Atezolizumab and Cobimetinib in Treating Patients with Metastatic, Recurrent, or Refractory Non-small Cell Lung Cancer
18 Years and older, Male and Female
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.
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.
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.
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.
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.
- 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
Treatment Sites in Georgia
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