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

• Sponsor: Chonnam National University Hospital (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT04059887
• Collaborator: Roche Pharma AG (Industry)
• Enrollment: 100
• Location: 1
• Arm: 1
• Anticipated Duration (Months): 30.4
• Patients Per Site Per Month: 3.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Lung Neoplasm Malignant	Drug: Atezolizumab Injection [Tecentriq]	Phase 4

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 100 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Evaluation of Blood Tumor Mutation Burden (TMB) for Improved Efficacy of Atezolizumab in 2nd Line Non-small Cell Lung Cancer (NSCLC) [BUDDY]
• Actual Study Start Date: Dec 18, 2019
• Anticipated Primary Completion Date: Dec 31, 2021
• Anticipated Study Completion Date: Jun 30, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Atezolizumab Atezolizumab 1200 mg will be administrated every 3 week cycle	Drug: Atezolizumab Injection [Tecentriq]; Blood sampling will be performed before and after 3rd cycle of atezolizumab for evaluation of tumor mutation burden; Other Names: Tecentriq

Outcome Measures

Primary Outcome Measures

1. 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

1. 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

2. Safety profile [Through study completion, an average of 1 year]

   Incidence of Treatment-related Adverse Events as assessed by CTCAE version 4

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

1. 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

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

3. Life expectancy ≥ 12 weeks

4. 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.

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

2. 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.

1. Uncontrolled idiopathic pulmonary fibrosis or drug-induced pneumonitis

2. 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.

1. Patient with a known hypersensitivity to atezolizumab or any of the excipients

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Chonnam National University Hwasun Hospital	Jeollanam-do	전라남도	Korea, Republic of	58128

Sponsors and Collaborators

• Chonnam National University Hospital
• Roche Pharma AG

Investigators

• Principal Investigator: In-Jae Oh, MD, PhD, Chonnam National Univeristy Hwasun Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: In-Jae, Oh, MD, Professor, Chonnam National University Hospital
• ClinicalTrials.gov Identifier: NCT04059887
• Other Study ID Numbers: H2019-0351
• First Posted: Aug 16, 2019
• Last Update Posted: Jan 27, 2021
• Last Verified: Jan 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by In-Jae, Oh, MD, Professor, Chonnam National University Hospital: Non-small cell lung cancer; Immune checkpoint inhibitor; Tumor mutation burden
• Additional relevant MeSH terms: Lung Neoplasms; Neoplasms; Atezolizumab

Study Results

No Results Posted as of Jan 27, 2021