Tislelizumab Combined With Recombinant Human Endostatin Combined With Chemotherapy for Unresectable Stage III Non-small Cell Lung Cancer.

NCT ID: NCT06617936

Last Updated: 2025-07-15

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-08-27
• Study Completion Date: 2027-09-10

Brief Summary

This is a prospective, single-arm, multicenter, phase II clinical study designed to evaluate the initial efficacy and safety of patients receiving Tislelizumab in combination with recombinant human endostatin injection plus chemotherapy for stage III unresectable non-small cell lung cancer. To evaluate the surgical conversion rate of tirellizumab combined with recombinant human endostatin injection and chemotherapy induction therapy in patients with initially unresectable stage III non-small cell lung cancer.

Conditions

Unresectable Non-small Cell Lung Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Participant Group/Arm A

Participants receive 2-4 cycles of Tislelizumab With Recombinant human endostatin combined with Chemotherapy treatment during preoperative period, every 3 weeks once for 4 cycles at most.

After neoadjuvant therapy, Patients evaluated for MDT who can be surgically resected will be placed in the surgical group for surgical excision.

Surgery will be performed within 4 to 6 weeks after completion of preoperative therapy.

After surgery, participants will receive adjuvant therapy with tislelizumab combined with recombinant human endostatin injection every 3 weeks until disease progression or postoperative adjuvant therapy for 1 year.

Group Type: EXPERIMENTAL

neoadjuvant therapy:Tislelizumab With Recombinant human endostatin combined with Chemotherapy

Intervention Type: DRUG

neoadjuvant therapy : Tislelizumab: 200mg, ivgtt, day 1 ; Recombinant Human Endostatin Injection (Endostar),210mg was pumped intravenously for 3 consecutive days; Pemetrexed (Non-squamous NSCLC) or Nab-paclitaxel(Squamous NSCLC):Pemetrexed: 500 mg/m\^2, ivgtt, day 1. Nab-paclitaxel: 260mg/m\^2, ivgtt, day 1.; Carboplatin:Carboplatin was given dosed to an area under the serum concentration-time curve (AUC) of 5 ivgtt on day 1 ; every 21 days for 1 cycle,2-4 cycles; (If the preoperative neoadjuvant did not reach 4 cycles, the treatment with ralizumab combined with recombinant human endostatin injection and chemotherapy for 1-2 cycles can be continued after surgery, and the total cycle of chemotherapy before and after surgery is up to 4 cycles)

surgery

Intervention Type: PROCEDURE

Patients who are discussed by the MDT panel to evaluate surgical resection will undergo surgery.Surgery must be done within the 4th-6th week from day 1 the last cycle of neoadjuvant treatment.

Adjuvant therapy:Tislelizumab and Recombinant Human Endostatin Injection (Endostar)

Intervention Type: DRUG

Adjuvant therapy Tislelizumab: 200mg, ivgtt, day 1 of each 21-day cycle, 17 cycles at most. Recombinant Human Endostatin Injection (Endostar):210mg was pumped intravenously for 3 consecutive days, every 21 days for 1 cycle,17 cycles at most.

Participant Group/Arm B

Participants receive 2-4 cycles of Tislelizumab With Recombinant human endostatin combined with Chemotherapy treatment , every 3 weeks once for 4 cycles at most. After neoadjuvant therapy, Patients evaluated by MDT as unresectable will be placed in the standard treatment group, where the investigator will select the standard treatment regimen determined by the MDT discussion.

Group Type: EXPERIMENTAL

neoadjuvant therapy:Tislelizumab With Recombinant human endostatin combined with Chemotherapy

Intervention Type: DRUG

neoadjuvant therapy : Tislelizumab: 200mg, ivgtt, day 1 ; Recombinant Human Endostatin Injection (Endostar),210mg was pumped intravenously for 3 consecutive days; Pemetrexed (Non-squamous NSCLC) or Nab-paclitaxel(Squamous NSCLC):Pemetrexed: 500 mg/m\^2, ivgtt, day 1. Nab-paclitaxel: 260mg/m\^2, ivgtt, day 1.; Carboplatin:Carboplatin was given dosed to an area under the serum concentration-time curve (AUC) of 5 ivgtt on day 1 ; every 21 days for 1 cycle,2-4 cycles; (If the preoperative neoadjuvant did not reach 4 cycles, the treatment with ralizumab combined with recombinant human endostatin injection and chemotherapy for 1-2 cycles can be continued after surgery, and the total cycle of chemotherapy before and after surgery is up to 4 cycles)

