Predictive Biomarker for Efficacy and Safety of Combination of Chemotherapy and Tislelizumab in NSCLC

NCT05244837 | Unknown Phase 2

• 1 other identifier: A2020-008
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 4

Brief Summary

To explore the related biomarkers for safety and efficacy of the combination of chemotherapy and tislelizumab in non-small cell lung cancer

Conditions

Tislelizumab; Safety; Biomarker; Chemotherapy

Outcome Measures

Primary Outcomes (1)

• Drug safety incidents

  Safety as measured by number of participants with Grade 3 and 4 lab abnormalities, as defined by CTCAE v5.0

  90 days after initial treatment of tislelizumab or 30 days post-operation, whichever is later

Secondary Outcomes (4)

• Evaluation of the major pathologic response (MPR)

  From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first,assessed up to 36 months

• pathologic complete response

  From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first，assessed up to 36 months

• Resectable rate

  From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first，assessed up to 36 months

• Disease-free survival

  From date of randomization until the date of first documented recurrence or date of death from any cause, whichever came first, assessed up to 60months

Other Outcomes (1)

• PD-L1 expression, TMB, and other potential predictive biomarkers, correlated with response to treatment

  36 months

Study Arms (2)

Arm A:Resectable Stage IIB-IIIA Non Small Cell Lung Cancer (NSCLC)

EXPERIMENTAL

Patients received neoadjuvant treatment with Platinum-based doublet chemotherapy plus tislelizumab(200 mg) on day 1 of each 21-day cycle, for 3-4 cycles before surgical resection, followed by adjuvant intravenous tislelizumab monotherapy for 1 year ( 200 mg every 3 weeks for 2 cycles, followed by 200 mg every 4 weeks for 12 cycles).

Drug: Tislelizumab 200 mg; Drug: Carboplatin AUC 5; Drug: pemetrexed 500mg/m2; Drug: Paclitaxel 175mg/m2; Drug: Nab-paclitaxel 260 mg/m2

Arm B：Unresectable Stage IIIA/IIIB/IIIC or IV Non Small Cell Lung Cancer (NSCLC)

EXPERIMENTAL

Patients received neoadjuvant treatment with Platinum-based doublet chemotherapy plus tislelizumab(200 mg) on day 1 of each 21-day cycle, for 4-6 cycles , followed by adjuvant intravenous tislelizumab monotherapy ( 200 mg every 3 weeks )，until disease progression or intolerable toxicity If surgery is not possible；If surgery is possible after assessment, subsequent treatment at the discretion of the investigator

Drug: Tislelizumab 200 mg; Drug: Carboplatin AUC 5; Drug: pemetrexed 500mg/m2; Drug: Paclitaxel 175mg/m2; Drug: Nab-paclitaxel 260 mg/m2

Interventions

Tislelizumab 200 mg DRUG

Tislelizumab 200mg IV Q3W + Followed by adjuvant treatment for 1 year (Tislelizumab 200 mg IV Q3W for 2 cycles and Tislelizumab 200 mg Q4W for 12 cycles)

Also known as: Tislelizumab

Arm A:Resectable Stage IIB-IIIA Non Small Cell Lung Cancer (NSCLC); Arm B：Unresectable Stage IIIA/IIIB/IIIC or IV Non Small Cell Lung Cancer (NSCLC)

Carboplatin AUC 5 DRUG

Carboplatin AUC 5 IV Q3W

Also known as: Carboplatin

Arm A:Resectable Stage IIB-IIIA Non Small Cell Lung Cancer (NSCLC); Arm B：Unresectable Stage IIIA/IIIB/IIIC or IV Non Small Cell Lung Cancer (NSCLC)

pemetrexed 500mg/m2 DRUG

Pemetrexed 500mg/m2 IV Q3W if non-squamous lung cancer

Also known as: pemetrexed

Arm A:Resectable Stage IIB-IIIA Non Small Cell Lung Cancer (NSCLC); Arm B：Unresectable Stage IIIA/IIIB/IIIC or IV Non Small Cell Lung Cancer (NSCLC)

Paclitaxel 175mg/m2 DRUG

Paclitaxel 175mg/m2 IV Q3W if squamous lung cancer

Also known as: Paclitaxel

Arm A:Resectable Stage IIB-IIIA Non Small Cell Lung Cancer (NSCLC); Arm B：Unresectable Stage IIIA/IIIB/IIIC or IV Non Small Cell Lung Cancer (NSCLC)

Nab-paclitaxel 260 mg/m2 DRUG

nab-paclitaxel 260 mg/m2 Q3W if squamous lung cancer

Also known as: Nab-paclitaxel

Arm A:Resectable Stage IIB-IIIA Non Small Cell Lung Cancer (NSCLC); Arm B：Unresectable Stage IIIA/IIIB/IIIC or IV Non Small Cell Lung Cancer (NSCLC)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to provide written informed consent and able to understand and agree to comply with study requirements and evaluation forms;
• Must be at least 18 years of age (or the legal age of commitment in the study occurrence jurisdiction) on the date the informed consent is signed;
• At least 1 measurable lesion as defined by RECIST v1.1 criteria; Note: Target lesions must be selected to meet one of the following criteria: 1) no prior local therapy or 2) subsequent progression within the previously treated local treatment area as determined by RECIST v1.1.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1;
• Eligible for platinum-based doublet chemotherapy;
• pre-treatment tumor tissue samples for biomarker analysis can be provided;
• Adequate hematology and end-organ function as defined by the following laboratory values (≤ 7 days prior to first dose):
• Patients did not require blood transfusion, platelet transfusion, or growth factor support ≤ 14 days prior to blood draw: i. Absolute neutrophil count ≥ 1.5 \* 109/L ii. Platelets ≥ 100 \* 109/L iii. Hemoglobin ≥ 90 g/L
• Serum creatinine ≤ 1.5 × upper limit of normal (ULN), or glomerular filtration rate ≥ 60 mL/min calculated by CKD-EPI formula;
• AST and ALT ≤ 2.5 times ULN, or AST and ALT ≤ 5 times ULN in patients with a documented history of liver metastases;
• Serum total bilirubin ≤ 1.5 times ULN (total bilirubin must be \< 3 times ULN for patients with Gilbert's syndrome)
• International normalized ratio (INR) ≤ 1.5 or prothrombin time ≤ 1.5 times ULN;
• Partial thromboplastin time (APTT) ≤ 1.5 × ULN;
• Females of childbearing potential must agree to practice highly effective contraception for the duration of the study and for ≥ 120 days after dosing and have a negative serum pregnancy test ≤ 7 days before the first dose of study drug;
• Nonsterilized men must agree to use highly effective contraception for the duration of the study and for ≥ 120 days after study drug administration;

