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

NCT06749886 | Recruiting Phase 2

• 1 other identifier: 2024LY0208
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

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. 1.Overall survival (OS) assessed by investigators according to RECIST 1.1;
2. 2.Objective response rate (ORR) assessed by investigators according to RECIST 1.1;
3. 3.Disease control rate (DCR) assessed by investigators according to RECIST 1.1;
4. 4.Duration of response (DOR) assessed by investigators according to RECIST 1.1;

Conditions

Lung Cancer

Outcome Measures

Primary Outcomes (1)

• progress free survival

  Progression-free survival refers to the time from the start of combined treatment to any objectively documented tumor progression or patient death (the last follow-up date for patients lost to follow-up; the end of follow-up date for patients still alive at the end of the study).

  up to 24 months

Secondary Outcomes (4)

• overall survival

  up to 24 months

• objective response rate

  12 months

• Disease control rate

  12 months

• Duration of remission

  12 months

Study Arms (1)

cohort1

EXPERIMENTAL

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

Drug: Denosumab; Drug: tislelizumab; Drug: Docetaxel

Interventions

Denosumab 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

cohort1

tislelizumab DRUG

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

cohort1

Docetaxel DRUG

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

cohort1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age≥ 18 years old;
• Patients with histologically or cytologically confirmed non-bone metastases stage IV NSCLC;
• 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);
• first-line treatment with immune checkpoint inhibitors and clinical benefit (PFS ≥ 3 months);
• 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);
• ECOG PS: 0-2 points;
• Estimated survival time≥ 3 months;
• 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);
• 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;
• adequate renal function, defined as creatinine clearance ≥50ml/min (Cockcroft-Gault formula);
• Adequate coagulation function, defined as the international normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 times ULN;
• 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;
• 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);
• 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.

You may not qualify if:

• Patients on first-line docetaxel chemotherapy;
• 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);
• 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);
• 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);
• 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;
• Active hemoptysis, active diverticulitis, intra-abdominal abscess, gastrointestinal obstruction and peritoneal metastasis requiring clinical intervention;
• Received solid organ or blood system transplantation;
• Class III-IV congestive heart failure (New York Heart Association classification), poorly controlled and clinically significant arrhythmia;
• 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;
• 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);
• History of non-infectious pneumonitis requiring corticosteroid treatment within 1 year before the first dose;
• Have an active infection requiring treatment or have used systemic anti-infective drugs within one week before the first dose;
• Known psychiatric illness or substance abuse that may affect compliance with trial requirements;

Sponsors & Collaborators

• Shanghai Pulmonary Hospital, Shanghai, China: lead

Study Sites (1)

Shanghai Pulmonary Hospital

Shanghai, 200433, China

RECRUITING

MeSH Terms

Conditions

Lung Neoplasms

Interventions

Denosumab; tislelizumab; Docetaxel

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Central Study Contacts

Chunxia Su

CONTACT

13601899076; susu_mail@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of the Clinical Research Center

Study Record Dates

• First Submitted: December 12, 2024
• First Posted: December 27, 2024
• Study Start: November 19, 2024
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): June 30, 2027
• Last Updated: December 27, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)