Standard Treatment

Intervention Type: OTHER

Patients assessed by the MDT panel as inoperable for surgical treatment will be selected by the investigator for a standard treatment protocol determined by the MDT discussion

Interventions

neoadjuvant therapy:Tislelizumab With Recombinant human endostatin combined with Chemotherapy

neoadjuvant therapy : Tislelizumab: 200mg, ivgtt, day 1 ; Recombinant Human Endostatin Injection (Endostar),210mg was pumped intravenously for 3 consecutive days; Pemetrexed (Non-squamous NSCLC) or Nab-paclitaxel(Squamous NSCLC):Pemetrexed: 500 mg/m\^2, ivgtt, day 1. Nab-paclitaxel: 260mg/m\^2, ivgtt, day 1.; Carboplatin:Carboplatin was given dosed to an area under the serum concentration-time curve (AUC) of 5 ivgtt on day 1 ; every 21 days for 1 cycle,2-4 cycles; (If the preoperative neoadjuvant did not reach 4 cycles, the treatment with ralizumab combined with recombinant human endostatin injection and chemotherapy for 1-2 cycles can be continued after surgery, and the total cycle of chemotherapy before and after surgery is up to 4 cycles)

Intervention Type: DRUG

surgery

Patients who are discussed by the MDT panel to evaluate surgical resection will undergo surgery.Surgery must be done within the 4th-6th week from day 1 the last cycle of neoadjuvant treatment.

Intervention Type: PROCEDURE

Adjuvant therapy:Tislelizumab and Recombinant Human Endostatin Injection (Endostar)

Adjuvant therapy Tislelizumab: 200mg, ivgtt, day 1 of each 21-day cycle, 17 cycles at most. Recombinant Human Endostatin Injection (Endostar):210mg was pumped intravenously for 3 consecutive days, every 21 days for 1 cycle,17 cycles at most.

Intervention Type: DRUG

Standard Treatment

Patients assessed by the MDT panel as inoperable for surgical treatment will be selected by the investigator for a standard treatment protocol determined by the MDT discussion

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

7. Good organ function;

• Patients have not received blood transfusion or growth factor support therapy ≤ 14 days prior to sample collection during the screening period and: Absolute neutral cell count (ANC) ≥1.5 x 109/L
• Platelet ≥100 x 109/L
• Hemoglobin ≥90 g/L

• Calculated creatinine clearance (CrCl) (Cockcroft-Gault formula)
• Patients scheduled to receive cisplatin: creatinine clearance ≥ 60 mL/min
• Patients scheduled to receive carboplatin: creatinine clearance ≥ 45 mL/min

• Serum total bilirubin ≤1.5 × upper limit of normal (ULN) (patients with Gilbert's syndrome must have total bilirubin < 3 × ULN)
• AST and ALT≤ 2.5 x ULN
• Patients who did not receive anticoagulant therapy: International standardized ratio or activated partial thromboplastin time ≤ 1.5 × ULN
• Albumin ≥25 g/L (2.5 g/dL).

8. Willing and able to comply with study plan visits, treatment plans, laboratory tests and other study procedures;

9. The total amount of lung function, as assessed by the surgeon, is sufficient to withstand the proposed pneumonectomy;

10. Women of childbearing age must take a serum pregnancy test within 3 days before the first medication, and the result is negative. Female subjects of reproductive age and male subjects whose partners are women of reproductive age must agree to use highly effective methods of contraception during the study period and for 120 days after the last dose of the study drug

Exclusion Criteria

1. Patients with known EGFR gene mutation, ALK rearrangement, ROS-1 fusion, RET fusion, HER-2 mutation, MET mutation, and non-squamous cell carcinoma with unknown driver gene status;

2. Previous treatment for current lung cancer, including radiotherapy and all systemic antitumor agents, including chemotherapy, immunotherapy, targeted therapy or antiangiogenic therapy.

