Preoperative Neoadjuvant Immunotherapy Combined With Chemotherapy for Stage Ⅲ Unresectable Non-small Cell Lung Cancer (PILOT)

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

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

Study Overview

• Status: Recruiting
• Conditions: Non-small-cell Lung Cancer (NSCLC)
• Intervention / Treatment: Drug: Tislelizumab; Drug: Pemetrexed (Non-squamous NSCLC) or Nab-paclitaxel(Squamous NSCLC); Drug: Carboplatin or Cisplatin; Procedure: Surgery

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.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Shandong
    • Qingdao, Shandong, China, 266000
      • Recruiting
      • The Affiliated Hospital of Qingdao University
      • Contact: Zhe Wu, PhD; Phone Number: +86 17863934867; Email: 17863934867@163.com

Participation Criteria

Eligibility Criteria

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

Description

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.

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: Experimental Group; Participants receive 2-4 cycles of Tislelizumab combined with chemotherapy treatment during preoperative period, every 3 weeks for 4 cycles at most.

Drug: Tislelizumab; Tislelizumab: 200mg, ivgtt, day 1 of each 21-day cycle, neoadjuvant therapy : 2-4 cycles; Adjuvant therapy: 16cycles at most.; Other Names: PD-1 antibody; Drug: Pemetrexed (Non-squamous NSCLC) or Nab-paclitaxel(Squamous NSCLC); Pemetrexed: 500 mg/m^2, ivgtt, day 1 of each 21-day cycle, 2-4 cycles. Nab-paclitaxel: 260mg/m^2, ivgtt, day 1 of each 21-day cycle, 2-4 cycles.; Other Names: chemotherapeutic drug; Drug: Carboplatin or Cisplatin; Carboplatin was given dosed to an area under the serum concentration-time curve (AUC) of 5 ivgtt on day 1 of each 21-day cycle for 2-4 cycles. Cisplatin: 75 mg/m^2, ivgtt, day 1 of each 21-day cycle, 2-4 cycles.; Other Names: chemotherapeutic drug; Procedure: Surgery; Surgery must be done within the 4th-6th week from day 1 the last cycle of neoadjuvant treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
R0 Resection Rate	R0 Resection Rate: The pathological results will showed that the incision margin was negative and no residual cancer cells were found under the microscope.	1 month after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Objective Response Rate (ORR): defined as the proportion of patients whose tumor size shrinks to predefined values，which including cases of CR and PR. Objective tumor response will be assessed using RECIST 1.1. Subjects must have measurable tumor lesions at baseline, and the response evaluation criteria are classified as complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) according to RECIST 1.1.	Pre-operation
Resectability Rate	Resectability Rate is defined as the percentage of patients who were able to undergo surgery after neoadjuvant therapy.	Pre-operation
Major Pathological Response (MPR) Rate	Major Pathological Response (MPR) Rate: defined as ≤ 10% of residual tumor cells in the surgically resected tumor specimen and sampled regional lymph nodes after neoadjuvant treatment.	1 month after surgery
Rate of grade 3 and higher grade treatment-related adverse events	Adverse events will be evaluated and recorded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0).	From date of treatment allocation until surgery or within 30 days after last dose of preoperative treatment
Progression-Free Survival (PFS)	Progression-Free Survival (PFS): defined as the time from the first dose until the date of first documented progression or date of death from any cause, whichever came first.	Up to 12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological Complete Response (pCR) Rate	Pathological Complete Response (pCR) Rate: no residual tumor cells in the surgically resected tumor specimen and all sampled regional lymph nodes after neoadjuvant treatment.	1 month after surgery

Collaborators and Investigators

• Sponsor: The Affiliated Hospital of Qingdao University
• Investigators: Principal Investigator: Wenjie Jiao, PhD, The Affiliated Hospital of Qingdao University

Study record dates

Study Major Dates

• Study Start (Actual): January 18, 2024
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: March 28, 2024
• First Submitted That Met QC Criteria: April 7, 2024
• First Posted (Actual): April 10, 2024

Study Record Updates

• Last Update Posted (Actual): April 10, 2024
• Last Update Submitted That Met QC Criteria: April 7, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Immunotherapy; Chemotherapy; Non-small-cell Lung Cancer (NSCLC)
• 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; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Folic Acid Antagonists; Carboplatin; Paclitaxel; Pemetrexed; Tislelizumab
• Other Study ID Numbers: QYFYEC2023-95

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