Atezolizumab and Cobimetinib in Treating Patients With Metastatic, Recurrent, or Refractory Non-small Cell Lung Cancer

Running, not enrolling · Phase 2

Conditions studied: Metastatic Lung Non-Small Cell Carcinoma, Recurrent Lung Non-Small Cell Carcinoma, Refractory Lung Non-Small Cell Carcinoma, Stage IV Lung Cancer AJCC v8

In brief

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.

Key facts

Study ID

NCT03600701

Run by

National Cancer Institute (NCI)

People needed

51

Starts

2018-11-29

Expected to finish

2026-10-03

Last updated by the study team

2025-10-07

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

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
• Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (however, patients with known Gilbert disease who have serum bilirubin level =< 3 x upper limit of normal [ULN] may be enrolled)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x ULN (AST and/or ALT =< 5 x ULN for patients with liver involvement)
• Alkaline phosphatase =< 2.5 x ULN (=< 5 x ULN for patients with documented liver involvement or bone metastases)
• Creatinine clearance >= 30 mL/min/1.73 m\^2 by Cockcroft-Gault
• Institutional normalized ratio (INR) and partial thromboplastin time (aPTT) =< 1.5 x ULN; (this applies only to patients who do not receive therapeutic anticoagulation; patients receiving therapeutic anticoagulation, such as low-molecular-weight heparin or warfarin, should be on a stable dose)
• Administration of atezolizumab or cobimetinib may have an adverse effect on pregnancy and poses a risk to the human fetus, including embryo-lethality; women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 5 months (150 days) after the last dose of study agent; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
• Ability to understand and the willingness to sign a written informed consent document
• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial

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
• Screening CNS radiographic study >= 4 weeks from completion of radiotherapy and >= 2 weeks from discontinuation of corticosteroids
• Has a known concurrent malignancy that is expected to require active treatment within two years, or may interfere with the interpretation of the efficacy and safety outcomes of this study in the opinion of the treating investigator; superficial bladder cancer, non-melanoma skin cancers, or low grade prostate cancer not requiring therapy should not exclude participation in this trial
• Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to atezolizumab or cobimetinib
• History of congenital long QT syndrome or corrected QT interval (QTc) by Fridericia Formula > 450 msec within 28 days of cycle 1, day 1
• Cardiac ejection fraction below institutional lower limit of normal (LLN) or below 50%, whichever is lower, as determined by echocardiogram or multigated acquisition (MUGA) scan within 4 weeks of cycle 1, day 1
• History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment, central serous chorioretinopathy, retinal vein occlusion (RVO), or neovascular macular degeneration
• Any grade 3 or above hemorrhage or bleeding event within 4 weeks prior to initiation of study treatment
• History of stroke, reversible ischemic neurological defect, or transient ischemic attack within 6 months prior to initiation of study treatment
• Patients receiving any medications or substances that are strong or moderate inhibitors or inducers of CYP3A4 enzymes are ineligible; these include St. John's wort or hyperforin (potent CYP3A4 enzyme inducer) and grapefruit juice (potent cytochrome P450 CYP3A4 enzyme inhibitor); because the lists of these agents are constantly changing, it is important to regularly consult medical reference texts such as the Physicians' Desk Reference may also provide this information; as part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product

Where it is running

• 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
• NYP/Weill Cornell Medical Center — New York, New York, United States
• Wake Forest University at Clemmons — Clemmons, North Carolina, United States
• Hayworth Cancer Center — High Point, North Carolina, United States
• Wake Forest University Health Sciences — Winston-Salem, North Carolina, United States
• Ohio State University Comprehensive Cancer Center — Columbus, Ohio, United States
• University of Oklahoma Health Sciences Center — Oklahoma City, Oklahoma, United States
• University of Pittsburgh Cancer Institute (UPCI) — Pittsburgh, Pennsylvania, United States
• University of Virginia Cancer Center — Charlottesville, Virginia, United States

Full record on ClinicalTrials.gov

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