3. Patients with large cell neuroendocrine carcinoma (LCNEC) components and non-small cell lung cancer with mixed small cell components.

4. Patients received other approved systemic immunomodulators (including, but not limited to, interferon, interleukin 2, tumor necrosis factor, thymus pentapeptide, and thymofasin) within 4 weeks prior to initial administration.

5. In the course of treatment, researchers determined that patients' tumors were more likely to invade important blood vessels and cause fatal bleeding.

6. Clinically significant hemoptysis (more than 50ml of hemoptysis per day), or clinically significant bleeding symptoms or significant bleeding tendency (such as gastrointestinal bleeding, gastric ulcer bleeding, gastrointestinal bleeding, hemorrhagic gastric ulcer, fecal occulted blood ++ or above baseline, or vasculitis) within 3 months before the study.

7. Any Chinese herbs used for cancer control were used within 14 days prior to the first administration of the study drug.

8. Have received live vaccine within 30 days before the first dose. Including but not limited to the following: mumps, rubella, measles, varicella/shingles (chickenpox), yellow fever, rabies, BCG and typhoid vaccine (inactivated virus vaccine allowed); Live or attenuated vaccine is expected to be required during the study period or within 5 months after the last dose.

9. For any condition requiring systemic treatment with corticosteroids (prednisone or equivalent >10 mg/ day) or other immunosuppressive agents within 14 days prior to the first administration of the study drug, the investigator assessed the patient as having an impact on the study treatment.

10. Active autoimmune diseases requiring systemic treatment in patients assessed by the investigator as having an impact on investigational treatment.

11. Patients with interstitial lung disease, non-infectious pneumonia, or other diseases that are not under control, including diabetes, pulmonary fibrosis, acute lung disease, etc., that the investigators have assessed as having an impact on the study treatment.

12. Patients with a history of major diseases or clinical manifestations that may affect the function of organ systems and are assessed by the investigator as having implications for the study and treatment.

13. Study severe chronic or active infections (including tuberculosis) requiring systemic antimicrobial, antifungal, or antiviral treatment ≤14 days before the first administration of the drug.

14. Uncontrolled active hepatitis B (defined as positive HBV surface antigen [HBsAg] test results during screening and HBV-DNA test values higher than the upper limit of normal values in the laboratory of the research center; (Participants with HBV-DNA levels < 500 IU/mL within 28 days prior to enrollment, who have received local standard antiviral therapy for at least 14 days and who are willing to continue antiviral therapy during the study period may be enrolled); Subjects with active hepatitis C (defined as positive HCV surface antibody [HCsAb] test results during screening, positive HCV-RNA);

15. Known human immunodeficiency virus (HIV) infection (known HIV antibody positive);

16. Grade III-IV congestive heart failure (New York Heart Association classification), poorly controlled and clinically significant arrhythmias;

17. Any arterial thrombosis, embolism, or ischemia, such as myocardial infarction, unstable angina pectoris, cerebrovascular accident, or transient ischemic attack, occurred within 6 months prior to treatment;

18. Concurrent participation in another therapeutic clinical study, unless it is an observational (non-interventional) clinical study or in the follow-up period of an interventional study.

19. Medical history or evidence of disease that may interfere with the test results, prevent participants from participating fully in the study, abnormal treatment or laboratory test values, or other conditions that the investigator considers unsuitable for enrollment. The Investigator considers that there are other potential risks that are not suitable for participation in the study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hua Zhang

OTHER_GOV

Sponsor Role: lead

Responsible Party

Hua Zhang

Head of thoracic surgery

Responsibility Role: SPONSOR_INVESTIGATOR

Locations

Shandong Public Health Clinical Center (ShandongPHCC)

Jinan, Shandong, China

Site Status: RECRUITING

Countries

China

Central Contacts

Hua Zhang, PhD

Role: CONTACT

zhanghua_science@163.com

0531-83347512

Facility Contacts

Hua Zhang, doctor

Role: primary

zhanghua_science@163.com

0531-83347512

Other Identifiers

GWLCZXEC2024-55-2

Identifier Type: -

Identifier Source: org_study_id