Clinical trial NCT02848651: A Study of Atezolizumab as First-line Monotherapy for Advanced or Metastatic Non-Small Cell Lung Cancer
Official title: A Phase II Single-Arm Study of Atezolizumab Monotherapy in Locally Advanced or Metastatic Non-Small Cell Lung Cancer: Clinical Evaluation of Novel Blood-Based Diagnostics
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non-Small Cell Lung Cancer
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2016-07-28
Enrollment: 153
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This was a Phase II, open-label, prospective, multicenter study designed to evaluate the efficacy and safety of single-agent atezolizumab as a first-line therapy in participants with locally advanced or metastatic non-small cell lung cancer (NSCLC). In addition, the primary biomarker objective was to measure blood tumor mutational burden (bTMB) and evaluate whether it can predict for improved clinical outcome with atezolizumab.


Eligibility criteria: Inclusion Criteria:

* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Histologically or cytologically confirmed Stage IIIB-IVB NSCLC
* For participants who have received prior neo-adjuvant/adjuvant chemotherapy or chemoradiotherapy with curative intent for non-metastatic disease: a treatment-free interval of at least 6 months prior to enrollment
* Participants with any programmed death-ligand 1 (PD-L1) test result by immunohistochemistry (IHC) are eligible for the study
* Participants without a PD-L1 test result are eligible for the study
* Measurable disease per RECIST v1.1
* Adequate hematologic and end-organ function
* Agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods among women of childbearing potential

Exclusion Criteria:

* Prior treatment with immunotherapy for any stage NSCLC, including early-stage (neoadjuvant or adjuvant) disease
* Participants with epidermal growth factor receptor (EGFR) sensitizing mutations and anaplastic lymphoma kinase (ALK) rearrangements
* Active central nervous system (CNS) metastases requiring treatment
* Spinal cord compression not definitively treated or not clinically stable
* Leptomeningeal disease
* Uncontrolled tumor-related pain
* Uncontrolled pleural, pericardial effusions, or ascites requiring recurrent drainage procedures
* Uncontrolled or symptomatic hypercalcemia
* Malignancies other than NSCLC within 5 years prior to enrollment, except for those curatively treated with negligible risk of metastasis or death
* Pregnant or lactating women
* History of autoimmune disease, significant pulmonary disease, or significant cardiovascular disease
* Positive human immunodeficiency virus (HIV) or hepatitis B or C
* Active tuberculosis
* Severe infection or major surgery within 4 weeks, or oral or IV antibiotics treatment within 2 weeks prior to enrollment
* Prior treatment with or hypersensitivity to study drug or related compounds
* Prior allogeneic bone marrow or solid organ transplant
* Administration of a live, attenuated vaccine within 4 weeks prior to enrollment
* Treatment with systemic immunostimulatory agents within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to enrollment
* Treatment with systemic corticosteroids or other systemic immunosuppressive medications within 2 weeks prior to enrollment

Primary outcomes:
measure: Percentage of Participants With Objective Response Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Determined by Investigator
timeFrame: Baseline up to 32 months
measure: Progression-Free Survival (PFS) Per RECIST v1.1 as Determined by Investigator, by Positive Versus Negative bTMB Groups
timeFrame: Baseline up to 32 months
Secondary outcomes:
measure: Progression-Free Survival (PFS) Per RECIST v1.1 as Determined by Investigator
timeFrame: Baseline up to 32 months
measure: Duration of Response (DOR) Per RECIST v1.1 as Determined by Investigator
timeFrame: Baseline up to 32 months
measure: Disease Control Rate (DCR) Per RECIST v1.1 as Determined by Investigator
timeFrame: Baseline up to 32 months
measure: Overall Survival (OS)
timeFrame: From baseline until death (up to 32 months)
measure: Percentage of Participants With Adverse Events
timeFrame: Baseline up to 32 months
measure: Percentage of Participants Who Are Alive and Progression-Free (Per RECIST v1.1) at 6, 9, 12, and 18 Months by Various bTMB Quantiles
timeFrame: Months 6, 9, 12, and 18
measure: OS by Various bTMB Cutoff Points 16 and 20
timeFrame: From baseline until death (up to 32 months)
measure: Percentage of Participants With Objective Response (Per RECIST v1.1) by Various bTMB Quantiles
timeFrame: Baseline up to 32 months
Other outcomes:
Locations:
city: Fresno
country: United States
facility: Veterans Affairs Central California Health Care System
state: California
city: Hollywood
country: United States
facility: Memorial Regional Hospital
state: Florida
city: Orlando
country: United States
facility: Florida Hospital
state: Florida
city: Hoffman Estates
country: United States
facility: St. Alexius Medical Center
state: Illinois
city: Quincy
country: United States
facility: Quincy Medical Group; Canc Ctr at Blessing Hosp
state: Illinois
city: Indianapolis
country: United States
facility: Franciscan St. Francis Health; Research Services
state: Indiana
city: Wichita
country: United States
facility: Cancer Center of Kansas
state: Kansas
city: Ypsilanti
country: United States
facility: Michigan Cancer Rsch Cons
state: Michigan
city: Minneapolis
country: United States
facility: Virginia Piper Cancer Inst
state: Minnesota
city: Farmington
country: United States
facility: San Juan Oncology Associates
state: New Mexico
city: Bronx
country: United States
facility: Eastchester Center for Cancer Care
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Medical Center
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Institute-Carolinas Medical Center; Levine Cancer Institute-Carolinas Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
city: Philadelphia
country: United States
facility: Cancer Treatment Centers of America - Eastern Regional Medical Center
state: Pennsylvania
city: Sioux Falls
country: United States
facility: Avera Research Institute
state: South Dakota
city: Dallas
country: United States
facility: Univ of Texas SW Medical Ctr
state: Texas
city: Falls Church
country: United States
facility: Inova Health Care Services
state: Virginia
city: Lacey
country: United States
facility: Western WA Oncology Inc PS
state: Washington
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Kim ES, Velcheti V, Mekhail T, Yun C, Shagan SM, Hu S, Chae YK, Leal TA, Dowell JE, Tsai ML, Dakhil CSR, Stella P, Jin Y, Shames DS, Schleifman E, Fabrizio DA, Phan S, Socinski MA. Blood-based tumor mutational burden as a biomarker for atezolizumab in non-small cell lung cancer: the phase 2 B-F1RST trial. Nat Med. 2022 May;28(5):939-945. doi: 10.1038/s41591-022-01754-x. Epub 2022 Apr 14.