Clinical trial NCT06357598: Preoperative Neoadjuvant Immunotherapy Combined With Chemotherapy for Stage Ⅲ Unresectable Non-small Cell Lung Cancer
Official title: Preoperative Neoadjuvant Immunotherapy Combined With Chemotherapy for Newly Diagnosed Stage Ⅲ Unresectable Non-small Cell Lung Cancer: a Open-label, Single-arm Prospective Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Non-small-cell Lung Cancer (NSCLC)
Keywords: Non-small-cell Lung Cancer (NSCLC)
Immunotherapy
Chemotherapy
Lead sponsor: The Affiliated Hospital of Qingdao University
Sponsor class: OTHER
First posted: 2024-04-10
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Explorative study, which evaluates the effect of Tislelizumab combined with chemotherapy in neoadjuvant treatment of stage Ⅲ unresectable non-small-cell lung carcinoma.

Detailed description: This is a open-label, single-arm prospective clinical trial to evaluate the efficacy and safety of Tislelizumab combined with chemotherapy in neoadjuvant treatment of newly diagnosed stage Ⅲ unresectable non-small cell lung cancer.

Eligibility criteria: Inclusion Criteria:

1. Age :18 Years to 75 Years;
2. ECOG physical score status of 0 or 1 points;
3. Expected survival time ≥ 6 months;
4. According to the eighth edition of the AJCC/UICC TNM staging system, patients were pathological diagnosed with Stage III NSCLC and had one of the following conditions: 1) A complete resection (R0) would not be possible, based on evaluation within a multidisciplinary team, including an experienced thoracic surgeon; 2) Multiple ipsilateral mediastinal lymph nodes metastasized into large masses or multistation metastases (IIIA: T1-2N2 or IIIB: T3-4N2); 3) Contralateral hilar or mediastinal lymph nodes, or ipsilateral or contralateral scalene or supraclavicular lymph nodes metastasis (IIIB: T1-2N3; IIIC: T3-4N3); 4) The lesion invaded the heart, aorta, or esophagus (IIIA: T4N0-1).
5. EGFR mutation or ALK mutation was negative;
6. Patients with at least one evaluable or measurable lesions as per RECIST version 1.1;
7. Patients were newly diagnosed with non-small cell lung cancer, without radiotherapy, chemotherapy, surgery or molecule-targeted treatment.
8. Patients must have enough cardiopulmonary function for the expected pulmonary resections for lung cancer.
9. The main organ function meets the following criteria:1) Blood routine:a. ANC ≥ 1.5×109/L; b. PLT ≥ 100×109/L; c. HB ≥ 90 g/L; 2) Blood biochemistry:TBIL ≤ 1.5×ULN;ALT、AST≤ 2.5×ULN;sCr≤1.5×ULN; 3) Blood coagulation: INR≤1.5×ULN and APTT≤1.5×ULN，endogenous creatinine clearance rate≥45ml/min(Cockcroft-Gault formula);
10. Pregnancy test (serum or urine) has to be performed for woman of childbearing age within 7 days before enrolment and the test result must be negative. They shall take appropriate methods for contraception during the study until the 3 months post the last administration of study drug. For men, (previous surgical sterilization accepted), shall agree to take appropriate methods of contraception during the study until the 3 months post the last administration of study drug;
11. Patient has to voluntarily join the study and sign the Informed Consent Form for the study.

Exclusion Criteria:

1. Patients with autoimmune disease, or a history of autoimmune disease within 2 years prior to the first use of the study drug including but not limited to the following: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, myocarditis, nephritis, hyperthyroidism, hypothyroidism which can be included after hormone replacement therapy; Subjects with childhood asthma have been completely alleviated and without any intervention or vitiligo in adulthood can be included;
2. Subjects with congenital or acquired immunodeficiency such as HIV infection, active hepatitis B (HBV DNA ≥ 2000 IU/mL), hepatitis C (hepatitis C antibody is positive);
3. Subjects with a condition requiring other immunosuppressive medications before 7 days of study drug administration firstly, not including inhaled corticosteroids or physiological doses of systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents);
4. Has received a live vaccine within 4 weeks of planned start of study therapy;
5. Other malignancies have been diagnosed within 5 years prior to the first use of the study drug (excluding skin basal cell carcinoma that has been cured, skin squamous cell carcinoma, and / or carcinoma in situ that has undergone radical resection);
6. Patients with a current or history of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiologic pneumonia, drug-induced pneumonia and severe impairment of lung function;
7. Patients with serious or uncontrollable systemic diseases, such as:

   Patients with hypertension that is difficult to control (systolic blood pressure ≥140 mmHg and diastolic blood pressure ≥90 mmHg); Patients with myocardial ischemia and myocardial infarction above class II (including QT interval prolongation, for man ≥ 450 ms, for woman ≥ 470 ms);
8. Severe infection within 4 weeks before the first administration (such as intravenous drip of antibiotics, antifungal drugs or antiviral drugs), or fever of unknown origin (\> 38.5 ℃) within 4 weeks before the first administration;
9. Allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation;
10. Pregnant or nursing women;
11. Patients with a history of hypersensitivity to any of the study drugs, similar drugs, or excipients;
12. Participated in other clinical trials within 4 weeks;
13. Patients has received the following therapies: anti-PD-1, anti-PD-L1, or anti-PD-L2 drugs or drugs that target another stimulator or synergistically inhibit T cell receptors (e.g., CTLA-4, OX-40, CD137);
14. The investigator believes that there are any conditions that may damage the subject or result in the subject being unable to meet or perform the research request.

Primary outcomes:
measure: R0 Resection Rate
timeFrame: 1 month after surgery
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Pre-operation
measure: Resectability Rate
timeFrame: Pre-operation
measure: Major Pathological Response (MPR) Rate
timeFrame: 1 month after surgery
measure: Rate of grade 3 and higher grade treatment-related adverse events
timeFrame: From date of treatment allocation until surgery or within 30 days after last dose of preoperative treatment
measure: Progression-Free Survival (PFS)
timeFrame: Up to 12 months
Other outcomes:
measure: Pathological Complete Response (pCR) Rate
timeFrame: 1 month after surgery
Locations:
city: Qingdao
country: China
facility: the Affiliated Hospital of Qingdao University
state: Shandong
Study officials:
affiliation: The Affiliated Hospital of Qingdao University
name: Wenjie Jiao, PhD
role: PRINCIPAL_INVESTIGATOR
References: