AUC=5, q3w), 4 cycles, and operation was performed within 4-8 weeks after treatment (Apatinib mesylate was discontinued for 4 weeks). According to the results of MDT discussion, adebrelimab, 1200mg q3w, and apatinib 250mg qod q3w 3 times/week were used 4 weeks after surgery, which with or without radiotherapy. Preoperative prophylactic radiotherapy (PCI) is recommended for patients with preoperative stage N1. Patients with postoperative stage N1 received postoperative thoracic radiotherapy.

Drug: Adebrelimab; This product is administered by intravenously guttae. The recommended dose of subcutaneous injection is 20mg/kg, administered every 3 Weeks (Q3W).; Other Names: SHR-1316; Drug: Apatinib Mesylate; This product is an orally administered targeted therapy drug, with a recommended dosage of one tablet per day.; Drug: Etoposide; This product is administered by intravenously guttae. The recommended dose of subcutaneous injection is 100mg/m2, administered every 3 Weeks (Q3W).; Drug: Carboplatin; This product is administered by intravenously guttae. AUC=5, administered every 3 Weeks (Q3W).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
EFS of 2 years	The proportion of patients who did not experience any of the following events from the start of treatment to 2 years: disease progression without surgical treatment, local or distant recurrence, death from any cause, etc.	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pCR	pCR, Pathological Complete Response, defined as the complete absence of all tumor cells in the primary site and lymph nodes.	Up to 2 years
MPR	MPR (Major Pathological response,) was defined as residual tumor cells ≤10% in pathological examination of postoperative specimens.	Up to 2 years
EFS	EFS (Event-Free Survival) refers to the time from the beginning of randomization to the first occurrence of any of the following events: disease progression without surgical treatment, local or distant recurrence, death from any cause, etc.	Up to 2 years
OS	OS (Overall Survival), the time from the date of randomization until the death of the participant or the last follow-up.	Up to 2 years
ORR	ORR (Objective Response Rate) refers to the proportion of patients whose tumor shrinkage reaches a certain level and remains for a certain period of time, including complete response (CR) and partial response (PR) cases.	Up to 2 years
Treatment-Emergent Adverse Events [Safety and Tolerability]	Number of participants with treatment-related adverse events as assessed by NCI-CTCAE v5.0.	Up to 2 years

Collaborators and Investigators

• Sponsor: Jin Ying
• Investigators: Study Chair: Da Chen, MD&PhD, Medical Ethics Committee of Zhejiang Cancer Hospital; Principal Investigator: Zhengfu He, MD&PhD, Sir Run Run Shaw Hospital; Principal Investigator: Zhengliang Tu, MD&PhD, Zhejiang University; Principal Investigator: Junqiang Fan, MD&PhD, Second Affiliated Hospital, School of Medicine, Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): June 21, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: May 23, 2024
• First Submitted That Met QC Criteria: July 1, 2024
• First Posted (Actual): July 3, 2024

Study Record Updates

• Last Update Posted (Actual): April 15, 2025
• Last Update Submitted That Met QC Criteria: April 13, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Etoposide; Carboplatin; Apatinib
• Other Study ID Numbers: IRB-2024-420

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No