AzTrials
AzTrials

Metastatic Lung Non-Small Cell CarcinomaPhase 2NCT03600701

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

A Phase 2 study testing Atezolizumab, Biopsy Procedure and Biospecimen Collection in people with Metastatic Lung Non-Small Cell Carcinoma and Recurrent Lung Non-Small Cell Carcinoma, run by National Cancer Institute (NCI) at 18 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Atezolizumab, Biopsy Procedure and Biospecimen Collection
Could I receive a placebo?
No, everyone receives an active treatment
How many people
53 participants
Where
18 sitesUnited States
Study dates
29 Nov 2018to 3 Oct 2027
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
Show all 23Show fewer
  • 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

Who cannot join

  • 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
Show all 46Show fewer
  • 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
  • Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease
  • Patients with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen [HBsAg] test and a positive anti-HBc [antibody to hepatitis B core antigen] antibody test) are eligible
  • Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA)
  • History or risk of autoimmune disease, including, but not limited to, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, autoimmune hemolytic anemia, Wegener's granulomatosis, Sjogren's syndrome, Bell's palsy, Guillain-Barre syndrome, multiple sclerosis, vasculitis, or glomerulonephritis
  • Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone may be eligible
  • Patients with controlled type 1 diabetes mellitus on a stable insulin regimen may be eligible
  • Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions:
  • Patients with psoriasis must have a baseline ophthalmologic exam to rule out ocular manifestations
  • Rash must cover less than 10% of body surface area (BSA)
  • Disease is well controlled at baseline and only requiring low potency topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, flucinolone 0.01%, desonide 0.05%, aclometasone dipropionate 0.05%)
  • No acute exacerbations of underlying condition within the last 12 months (not requiring psoralen plus ultraviolet A radiation [PUVA], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors; high potency or oral steroids)
  • History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest computed tomography (CT) scan; history of radiation pneumonitis in the radiation field (fibrosis) is permitted
  • Any significant active infection requiring treatment within 14 days prior to cycle 1, day 1
  • Major surgical procedure within 28 days prior to cycle 1, day 1 or anticipation of need for a major surgical procedure during the course of the study
  • Administration of a live, attenuated vaccine within 4 weeks before cycle 1, day 1 or anticipation that such a live, attenuated vaccine will be required during the study and up to 5 months after the last dose of atezolizumab
  • Influenza vaccination should be given during influenza season only (approximately October to March); patients must not receive live, attenuated influenza vaccine within 4 weeks prior to cycle 1, day 1 or at any time during the study
  • Uncontrolled pleural or pericardial effusion or ascites requiring recurrent drainage procedures
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, active tuberculosis (TB), symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study because both atezolizumab and cobimetinib are expected to cause fetal harm if used during pregnancy; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with cobimetinib or atezolizumab, breastfeeding should be discontinued if the mother is treated with either therapy; these potential risks may also apply to other agents used in this study
  • Inability or unwillingness to swallow pills
  • History of malabsorption syndrome or other condition that would interfere with enteral absorption

Trial locations and contacts

18 sites in 1 country.

18 sites in 1 country

United States18 sites

  • Emory University Hospital Midtown

    Atlanta, Georgia, 30308

  • Emory University Hospital/Winship Cancer Institute

    Atlanta, Georgia, 30322

  • Emory Saint Joseph's Hospital

    Atlanta, Georgia, 30342

  • University of Alabama at Birmingham Cancer Center

    Birmingham, Alabama, 35233

  • University of Virginia Cancer Center

    Charlottesville, Virginia, 22908

  • Wake Forest University at Clemmons

    Clemmons, North Carolina, 27012

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • Wayne State University/Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • Hayworth Cancer Center

    High Point, North Carolina, 27262

  • UC San Diego Moores Cancer Center

    La Jolla, California, 92093

  • Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center

    Lebanon, New Hampshire, 03756

  • Rutgers Cancer Institute of New Jersey

    New Brunswick, New Jersey, 08903

  • NYP/Weill Cornell Medical Center

    New York, New York, 10065

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • UPMC Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232

  • Moffitt Cancer Center

    Tampa, Florida, 33612

  • MedStar Georgetown University Hospital

    Washington D.C., District of Columbia, 20007

  • Wake Forest University Health Sciences

    Winston-Salem, North Carolina, 27157

Other trials in United States

About this study

Official title: A Phase 2 Study of Atezolizumab and Cobimetinib in PD-1/PD-L1 Inhibitor Resistant or Refractory Non-Small Cell Lung Cancer

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. 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:

  1. 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.

  1. 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:

  1. 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.

Being tested
Atezolizumab, Biopsy Procedure, Biospecimen Collection, Cobimetinib, Computed Tomography
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Lung Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AtezolizumabDrug

    Also called MPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A

    Given IV

  • Biopsy ProcedureProcedure or surgery

    Also called Biopsy, BIOPSY_TYPE, Bx

    Undergo biopsy

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

    Undergo collection of blood

  • CobimetinibDrug

    Also called Cotellic, GDC 0973, GDC-0973, GDC0973

    Given PO

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT scan

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan

    Undergo MRI

Study groups in NCT03600701
Study groupRoleWhat they receive
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.
Receives: Drug: Atezolizumab; Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Drug: Cobimetinib; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to 4.6 years

Secondary outcomes (6)

  1. 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).

    Measured: Up to 4.6 years

  2. 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.

    Measured: Up to 4.6 years (1688 days)

  3. 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.

    Measured: Up to 4.6 years (1688 days)

  4. 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.

    Measured: Up to 4.6 years (1688 days)

  5. 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.

    Measured: Up to 4.6 years

  6. 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.

    Measured: Up to 90 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Jul 2018
  2. Study start29 Nov 2018
  3. Primary completion14 Jul 2025
  4. Study completion3 Oct 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
53 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03600701
Sponsor's protocol ID
NCI-2017-01812
Other IDs
NCI-2017-01812, 10166, 10166, UM1CA186691
Status last verified
Oct 2026
First submitted
25 Jul 2018
Last updated
27 Oct 2026
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Atezolizumab, Biopsy Procedure and Biospecimen Collection in people with Metastatic Lung Non-Small Cell Carcinoma and Recurrent Lung Non-Small Cell Carcinoma, run by National Cancer Institute (NCI) at 18 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 46 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 27 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 18 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Aug 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With a Durable Response (time frame: Up to 4.6 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03600701.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Oct 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in