A Prospective, Single-arm, Phase II Clinical Study of Tislelizumab Combined With Anlotinib and Platinum-based Doublet Perioperative Therapy for Resectable Stage II-IIIB Driver Gene-negative NSCLC

NCT06977828 | Not Yet Recruiting Phase 2

• 1 other identifier: 2025-SR-259
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn if tislelizumab in combination with anlotinib and platinum-based doublet chemotherapy works to treat for resectable stage II-IIIB driver gene-negative NSCLC. It will also learn about the safety of tislelizumab in combination with anlotinib and platinum-based doublet chemotherapy. The main questions it aims to answer are:

1. 1.Does tislelizumab combined with anlotinib and platinum-based doublet perioperative therapy can increase pCR rate as well as MPR rate、EFS、DFS、ORR、OS for resectable stage II-IIIB driver gene-negative NSCLC?
2. 2.Is tislelizumab combined with anlotinib and platinum-based doublet perioperative therapy safe?

Conditions

NSCLC (Non-small Cell Lung Cancer); Neoadjuvant Immunotherapy; Adjuvant Immunotherapy

Outcome Measures

Primary Outcomes (1)

• Pathological Complete Response (pCR) rate

  Pathological complete response (pCR) is measured as the percentage of participants with a pathological complete response as assessed by the central pathologist at the time of definitive surgery. pCR is defined as having no residual invasive squamous cell carcinoma within the resected primary tumor specimen and all sampled regional lymph nodes.

  Up to ~64 months

Secondary Outcomes (6)

• Major Pathological Response (mPR) rate

  Up to ~64 months

• Event-free Survival (EFS)

  Up to ~80 months

• Disease-free survival (DFS)

  Up to ~80 months

• Objective response rate (ORR)

  Up to ~64 months

• Overall survival (OS)

  Up to ~92 months

Study Arms (1)

tislelizumab in combination with anlotinib and platinum-based doublet chemotherapy

EXPERIMENTAL

Drug: tislelizumab in combination with anlotinib and platinum-based doublet chemotherapy

Interventions

tislelizumab in combination with anlotinib and platinum-based doublet chemotherapy DRUG

After receiving 4 cycles of tislelizumab combined with anlotinib and platinum-based doublet chemotherapy, the subjects will be evaluated by a multidisciplinary team (MDT) to determine whether to proceed with radical surgical resection. The surgery will be performed within 3 to 7 weeks after the last neoadjuvant treatment. Postoperatively, patients will be divided into two subgroups based on the pathological results: For patients with postoperative pathological pCR, tislelizumab monotherapy will be used for maintenance treatment; For patients with postoperative pathological non-pCR, tislelizumab combined with anlotinib will be used for maintenance treatment. Both groups will continue treatment until disease progression, intolerable toxicity, withdrawal of informed consent, initiation of other anti-tumor therapy, death, or other situations specified in the protocol that require treatment cessation, whichever occurs first. The maximum treatment duration is 12 months

tislelizumab in combination with anlotinib and platinum-based doublet chemotherapy

Eligibility Criteria

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

You may qualify if:

• Fully understand and voluntarily sign the informed consent for this study;
• Age ≥18 years old and ≤75 years old, male or female;
• Patients with histologically or cytologically confirmed resectable stage II-IIIB non-small cell lung cancer;
• ECOG 0-1;
• No EGFR sensitive mutation, ALK or ROS1 fusion mutation was confirmed by tissue genetic testing before enrollment.
• Had not received any previous systemic treatment for non-small cell lung cancer;
• Patients with normal organ function within 7 days before enrollment met the following criteria:
• Blood routine test (no blood transfusion history within 14 days) :
• Hemoglobin (HB)≥90g/L; Absolute neutrophil count (ANC)≥1.5×109/L; j Platelet count (PLT)≥80×109/L.
• Biochemical test results met the following criteria:
• Total bilirubin (TBIL)≤1.5 ULN; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST)≤2.5 ULN, or 5 ULN if liver metastasis occurs; Serum creatinine (Cr)≤1.5 ULN or creatinine clearance (CCr)≥60mL/min. Left ventricular ejection fraction (LVEF)≥50%; Urine routine examination showed urine protein \< 2+ or 24-hour urine protein \< 1g; Serum amylase and lipase ≤ ULN.
• Male or female patients of childbearing potential voluntarily use an effective method of contraception, such as dual barrier methods, condoms, oral or injectable contraceptives, intrauterine devices, etc. during the study and for 6 months after the last study medication. All female patients will be considered fertile unless they have undergone natural menopause, artificial menopause, or sterilization (e.g., hysterectomy, bilateral adnophorectomy, or radioactive ovarian irradiation).

