An Exploratory Study of Tislelizumab in Combination with Chemotherapy in Immuno-experienced Patients with EGFR/ALK/ROS1-negative Advanced NSCLC in the Second-line Setting

NCT ID: NCT06749886

Last Updated: 2024-12-27

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-11-19
• Study Completion Date: 2027-06-30

Brief Summary

The goal of this clinical trial is to explore the efficacy and safety of denosumab in combination with tislelizumab and chemotherapy in the second-line treatment of immuno-experienced patients with EGFR/ALK/ROS1-negative advanced NSCLC.

Primary endpoint:

progression-free survival (PFS) assessed by investigators according to RECIST 1.1;

Secondary endpoint:

1. Overall survival (OS) assessed by investigators according to RECIST 1.1;

2. Objective response rate (ORR) assessed by investigators according to RECIST 1.1;

3. Disease control rate (DCR) assessed by investigators according to RECIST 1.1;

4. Duration of response (DOR) assessed by investigators according to RECIST 1.1;

Exploratory endpoint:

bone metastasis-free survival.

Participants will receive denosumab combined with tislelizumab and docetaxel.

Conditions

Lung Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

cohort1

The subjects in this cohort will receive denosumab combined with tislelizumab and docetaxel.

Group Type: EXPERIMENTAL

Denosumab

Intervention Type: DRUG

Denosumab, 120 mg subcutaneous injection, every 21-28 days a cycle, given on the first day, a loading dose is given on d8 of the first cycle, and continued use

tislelizumab

Intervention Type: DRUG

Tislelizumab, 200 mg intravenous infusion, every 21 days a cycle, given on the first day, and continued use

Docetaxel

Intervention Type: DRUG

Docetaxel, 60 mg/m2 intravenous infusion, every 21 days a cycle, given on the first day, and continued use.

Interventions

Denosumab

Denosumab, 120 mg subcutaneous injection, every 21-28 days a cycle, given on the first day, a loading dose is given on d8 of the first cycle, and continued use

Intervention Type: DRUG

tislelizumab

Tislelizumab, 200 mg intravenous infusion, every 21 days a cycle, given on the first day, and continued use

Intervention Type: DRUG

Docetaxel

Docetaxel, 60 mg/m2 intravenous infusion, every 21 days a cycle, given on the first day, and continued use.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Age≥ 18 years old;

2. Patients with histologically or cytologically confirmed non-bone metastases stage IV NSCLC;

3. EGFR, ALK, and ROS1 are all wild-type (for other driver genes, if there is no first-line approval for corresponding targeted therapy or if the patient refuses targeted therapy, these patients are allowed to be enrolled);

4. first-line treatment with immune checkpoint inhibitors and clinical benefit (PFS ≥ 3 months);

5. Have measurable lesions (according to RECIST 1.1 criteria, the long diameter of CT scan of tumor lesions is ≥10mm, the short diameter of CT scan of lymph node lesions is ≥15mm, and the thickness of the scanning layer is not more than 5mm, and the measurable lesions have not received local treatment such as radiotherapy and cryotherapy);

6. ECOG PS: 0-2 points;

7. Estimated survival time≥ 3 months;

8. Adequate hematologic function, defined as absolute neutrophil count ≥1.5×109/L, platelet count ≥ 80×109/L, hemoglobin ≥ 90g/L (no history of blood transfusion within 7 days, not corrected with G-CSF and other hematopoietic stimulating factors);

9. adequate liver function, defined as total bilirubin levels ≤1.5 times the upper limit of normal (ULN) and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels ≤ 2.5 times ULN, or for patients with liver metastases, AST and ALT levels ≤ 5 times ULN;

10. adequate renal function, defined as creatinine clearance ≥50ml/min (Cockcroft-Gault formula);

11. Adequate coagulation function, defined as the international normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 times ULN;

12. For female subjects of childbearing age, a negative urine or serum pregnancy test should be performed within 3 days prior to receiving the first dose of study drug, and if the urine pregnancy test result cannot be confirmed as negative, a blood pregnancy test is required;

13. If there is a risk of conception, male and female patients need to use highly effective contraception (i.e., a method with a failure rate of less than 1% per year) and continue until at least 180 days after stopping the trial treatment (Note: abstinence can be accepted as a contraceptive method if abstinence is the subject's usual lifestyle and preferred contraceptive method);

14. Subjects voluntarily joined this study, signed a written informed consent form before the implementation of any trial-related procedures, had good compliance, and cooperated with follow-up.

Exclusion Criteria

1. Patients on first-line docetaxel chemotherapy;

2. Patients with symptomatic brain metastases (symptoms of brain metastases remain clinically stable for at least 1 month after treatment, and no steroids and anticonvulsants can be enrolled for at least 1 month before entering the study);

3. Presence of clinically uncontrollable pleural effusion/ascites effusion (patients who do not need to drain the effusion or who have stopped draining for 3 days without a significant increase in effusion can be enrolled);

4. have not recovered adequately from toxicity and/or complications caused by any intervention (i.e., ≤ grade 1 or to baseline, excluding fatigue or alopecia, prior to initiation of treatment);

5. Diagnosis of other malignant tumors within 5 years before the first dose, excluding radically treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin and/or carcinoma in situ that has undergone radical resection, if other malignant tumors or lung cancer are diagnosed more than 5 years before administration, pathological or cytological diagnosis of recurrent metastatic lesions is required;

6. Active hemoptysis, active diverticulitis, intra-abdominal abscess, gastrointestinal obstruction and peritoneal metastasis requiring clinical intervention;

7. Received solid organ or blood system transplantation;

8. Class III-IV congestive heart failure (New York Heart Association classification), poorly controlled and clinically significant arrhythmia;

9. Active autoimmune disease requiring systemic treatment (such as the use of disease-modifying drugs, corticosteroids, or immunosuppressants) within 2 years prior to the first dose. Replacement therapies (e.g., thyroxine, insulin, or physiologic corticosteroids for adrenal or pituitary insufficiency) are not considered systemic therapy;

10. Patients who need long-term systemic use of corticosteroids (patients who need intermittent use of bronchodilators, inhaled corticosteroids, or local corticosteroids due to COPD and asthma can be enrolled);

11. History of non-infectious pneumonitis requiring corticosteroid treatment within 1 year before the first dose;

12. Have an active infection requiring treatment or have used systemic anti-infective drugs within one week before the first dose;

13. Known psychiatric illness or substance abuse that may affect compliance with trial requirements;

14. Those who are considered unsuitable for inclusion by the investigator.

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

Sponsors

Shanghai Pulmonary Hospital, Shanghai, China

OTHER

Sponsor Role: lead

Responsible Party

Chunxia Su

Director of the Clinical Research Center

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Shanghai Pulmonary Hospital

Shanghai, , China

Site Status: RECRUITING

Countries

China

Central Contacts

Chunxia Su

Role: CONTACT

Phone: 13601899076

Email: susu_mail@126.com

Facility Contacts

Chunxia Su

Role: primary

Chunxia Su, doctor

Role: backup

Other Identifiers

2024LY0208

Identifier Type: -

Identifier Source: org_study_id