Neoajuvant Tislelizumab Combined with Chemotherapy for Initially Unresectable Stage IIIA/N2 Non-small Cell Lung Cancer

Prospective Phase II Trial of Neoajuvant Tislelizumab Combined with Chemotherapy for Initially Unresectable Stage IIIA/N2 Non-small Cell Lung Cancer

To investigate the efficacy and safety of neoadjuvant treatment with Tislelizumab combined with chemotherapy for initially unresectable N2/III non-small cell lung cancer.

Study Overview

• Status: Not yet recruiting
• Conditions: NSCLC, Stage IIIA; NSCLC (non-small Cell Lung Cancer)
• Intervention / Treatment: Drug: Tislelizumab Combined With Chemotherapy

Detailed Description

This study is a prospective, single-arm, single-center phase II clinical trial to investigate the efficacy and safety of neoadjuvant treatment with tirilizumab in combination with chemotherapy in patients with initially inoperable stage III/N2 non-small cell lung cancer.

Patients with stage III/N2 non-small cell lung cancer that is initially inoperable and clearly staged and meets the enrollment criteria will receive 3 cycles of tirilizumab (200 mg) in combination with chemotherapy and will be evaluated by imaging of their tumor status. After MDT evaluation patients will either undergo surgery or be withdrawn from the study and receive a combination of radiotherapy and chemotherapy, with postoperative adjuvant therapy at the discretion of the physician. The primary endpoint of this study is the surgical conversion rate; secondary endpoints include MPR, pCR, safety, and EFS.

• Study Type: Interventional
• Enrollment (Estimated): 48
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xue Hou, MD; Phone Number: +86-13570569436; Email: houxue@sysucc.org.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Patients with initially untreated, unresectable stage III NSCLC (according to the International Association for the Study of Lung Cancer IASLC 8th Thoracic Tumor Stage) with non-small cell lung cancer
2. All patients received baseline PET/CT (or neck, upper thoracic and abdominal CT+ cranial MR) for clinical staging
3. Cytology/histology (mediastinoscopy or EBUS, etc.) confirmed N2 non-small cell lung cancer
4. For non-squamous cell carcinoma patients, if EGFR/ALK mutation status is unknown, tissue samples should be provided for EGFR/ALK gene testing before enrollment; For patients with squamous cell carcinoma, if EGFR/ALK mutation status is unknown, testing is not required during screening
5. ECOG (Performance status, PS) score 0-1

6. Hematology testings meet the following requirements

   • neutrophil ≥1.5*109/L
   • Platelets ≥100*109/L
   • Hemoglobin > 9.0 g/dL
   • Serum creatinine ≤1.5ULN or creatinine clearance (Ccr) ≥40mL/min
   • AST/ALT≤ 3ULN
   • Total bilirubin ≤1.5ULN
   • FEV1≥1.2L or > 40% of the estimated value
   • INR/APTT within normal range
7. The patient is over 18 years old
8. Measurable lesions (according to the RECIST 1.1 version)
9. Subject must understand and voluntarily sign informed consent prior to any study-related evaluation

Exclusion Criteria

1. The patient presents with a confirmed or suspected autoimmune disorder.

   • Note: Patients with vitiligo, type I diabetes mellitus, or Hashimoto's thyroiditis who are hypothyroid but require only hormone replacement therapy may be included in the study if there are no obvious signs of relapse

2. Patients must have undergone systemic corticosteroid treatment (≥10mg prednisolone [or equivalent]/day) or received other immunosuppressive medications within 14 days prior to enrollment.

   • Note: Inhaled or topical corticosteroids and adrenal hormone replacement therapy (≥10mg prednisolone [or equivalent]/day) can also be accepted for individuals lacking clear evidence of autoimmune disorders
3. Patients with grade 3 or 4 interstitial lung disease
4. Have other malignant tumors and need anti-tumor therapy
5. Patients with previous malignancies (except skin malignancies other than melanoma, and in situ cancers of the following sites (bladder, stomach, colorectal, endometrial, cervix, melanoma, or breast) were not included in the study. Unless the malignancy has been in complete remission for two years or more and no additional antitumor therapy is required during the study period
6. The investigator believes that the patient is medically, psychologically, or physically incapable of completing this study or of understanding the patient handbook information
7. Previously received anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA, and other drugs targeting T-cell co-stimulation or immune regulatory pathways
8. Presence of active Hepatitis B or C
9. HIV-positive or diagnosed with Acquired Immune Deficiency Disease (AIDS)
10. Allergy to the study drug
11. Women who are pregnant or breastfeeding

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: Tislelizumab; Tislelizumab 200mg Q3W	Drug: Tislelizumab Combined With Chemotherapy; Tislelizumab 200mg Q3W，Platinum-containing dual drug chemotherapy; Other Names: Platinum-containing

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Surgical conversion rate	After 3 cycles of Tislelizumab combined with chemotherapy, the number of patients who underwent surgical resection/number of patients enrolled	Within 4-6 weeks (+7 days) after the third cycle of Tislelizumab combined with chemotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major pathologic response(MPR)	Less than 10% of tumor cells remained in the pathological excision specimen	Within one week after surgery
Pathologic Complete response（pCR）	No tumor cells were observed in pathological excision specimens	Within one week after surgery

Collaborators and Investigators

• Sponsor: Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Estimated): September 20, 2024
• Primary Completion (Estimated): September 8, 2028
• Study Completion (Estimated): September 8, 2028

Study Registration Dates

• First Submitted: September 12, 2024
• First Submitted That Met QC Criteria: September 23, 2024
• First Posted (Actual): September 26, 2024

Study Record Updates

• Last Update Posted (Actual): September 26, 2024
• Last Update Submitted That Met QC Criteria: September 23, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: Neoadjuvant treatment; Unresectable stage III NSCLC; Tirellizumab
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Antineoplastic Agents; Antineoplastic Agents, Immunological; Tislelizumab
• Other Study ID Numbers: B2024-446-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: publish an article

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