A Study for Identification of Predictive Immune Biomarker for Atezolizumab Therapy in NSCLC Patients

NCT04312308 | Completed

• 1 other identifier: 4-2019-0948
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

The study aimed to elucidate predictive immune related biomarker to the responsiveness to the PD-L1 blockade and evaluate the dynamics of immune cells in peripheral blood from NSCLC patients during atezolizumab treatment.

Conditions

Non Small Cell Lung Cancer

Keywords

Immune biomarker

Outcome Measures

Primary Outcomes (5)

• To explore early biomarker to predict response and overall survival after Atezolizumab therapy

  Analysis of immune marker using FACS

  up to 1year

• To explore early biomarker to predict response and overall survival after Atezolizumab therapy

  Multiplexed biomarker analysis of tumor and immune cells in tumor microenvironment (TME) (Pre-treatment biopsy is mandatory but biopsy is optional for disease progression)

  up to 1year

• To explore early biomarker to predict response and overall survival after Atezolizumab therapy

  microbiome

  up to 1year

• To explore early biomarker to predict response and overall survival after Atezolizumab therapy

  Genetic analysis

  up to 1year

• To explore early biomarker to predict response and overall survival after Atezolizumab therapy

  Single cell RNA sequencing (scRNA-seq)

  up to 1year

Secondary Outcomes (4)

• ORR(Objective response rate)

  Atezolizumab treatment will be given every 3 weeks up to progression or 1 year. The manner and interval of efficacy assessment for tumor scan will depends on the investigator's decision.

• PFS(Progression free survival)

  Atezolizumab treatment will be given every 3 weeks up to progression or 1 year. The manner and interval of efficacy assessment for tumor scan will depends on the investigator's decision.

• OS(Overall survival)

  Overall survival will be followed continuously while subjects are on the study drug and every 6 months after discontinuation or progression for up to 5 years

• Safety

  local laboratory assessments should be done with prior to each atezolizumab dose Atezolizumab treatment will be given every 3 weeks up to progression or 1 year.

Study Arms (1)

Non-Small Cell Lung Cancer Treated with Atezolizumab

Patients with Non-Small Cell Lung Cancer Treated with Atezolizumab

Other: Sample collection

Interventions

Sample collection OTHER

1. .Analysis of immune marker using FACS before treatment and Cycle1, Cycle2, Cycle3 and the time of disease progression. 2. .Multiplexed biomarker analysis of tumor and immune cells in tumor microenvironment (TME) at pre-treatment and progression (Pre-treatment biopsy is mandatory but biopsy is optional for disease progression) 3\. microbiome Pretreatment stool sample will be collected. (Stool sample is optional) 4.Genetic analysis For RNAseq or exome seq, biopsied tissue at baseline or progression are optional. 4.Single cell RNA sequencing (scRNA-seq) scRNA-seq will be performed by collecting selectively tissues from pre-treatment tumor biopsies and at relapse/acquired resistance tumor biopsies. Screening and treatment biopsies are optional.

Non-Small Cell Lung Cancer Treated with Atezolizumab

Eligibility Criteria

• Age: 20 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Non-Small Cell Lung Cancer Treated with Atezolizumab

You may qualify if:

• Signed Written Informed Consent
• a) Subjects must have signed and dated an IRB/IEC-approved written informed consent form in accordance with regulatory and institutional guidelines.
• Target Population
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0-1
• Subjects with histologically- or cytologically-documented NSCLC who presented with Stage IIIB/Stage IV disease and who have relapsed after treatment for stage IIIB/stage IV disease following chemotherapy, radiation therapy, or surgical resection.
• Subjects must have disease progression or recurrence during or after at least 1 systemic therapy for advanced or metastatic disease.
• i) Each subsequent line of therapy must be preceded by disease progression. ii) Subjects who received platinum-containing adjuvant, neoadjuvant or definitive chemoradiation therapy given for locally advanced disease, and developed recurrent (local or metastatic) disease within 6 months of completing therapy are eligible.
• iii) Subjects with recurrent disease \> 6 months after completing a platinum-containing adjuvant, neoadjuvant or definitive chemoradiation therapy given for locally advanced disease, who also subsequently progressed during or after a systemic regimen given to treat the recurrence, are eligible.
• d) Prior chemotherapy or TKI therapy must have been completed at least 1 week before study drug administration. All AEs due to prior chemotherapy or immunotherapy have either returned to baseline or stabilized.
• e) Prior palliative radiotherapy must have been completed at least 7 days prior to study drug administration.
• f) Subjects are eligible if CNS metastases are treated or subjects have neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 14 days prior to enrollment. In addition, subjects must either be off corticosteroids or on a stable dose or decreasing dose of ≤ 10 mg daily prednisone (or equivalent) g) Screening laboratory values must meet the following criteria prior to commencement of treatment: i) WBCs ≥ 2000/µL ii) Neutrophils ≥1500/µL iii) Platelets ≥ 100 X10³/µL iv) Hemoglobin ≥ 9.0 g/dL v) Serum creatinine of ≤ 1.5 X ULN or creatinine clearance (CrCl) \> 40 mL/minute (using Cockcroft/Gault formula)
• (1). Female CrCl= \[(140- age in years) X weight in kg X 0.85) ÷ (72 X serum creatinine in mg/ dL)\] (2). Male CrCl= \[(140- age in years) X weight in kg X 1.00) ÷ (72 X serum creatinine in mg/ dL)\] vi) AST and ALT ≤ 3 X ULN (In the case of patients with liver metastasis, AST (GOT) and ALT (GPT) ≤ 5.0 times the upper limit of normal range) vii) Total bilirubin ≤ 1.5 X ULN (except subjects with Gilbert Syndrome, who must have total bilirubin \< 3.0 mg/dL) h) Subjects with Type I diabetes mellitus, residual hypothyroidism due to an autoimmune condition requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
• i) Subjects with available PD-L1 immunohistochemistry (IHC) result could be enrolled regardless of the results of PD-L1 IHC.
• j) Subject re-enrollment: This study permits the re-enrollment of a subject who has discontinued the study as a pre-treatment failure (ie, subject has not been treated). If re- enrolled, the subject must be re-consented.
• \. Age and Reproductive Status

You may not qualify if:

• a) Target Disease Exceptions i) Subjects with ECOG PS ≥ 2 ii) Subjects with untreated CNS metastases are excluded. Subjects are eligible if CNS metastases are treated or subjects have neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to enrollment. In addition, subjects must either be off corticosteroids or on a stable or decreasing dose of ≤ 10 mg daily prednisone (or equivalent).
• iii) Subjects with carcinomatous meningitis are excluded iv) Subjects with \< 6 weeks life expectancy b) Medical History and Concurrent Diseases i) Subjects with known active, known, or suspected autoimmune disease which the investigator considers significant ii) Subjects with a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of first dose of study drug administration. Inhaled or topical steroids and adrenal replacement steroid doses \> 10 mg daily prednisone equivalent are permitted in the absence of active autoimmune disease.
• iii) Subjects who received prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CT137 or anti-CTLA-4 antibody including ipilimumab or any other antibody or drug specifically targeting T cell costimulation or checkpoint pathways iv) Subjects with interstitial lung disease. v) Other active malignancy requiring concurrent intervention vi) Subjects with previous malignancies (except non-melanoma skin cancers and the following in situ cancers: bladder, gastric, colon, endometrial, cervical/dysplasia, melanoma, or breast) are excluded unless a complete remission was achieved at least 1 year prior to study entry AND no additional therapy is required during the study period vii) Any serious or uncontrolled medical disorder or active infection that, in the opinion of the investigator, may increase the risk associated with study participation, study drug administration, or would impair the ability of the subject to receive protocol therapy viii) All toxicities attributed to prior anti-cancer therapy other than alopecia and fatigue must have resolved to Grade 1 (NCI CTCAE version 5) or baseline before administration of study drug ix) Subjects must have recovered from the effects of major surgery or significant traumatic injury at least 14 days before the first dose of study treatment x) Known alcohol or drug abuse

Sponsors & Collaborators

• Yonsei University: lead

Study Sites (1)

Yonsei Severance Hospital

Seoul, South Korea

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Specimen Handling

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 28, 2020
• First Posted: March 18, 2020
• Study Start: April 8, 2020
• Primary Completion: January 26, 2025
• Study Completion: January 26, 2025
• Last Updated: February 6, 2026

Record last verified: 2025-02

Locations

KR (1)