This phase II trial studies how well atezolizumab and cobimetinib work in treating patients with non-small cell lung cancer that has spread from where it first started (primary site) to other places in the body (metastatic), has come back (recurrent), or does not respond to treatment (refractory). Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cobimetinib is used in patients whose cancer has a mutated (changed) form of a gene called BRAF. It is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply. This helps slow or stop the spread of cancer cells. Giving atezolizumab and cobimetinib may work better in treating patients with non-small cell lung cancer.
PRIMARY OBJECTIVE: I. To evaluate durable overall response rate with atezolizumab plus cobimetinib in patients with metastatic non-small cell lung cancer (NSCLC) resistant or refractory to prior PD-1 or PD-L1 therapy. SECONDARY OBJECTIVES: I. To evaluate the overall response rate of atezolizumab plus cobimetinib in patients with metastatic NSCLC resistant or refractory to prior PD-1 or PD-L1 therapy. II. To evaluate the progression-free survival (PFS) of atezolizumab plus cobimetinib in patients with metastatic NSCLC resistant or refractory to prior PD-1 or PD-L1 therapy. III. To evaluate the overall survival (OS) of atezolizumab plus cobimetinib in patients with metastatic NSCLC resistant or refractory to prior PD-1 or PD-L1 therapy. IV. To evaluate the duration of response (DOR) of atezolizumab plus cobimetinib in patients with metastatic NSCLC resistant or refractory to prior PD-1 or PD-L1 therapy. V. To evaluate the grade 3 and 4 toxicity rate in patients with metastatic NSCLC resistant or refractory to prior PD-1 or PD-L1 therapy when treated with atezolizumab plus cobimetinib. EXPLORATORY OBJECTIVES: I. To evaluate the consequences of treatment with atezolizumab plus cobimetinib on the tumor microenvironment in patients with metastatic NSCLC resistant or refractory to prior PD-1 or PD-L1 therapy. II. To correlate genomic characteristics including tumor mutation burden to response to therapy with atezolizumab plus cobimetinib in patients with metastatic NSCLC resistant or refractory to prior PD-1 or PD-L1 therapy. OUTLINE: Patients receive atezolizumab intravenously (IV) over 30-60 minutes on day 1 and cobimetinib orally (PO) once daily (QD) on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unaccepted toxicity. Patients also undergo a computed tomography (CT) scan, magnetic resonance imaging (MRI), biopsy, and collection of blood throughout the trial. After completion of study treatment, patients are followed up for 90 days.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
53
Given IV
Undergo biopsy
Undergo collection of blood
Given PO
Undergo CT scan
Undergo MRI
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, United States
UC San Diego Moores Cancer Center
La Jolla, California, United States
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, United States
Moffitt Cancer Center
Tampa, Florida, United States
Emory University Hospital Midtown
Atlanta, Georgia, United States
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, United States
Emory Saint Joseph's Hospital
Atlanta, Georgia, United States
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, United States
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
Lebanon, New Hampshire, United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, United States
...and 8 more locations
Number of Participants With a Durable Response
Response is defined as having a complete response (CR) (disappearance of all lesions) or partial response (PR) (\>= 30% decrease in the sum of target lesions) as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria. A durable response is defined as having a CR or PR response which lasts for at least 6 months.
Time frame: Up to 4.6 years
Number of Participants Experiencing a Disease Outcome
Disease outcomes are assessed by RECIST version 1.1 criteria and defined as complete response (CR) (disappearance of all lesions), partial response (PR) (\>= 30% decrease in the sum of target lesions), progressive disease (PD) (\>= 20% increase in the sum of target lesions, measurable increase in a non-target lesion, or appearance of a new lesion), or stable disease (SD) (between 20% increase and 30% decrease in the sum of lesions).
Time frame: Up to 4.6 years
Duration of Response
Response is complete response (disappearance of all lesions) or partial response (\>= 30% decrease in the sum of target lesions) as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Duration is how long that response lasted.
Time frame: Up to 4.6 years (1688 days)
Duration of Progression Free Survival (PFS)
Progression free survival is from the date of enrollment to the date of the first documented progressive disease (PD) (\>= 20% increase in the sum of target lesions, measurable increase in a non-target lesion, or appearance of a new lesion) as defined by RECIST v1.1 or death due to any cause, whichever occurs first. The date off study was used for participants who did not experience PD or death.
Time frame: Up to 4.6 years (1688 days)
Overall Survival (OS)
Overall survival is from the date enrolled on the study to the date the participant died. The date the participant completed study participant was used for participants who did not die.
Time frame: Up to 4.6 years (1688 days)
Number of Participants Experiencing Grade 3 and 4 Adverse Events
Adverse events will be assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 5.
Time frame: Up to 4.6 years
Biomarker Analysis
The analysis of biomarkers will also be descriptive given the limited sample sizes. Categorical data analysis methods such as Chi-square will be used to evaluate the correlation of baseline tumor mutation burden to response to therapy. Regression and correlation will be used for assessing the association between continuous variables such as tumor burden and other markers and patient characteristics such as age.
Time frame: Up to 90 days
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