You may not qualify if:

• Patients with EGFR mutation, ALK gene rearrangement or ROS1 gene rearrangement:
• For patients with non-squamous cell carcinoma, if EGFR mutation status is unknown, tissue samples should be provided for local or central laboratory testing before enrollment;
• For patients with squamous cell carcinoma, if EGFR mutation status is unknown, it is not required to conduct test at screening;
• Testing at screening is not required if ALK gene rearrangement or ROS1 gene rearrangement status is unknown;
• Allergic to any study drug or excipients;
• Patients who have been treated with immune checkpoint inhibitors such as anti-PD-1, PD-L1 or CTLA-4 therapy;
• Cohort A: patients who have received systemic platinum-based doublet chemotherapy; Cohort B: patients who have received systemic platinum-based doublet chemotherapy as advanced systemic therapy;
• Patients received other approved systemic anticancer therapy or systemic immunomodulators (including but not limited to interferon, interleukin 2, and tumor necrosis factor) 4 weeks before the first dose;
• Cohort B: patients with refractory pleural effusion or ascites, such as pleural effusion or ascites requiring puncture and drainage 2 before the first dose;
• Cohort B: Patients with active leptomeningeal disease or brain metastasis, such as central nervous system symptoms, requiring interventional therapy (including but not limited to radiotherapy, intracranial pressure lowering therapy, etc.);
• Patients with any disease requiring systemic treatment with corticosteroids (daily dose of prednisone or equivalent \> 10 mg) or other immunosuppressive drugs 14 days before grouping; Note: epinephrine replacement steroids (daily dose of prednisone ≤ 10 mg or equivalent) are allowed;Inhaled corticosteroids with minimal intranasal or systemic absorption; prophylactic use of prescription corticosteroids (eg, for contrast medium allergy) for short duration (≤ 7 days) or for treatment of non-autoimmune diseases (eg, delayed hypersensitivity reaction to contact allergens) is permitted;
• Active autoimmune disease or history of autoimmune disease that may recur; Note: well-controlled type 1 diabetes is allowed; hypothyroidism (controlled with thyroid hormone replacement only); well-controlled celiac disease; skin disease not requiring systemic treatment (eg, vitiligo, psoriasis, alopecia); any other condition that is not expected to recur in the absence of an external trigger.
• History of interstitial lung disease, pneumonitis or uncontrolled systemic diseases, including diabetes, hypertension, pulmonary fibrosis, acute lung disease;
• \. Serious infection occurred before grouping, including but not limited to hospitalization due to infectious complications, bacteremia or severe pneumonia; severe chronic or active infection (including pulmonary tuberculosis infection, etc.) requiring systemic (oral or intravenous) antibiotics within 14 days before grouping;
• HBV deoxyribonucleic acid (DNA) must be \< 500 IU/mL (or 2500 copies/mL) in inactive/asymptomatic carriers, patients with chronic or active hepatitis B virus (HBV) at screening Note: Patients with detectable hepatitis B surface antigen (HBsAg) or detectable HBV DNA should be treated according to treatment guidelines. Patients receiving antiviral therapy at screening should be treated \> 2 weeks prior to screening.

Sponsors & Collaborators

• Hao Long: lead

Study Sites (4)

Guangzhou Medical University Affiliated Cancer Hospital

Guangzhou, Guangdong, China

ACTIVE NOT RECRUITING

Sun Yat-sen University cancer center

Guangzhou, Guangdong, China

RECRUITING

Jiangmen Central Hospital

Jiangmen, Guangdong, China

RECRUITING

Guangzhou panyu central hospital

Guangzhou, China

ACTIVE NOT RECRUITING

Related Publications (1)

• Cao A, Lin Y, Guan S, Chen Y, Zhai W, Zhou Y, Feng S, Guan Y, Zhang Y, Huang M, Wang X, Long H. Baseline multi-omics signatures could predict therapeutic response to neoadjuvant anti-PD-1 immunochemotherapy in non-small-cell lung cancer. Clin Transl Med. 2026 Jan;16(1):e70579. doi: 10.1002/ctm2.70579.

  PMID: 41499358 DERIVED

MeSH Terms

Interventions

tislelizumab; Carboplatin; Pemetrexed; Paclitaxel; 130-nm albumin-bound paclitaxel

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Central Study Contacts

Long Hao, MD

CONTACT

+86-20-87343314; longhao@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief Physician

Model Details: This study consists includes two groups, one is the treatment of patients with resectable lung cancer and the other is the treatment of patients with unresectable lung cancer.

Study Record Dates

• First Submitted: October 31, 2021
• First Posted: February 17, 2022
• Study Start: December 22, 2020
• Primary Completion: July 1, 2022
• Study Completion: December 1, 2023
• Last Updated: February 17, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (4)