You may not qualify if:

• The pathological types of the patients were mixed with components of small cell lung cancer, neuroendocrine carcinoma, sarcoma, salivary gland tumor and mesenchymal tumor.
• Central, caenorrhea squamous cell carcinoma or hemoptysis non-small cell lung cancer (hemoptysis \>50 mL/ day);
• The tumor is surrounded by large blood vessels, and there is a potential risk of hemoptysis after anlotinib treatment;
• Presence of symptomatic or clinically significant thyroid dysfunction at screening (hypothyroidism controlled only with thyroid hormone replacement could be included);
• Patients who have been diagnosed with immunodeficiency or are receiving systemic glucocorticoid therapy or any other form of immunosuppressive therapy (prednisone at a dose of \>10mg/ day or other equivalent efficacy hormone) and continue to use it within 2 weeks before the first dose;
• Active autoimmune disease requiring systemic therapy (e.g., disease-modifying medications, corticosteroids, or immunosuppressive agents), including but not limited to inflammatory bowel disease such as ulcerative colitis or Crohn's disease, occurred within 2 years before enrollment; Diverticulitis; Celiac disease; Systemic lupus erythematosus; Sarcoidosis syndrome or Wegener syndrome (granulomatosis with polyangiitis); Graves' disease; Rheumatoid arthritis; Multiple sclerosis; Vasculitis; Glomerulonephritis; Antiphospholipid syndrome; Hypophysitis; Uveitis and so on. Alternative therapies (e.g., thyroxine, insulin, or physiological doses of corticosteroids for adrenal or pituitary insufficiency) were not considered systemic treatments. Patients who were positive for autoimmune antibodies were eligible for enrollment after investigator evaluation to confirm the absence of autoimmune disease requiring systemic treatment. ;
• Vaccination or attenuated vaccine within 4 weeks before enrollment;
• Received approved or investigational systemic anti-tumor therapy within 4 weeks before enrollment, including chemotherapy, radical radiotherapy, biological immunotherapy, targeted therapy, and traditional Chinese medicine therapy (traditional Chinese medicine therapy with clear indications for anti-tumor, after a 3-week washout period can also be enrolled);
• Participated in clinical trials of other drugs not yet approved or marketed in China and received treatment with corresponding drugs within 4 weeks before enrollment;
• Patients who underwent major surgery or unhealed wounds, ulcers, or fractures within 4 weeks before enrollment;
• International normalized ratio (INR) \>1.5 or activated partial prothrombin time (APTT) \>1.5×ULN; twelve Electrolyte abnormalities that were judged by the investigator to be clinically significant;
• Patients have drug-uncontrolled hypertension defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg;
• The patient has any current disease or condition that affects drug absorption or the patient is unable to take anlotinib orally;
• Patients with active gastric and duodenal ulcer, ulcerative colitis and other gastrointestinal diseases or unresected tumors with active bleeding, or other conditions that may cause gastrointestinal bleeding or perforation as judged by the investigators;
• Patients with evidence or history of significant bleeding tendency within 3 months before enrollment (bleeding \>30 mL within 3 months, hematemesis, melena, hematochezia), hemoptysis (\>5 mL of fresh blood within 4 weeks) or thromboembolic events (including stroke events and/or transient ischemic attack) within 12 months;

Sponsors & Collaborators

• The First Affiliated Hospital with Nanjing Medical University: lead

Study Sites (1)

The First Affiliated Hospital of Nanjing Medical University

Nanjing, Jiangsu, 210029, China

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

tislelizumab; anlotinib

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Lingxiang Lingxiang Liu, MD, Doctor of Medicine(M.D.)

CONTACT

86+13851892074; llxlau@163.com

Study Design

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

Study Record Dates

• First Submitted: May 11, 2025
• First Posted: May 18, 2025
• Study Start: July 20, 2025
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): December 31, 2028
• Last Updated: June 29, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)