Radiation Therapy Followed by Tislelizumab and Anlotinib Aeoadjuvant/Adjuvant Therapy for Stage II-IIIA NSCLC

NCT06379087 | Recruiting Phase 2

• 1 other identifier: NEO-PIONEER
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a single-center, prospective, single-arm exploratory clinical study of hypofractionated radiotherapy followed by tislelizumab and anlotinib neoadjuvant and adjuvant therapy. It is designed for patients with stage II-IIIA non-small cell lung cancer. The efficacy and safety of hypofractionated radiotherapy sequential tislelizumab and anlotinib in the neoadjuvant and adjuvant treatment of stage II-IIIA non-small cell lung cancer are observed. Finally, it provides new evidence-based medical evidence for the perioperative treatment of non-small cell lung cancer.

Conditions

Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• pCR Rate

  Complete pathological response (pCR), defined as the proportion of patients in the ITT analysis set and surgical population analysis set who have no residual tumor in the resected primary tumor and metastatic lymph nodes as assessed by the investigator after the completion of neoadjuvant therapy. Patients who do not meet these criteria, including those who do not undergo surgical resection, will be considered non-responders.

  12 months

Secondary Outcomes (3)

• 1-year EFS Rate

  Baseline up to 1 years

• MPR Rate

  12 months

• Adverse Events (AEs) according to CTCAE (V5.0) (Safety Evaluation)

  Baseline up to 3 years

Study Arms (1)

Single Arm

EXPERIMENTAL

Neoadjuvant therapy regimen (2 cycles): 1. Receive 3-day hypofractionated treatment on Day 1, Day 2, and Day 3, with a total dose of 24Gy (8Gy\*3). 2. Within 1 week after radiotherapy, receive neoadjuvant tislelizumab (200 mg, intravenous drip, d1) combined with anlotinib (10 mg, oral, D1-14) . Each 3 weeks is a medication cycle. Surgical protocol: The surgical approach was determined by the surgeon according to the patient's condition, including but not limited to thoracoscopic/open lobectomy/sleeve lobectomy/combined lobectomy/pneumonectomy. Lymph node dissection requires at least three stations of mediastinal lymph node dissection. Adjuvant therapy regimen: tislelizumab (200 mg, intravenous drip, d1) combined with Anlotinib (10 mg, oral, D1-14). Each 3 weeks is a medication cycle, for 1 year.

Drug: Anlotinib Hydrochloride Capsule; Drug: Tislelizumab Injection; Radiation: Hypofractionated Radiotherapy

Interventions

Anlotinib Hydrochloride Capsule DRUG

Anlotinib hydrochloride is a muti-target tyrosine kinase inhibitor that inhibits both tumor angiogenesis and tumor cell proliferation by blocking VEGFR, FGFR, PDGFR, and c-Kit simultaneously.

Also known as: Anlotinib

Single Arm

Tislelizumab Injection DRUG

Tislelizumab is a humanized IgG4 anti-PD-1 monoclonal antibody.

Also known as: Tislelizumab

Single Arm

Hypofractionated Radiotherapy RADIATION

Hypofractionated Radiotherapy Extent of radiotherapy: Primary lesion in the lung. Radiotherapy technique: IGRT. Radiotherapy delivery equipment: linear accelerator or TOMO accelerator or CyberKnife.

Single Arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• (1) Aged 18-75 years old;
• (2) Early stage II-IIIA NSCLC (AJCC 8th edition), NSCLC, confirmed in tissue (AJCC eighth edition);
• (3) All lesions are assessed to be eligible for surgical resection;
• (4) The primary tumor can be treated with hypofractionated radiotherapy after evaluation;
• (5) Epidermal growth factor receptor/anaplastic lymphoma kinase/ROS1 gene fusions mutation was negative in primary tumor or lymph node metastasis;
• (6) ECOG PS score: 0\~1;
• (7) Expected survival more than 1 year;
• (8) At least one measurable lesion (RECIST 1.1);
• (9) Females of childbearing potential should agree to use contraceptive measures (such as intrauterine device, contraceptives or condoms) during the study and within 3 months after the end of the study; have a negative serum or urine pregnancy test within 7 days before study enrollment and must be non-lactating subjects; and males should agree to use contraceptive measures during the study and within 3 months after the end of the study period;
• (10) Subjects voluntarily participate in this study, sign the informed consent form and had good compliance;
• (11) Subjects are suitable after MDT discussion.

You may not qualify if:

• Participants with any of the following criteria were excluded from the trial:
• (1) The location of the primary tumor was assessed by the radiologist and considered unsuitable for hypofractionated therapy;
• (2) The pathological type is small cell lung cancer, or mixed tumor with small cell components;
• (3) A history of or concurrent with other malignancies;
• (4) Received any anti-tumor treatment before this study, including chemotherapy, radiotherapy, targeted therapy (including but not limited to monoclonal antibodies, small molecule tyrosine kinase inhibitors, etc.) and immunotherapy;
• (5) The Imaging (CT/MR/PET-CT) showed tumor invasion of great vessels or blurred boundary with blood vessels, or the presence of any pulmonary cavity or necrotic lesions;
• (6) Hemoptysis, active bleeding, ulcer, intestinal perforation, intestinal obstruction within 3 months before enrollment;
• (7) Previous interstitial lung disease, drug-induced interstitial disease or any clinical evidence of active interstitial lung disease; baseline CT scan found idiopathic pulmonary fibrosis;
• (8) According to the investigator's judgment, there are serious or uncontrollable systemic diseases (such as unstable or uncompensated respiratory, cardiac, hepatic or renal diseases) or any unstable systemic diseases (including active infection, grade III hypertension, unstable angina, congestive heart failure, liver and kidney or metabolic diseases);
• (9) Previous treatment with anti-PD-1, anti-PD-L1 or anti-PD-L2 drugs or drugs acting on another co-inhibitory T cell receptor (e.g., CTLA-4, OX-40, CD137);
• (10) The presence of uncontrollable third space effusion, such as a large number of pleural effusion or ascites or pericardial effusion;
• (11) Urine routine showed urine protein ≥ + +, or 24h urine protein ≥ 1g or severe liver and kidney dysfunction;
• (12) Uncontrollable hypertension (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg);
• (13) Subjects requiring systemic treatment with corticosteroids (\> 10 mg/day prednisone or equivalent) or other immunosuppressive agents within 14 days before the first dose;
• (14) Hyperactive/venous thrombotic events occurred within 6 months, such as cerebrovascular accident (including cerebral hemorrhage, cerebral infarction, temporary ischemic attack, etc.);

Sponsors & Collaborators

• Ji Yongling: lead

Study Sites (1)

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

anlotinib; tislelizumab; Radiation Dose Hypofractionation

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Dose Fractionation, Radiation; Radiotherapy Dosage; Radiotherapy; Therapeutics

Study Officials

• YongLing Ji, PhD

  Zhejiang Cancer Hospital

  STUDY DIRECTOR

Central Study Contacts

Min Fang, PhD

CONTACT

13738152645; fangmin0114@126.com

YongLing Ji, PhD

CONTACT

13958085251; jiyl@zjcc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Physician

Study Record Dates

• First Submitted: April 11, 2024
• First Posted: April 23, 2024
• Study Start: May 1, 2024
• Primary Completion: December 31, 2025
• Study Completion (Estimated): December 31, 2026
• Last Updated: July 10, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)