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

Phase 4

Completed

• Conditions: Lung Neoplasm Malignant
• Interventions: Drug: Atezolizumab Injection [Tecentriq]

• Registration Number: NCT04059887
• Lead Sponsor: Chonnam National University Hospital

Brief Summary

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.

Study Timeline

• Study First Submitted: 2019-08-09
• Study First Submitted QC: 2019-08-15
• Study First Posted: 2019-08-16
• Study Start: 2019-12-18
• Primary Completion: 2021-12-31
• Study Completion: 2022-06-30
• Status Verified: 2023-02
• Last Update Submitted: 2023-02-06
• Last Update Posted: 2023-02-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 100

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Atezolizumab	Atezolizumab Injection [Tecentriq]	Atezolizumab 1200 mg will be administrated every 3 week cycle

Primary Outcome Measures

Name	Time	Method
Objective response rate (ORR)	At the end of cycle 3 (each cycle is 21 days)	ORR between blood TMB-High vs. Low group

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Chonnam National University Hwasun Hospital; 🇰🇷 Hwasun, Jeollanam-do, Korea, Republic of