Clinical Trials /

Evaluation of Blood TMB for the Efficacy of Atezolizumab [BUDDY]

NCT04059887

Description:

This is single arm, prospective, multi-center, cohort study to evaluate blood TMB for improved efficacy of atezolizumab in locally advanced or metastatic NSCLC at the study enrollment who failed one or more prior lines of chemotherapy including at least 1 platinum-based.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 4

Trial Eligibility

Document

Title

  • Brief Title: Evaluation of Blood TMB for the Efficacy of Atezolizumab [BUDDY]
  • Official Title: Evaluation of Blood Tumor Mutation Burden (TMB) for Improved Efficacy of Atezolizumab in 2nd Line Non-small Cell Lung Cancer (NSCLC) [BUDDY]

Clinical Trial IDs

  • ORG STUDY ID: H2019-0351
  • NCT ID: NCT04059887

Conditions

  • Lung Neoplasm Malignant

Interventions

DrugSynonymsArms
Atezolizumab Injection [Tecentriq]TecentriqAtezolizumab

Purpose

This is single arm, prospective, multi-center, cohort study to evaluate blood TMB for improved efficacy of atezolizumab in locally advanced or metastatic NSCLC at the study enrollment who failed one or more prior lines of chemotherapy including at least 1 platinum-based.

Detailed Description

      Atezolizumab is approved as the treatment of patients with locally advanced or metastatic
      NSCLC who have disease progression during or following platinum-containing chemotherapy by
      the Ministry of Food and Drug Safety (MFDS) and the treatment is available on the National
      Health Insurance Service in South Korea. Patients will be treated with atezolizumab until
      loss of clinical benefit or unmanageable toxicity as routine practice.

      In this study, the investigators will register patients who have a plan to be treated with
      atezolizumab as MFDS approval condition and meet study inclusion and exclusion criteria. The
      investigators will collect study related information during routine practice and collect
      blood and/or tissue(optional) samples to conduct the study.

      Tumor assessment will be performed by investigator on the base of RECIST (version 1.1) and
      related information will be collected until disease progression for patients who have
      discontinued treatment. However, it will be collected until treatment discontinuation for
      patients who continue to receive atezolizumab following initial disease progression.
    

Trial Arms

NameTypeDescriptionInterventions
AtezolizumabExperimentalAtezolizumab 1200 mg will be administrated every 3 week cycle
  • Atezolizumab Injection [Tecentriq]

Eligibility Criteria

        Inclusion Criteria:

          1. Signed Informed Consent Form

          2. Ability to comply with protocol

          3. Aged ≥ 18 years

          4. Histologically or cytologically confirmed NSCLC that is locally advanced or metastatic
             (i.e., Stage IIIB not eligible for definitive chemoradiotherapy, Stage IV, or
             recurrent) NSCLC at the study enrollment

          5. Disease progression during or following treatment with a prior platinum-containing
             regimen for NSCLC

               -  Patients may have received one or more additional cytotoxic chemotherapy regimen.

               -  Patients with epidermal growth factor receptor (EGFR) or anaplastic lymphoma
                  kinase (ALK) genomic tumor aberrations should have disease progression on
                  approved therapy for these aberrations prior to receiving atezolizumab.

          6. Measurable disease, as defined by RECIST v1.1 Measurable disease is defined by the
             presence of at least one measurable lesion by RECIST v1.1

          7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 2

          8. Life expectancy ≥ 12 weeks

          9. Adequate hematologic and end organ function:

               -  Absolute neutrophil count (ANC) ≥ 1.0 x 109/L

               -  White blood cell (WBC) counts > 2.5 x 109/L

               -  Hemoglobin ≥ 8.0 g/dL

               -  Total bilirubin ≤ 2.5 X upper limit of normal (ULN) Patients with known Gilbert's
                  disease who have serum bilirubin level ≤ 3 x ULN may be enrolled.

               -  Aspartate aminotransferase (AST), alanine transaminase (ALT), and alkaline
                  phosphatase ≤ 2.5 × ULN, with the following exceptions:

        Patients with documented liver metastases: AST and ALT ≤ 5 × ULN Patients with documented
        liver or bone metastases: alkaline phosphatase ≤ 5 × ULN

        Exclusion Criteria:

          1. Active or untreated central nervous system (CNS) metastases Patients with a history of
             treated CNS metastases that are asymptomatic are eligible

          2. Malignancies other than NSCLC within 5 years prior to study enrollment, with the
             exception of those with a negligible risk of metastasis or death and treated with
             expected curative outcome (such as adequately treated carcinoma in situ of the cervix,
             basal or squamous cell skin cancer, localized prostate cancer treated with curative
             intent, or ductal carcinoma in situ treated surgically with curative intent)

          3. Pregnant and lactating women

             • Women of childbearing potential should use effective contraception during treatment
             with atezolizumab and for at least 5 months following the last dose.

          4. Significant cardiovascular disease, such as New York Heart Association cardiac disease
             (Class II or greater), myocardial infarction within 3 months prior to study enrollment

          5. Patients with autoimmune disorder or a history of chronic or recurrent autoimmune
             disorder

               -  Patients with a history of autoimmune-mediated hypothyroidism on a stable dose of
                  thyroid replacement hormone may be eligible for this study.

               -  Patients with controlled Type 1 diabetes mellitus on a stable insulin regimen may
                  be eligible for this study.

          6. Uncontrolled idiopathic pulmonary fibrosis or drug-induced pneumonitis

          7. Treatment with systemic corticosteroids or other systemic immunosuppressive
             medications (including prednisone, dexamethasone, cyclophosphamide, azathioprine,
             methotrexate, thalidomide, and anti-tumor necrosis factor agents) within 2 weeks prior
             to study enrollment

             • Treatment with inhaled corticosteroid or megesterol acetate is permitted.

          8. Patient with a known hypersensitivity to atezolizumab or any of the excipients
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective response rate (ORR)
Time Frame:At the end of cycle 3 (each cycle is 21 days)
Safety Issue:
Description:ORR between blood TMB-High vs. Low group

Secondary Outcome Measures

Measure:Progression-free survival (PFS)
Time Frame:At the end of cycle 3 (each cycle is 21 days)
Safety Issue:
Description:PFS in Intention-to-treat (ITT) population and subgroups according to blood TMB and programmed cell death-1 (PDL1) status
Measure:Safety profile
Time Frame:Through study completion, an average of 1 year
Safety Issue:
Description:Incidence of Treatment-related Adverse Events as assessed by CTCAE version 4

Details

Phase:Phase 4
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Chonnam National University Hospital

Trial Keywords

  • Non-small cell lung cancer
  • Immune checkpoint inhibitor
  • Tumor mutation burden

Last Updated

January 12, 2020