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

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

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.

Study Overview

• Status: Completed
• Conditions: Lung Neoplasm Malignant
• Intervention / Treatment: Drug: Atezolizumab Injection [Tecentriq]

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 Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: In-Jae Oh, MD, PhD; Phone Number: +82 61 379 7617; Email: droij@chonnam.ac.kr

Study Locations

• Korea, Republic of
  • Jeollanam-do
    • Hwasun, Jeollanam-do, Korea, Republic of, 58128
      • Chonnam National University Hwasun Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Chonnam National University Hospital
• Collaborators: Roche Pharma AG

Publications and helpful links

General Publications

• Kim ST, Cristescu R, Bass AJ, Kim KM, Odegaard JI, Kim K, Liu XQ, Sher X, Jung H, Lee M, Lee S, Park SH, Park JO, Park YS, Lim HY, Lee H, Choi M, Talasaz A, Kang PS, Cheng J, Loboda A, Lee J, Kang WK. Comprehensive molecular characterization of clinical responses to PD-1 inhibition in metastatic gastric cancer. Nat Med. 2018 Sep;24(9):1449-1458. doi: 10.1038/s41591-018-0101-z. Epub 2018 Jul 16.
• Gandara DR, Paul SM, Kowanetz M, Schleifman E, Zou W, Li Y, Rittmeyer A, Fehrenbacher L, Otto G, Malboeuf C, Lieber DS, Lipson D, Silterra J, Amler L, Riehl T, Cummings CA, Hegde PS, Sandler A, Ballinger M, Fabrizio D, Mok T, Shames DS. Blood-based tumor mutational burden as a predictor of clinical benefit in non-small-cell lung cancer patients treated with atezolizumab. Nat Med. 2018 Sep;24(9):1441-1448. doi: 10.1038/s41591-018-0134-3. Epub 2018 Aug 6.

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 18, 2019
• Primary Completion (ACTUAL): December 31, 2021
• Study Completion (ACTUAL): June 30, 2022

Study Registration Dates

• First Submitted: August 9, 2019
• First Submitted That Met QC Criteria: August 15, 2019
• First Posted (ACTUAL): August 16, 2019

Study Record Updates

• Last Update Posted (ACTUAL): February 8, 2023
• Last Update Submitted That Met QC Criteria: February 6, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Non-small cell lung cancer; Immune checkpoint inhibitor; Tumor mutation burden
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms; Lung Neoplasms; Antineoplastic Agents; Atezolizumab
• Other Study ID Numbers: H2019-0351

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No