Atezolizumab and Cobimetinib in Treating Patients With Metastatic, Recurrent, or Refractory Non-small Cell Lung Cancer
A Phase 2 Study of Atezolizumab and Cobimetinib in PD-1/PD-L1 Inhibitor Resistant or Refractory Non-Small Cell Lung Cancer
3 other identifiers
interventional
51
1 country
18
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Nov 2018
Longer than P75 for phase_2
18 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 25, 2018
CompletedFirst Posted
Study publicly available on registry
July 26, 2018
CompletedStudy Start
First participant enrolled
November 29, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 14, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
October 3, 2026
ExpectedOctober 7, 2025
October 1, 2025
6.6 years
July 25, 2018
October 4, 2025
Conditions
Outcome Measures
Primary Outcomes (1)
Durable response rate to therapy
Will be presented with descriptive statistics. A durable response is defined as a response meeting Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria in a patient whose response duration was of at least 6 months.
Up to 90 days
Secondary Outcomes (6)
Overall response rate
Up to 90 days
Duration of response
Up to 90 days
Progression free survival (PFS)
Time from start of treatment to time of progression or death, whichever occurs first, assessed up to 90 days
Overall survival (OS)
From start of study treatment to time of death, assessed up to 90 days
Grade 3 and 4 toxicities
Up to 90 days
- +1 more secondary outcomes
Study Arms (1)
Treatment (atezolizumab, cobimetinib)
EXPERIMENTALPatients receive atezolizumab IV over 30-60 minutes on days 1, and cobimetinib PO QD on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unaccepted toxicity. Patients also undergo a CT scan, MRI, biopsy, and collection of blood throughout the trial.
Interventions
Given IV
Undergo biopsy
Undergo collection of blood
Given PO
Undergo CT scan
Undergo MRI
Eligibility Criteria
You may qualify if:
- Patients must have histologically or cytologically confirmed metastatic or recurrent non-small cell lung cancer (any histology is permitted)
- Presence of a mutation in KRAS as detected by a Clinical Laboratory Improvement Act (CLIA)-approved assay is required for patients enrolled in cohort 1; central validation is not required for enrollment
- Absence of a mutation in KRAS (KRAS wild type) is required for patients enrolled in cohort 2; central validation is not required for enrollment but KRAS mutation status must be known, regardless of histology
- Patients must have primary resistance to anti-PD-1 or anti-PD-L1 therapy, given as monotherapy or in combination with other agents; patients must have experienced progressive disease within 6 months (180 days) of initiating treatment with a PD-1/PD-L1 inhibitor
- Anti-PD-1 or anti-PD-L1 therapy does not need to be the most recent therapy prior to study enrollment
- Patients with a sensitizing alteration in EGFR, ALK or ROS1 are eligible provided they have experienced disease progression or intolerance to treatment with an approved EGFR, ALK or ROS1 inhibitor, respectively; patients who have received investigational inhibitors may be eligible following discussion with the study principal investigator (PI)
- Patients must have disease amenable to core biopsy and be willing to undergo the required research biopsies
- Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \>= 20 mm (\>= 2 cm) by chest x-ray or as \>= 10 mm (\>= 1 cm) with CT scan, MRI, or calipers by clinical exam
- Age \>= 18 years
- Because no dosing or adverse event data are currently available on the use of atezolizumab in combination with cobimetinib in patients \< 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials
- Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
- Leukocytes \>= 2,500/mcL
- Absolute neutrophil count \>= 1,000/mcL
- Platelets \>= 100,000/mcL
- Hemoglobin \>= 8 g/dL
- +8 more criteria
You may not qualify if:
- Patients who have not recovered from clinically significant adverse events (other than alopecia) due to prior anti-cancer therapy
- Treatment with any investigational agent within 4 weeks prior to cycle 1, day 1
- Treatment with systemic immunosuppressive medications (including, but not limited to, prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor \[anti-TNF\] agents) within 2 weeks prior to cycle 1, day 1
- Patients who have received acute, low dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled
- The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed
- Patients with symptomatic central nervous system (CNS) metastases are excluded
- Patients with asymptomatic untreated CNS disease may be enrolled, provided all of the following criteria are met:
- Evaluable or measurable disease outside the CNS
- No metastases to brain stem, midbrain, pons, medulla, cerebellum, or within 10 mm of the optic apparatus (optic nerves and chiasm)
- No history of intracranial hemorrhage or spinal cord hemorrhage
- No ongoing requirement for dexamethasone for CNS disease; patients on a stable dose of anticonvulsants are permitted
- No neurosurgical resection or brain biopsy within 28 days prior to cycle 1, day 1
- Patients with asymptomatic treated CNS metastases may be enrolled, provided all the criteria listed above are met as well as the following:
- Radiographic demonstration of improvement upon the completion of CNS-directed therapy and no evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study
- No stereotactic radiation or whole-brain radiation within 28 days prior to cycle 1, day 1
- +31 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (18)
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, 35233, United States
UC San Diego Moores Cancer Center
La Jolla, California, 92093, United States
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, 20007, United States
Moffitt Cancer Center
Tampa, Florida, 33612, United States
Emory University Hospital Midtown
Atlanta, Georgia, 30308, United States
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322, United States
Emory Saint Joseph's Hospital
Atlanta, Georgia, 30342, United States
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, 48201, United States
Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center
Lebanon, New Hampshire, 03756, United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903, United States
NYP/Weill Cornell Medical Center
New York, New York, 10065, United States
Wake Forest University at Clemmons
Clemmons, North Carolina, 27012, United States
Hayworth Cancer Center
High Point, North Carolina, 27262, United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232, United States
University of Virginia Cancer Center
Charlottesville, Virginia, 22908, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Stephen V Liu
JHU Sidney Kimmel Comprehensive Cancer Center LAO
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 25, 2018
First Posted
July 26, 2018
Study Start
November 29, 2018
Primary Completion
July 14, 2025
Study Completion (Estimated)
October 3, 2026
Last Updated
October 7, 2025
Record last verified: 2025-10