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

NCT03600701 | Active Not Recruiting Phase 2 Results FDA Drug

• 3 other identifiers: NCI-2017-0181210166UM1CA186691
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 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.

Conditions

Metastatic Lung Non-Small Cell Carcinoma; Recurrent Lung Non-Small Cell Carcinoma; Refractory Lung Non-Small Cell Carcinoma; Stage IV Lung Cancer AJCC v8

Outcome Measures

Primary Outcomes (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.

  Up to 4.6 years

Secondary Outcomes (6)

• Number of Participants Experiencing a Disease Outcome

  Up to 4.6 years

• Duration of Response

  Up to 4.6 years (1688 days)

• Duration of Progression Free Survival (PFS)

  Up to 4.6 years (1688 days)

• Overall Survival (OS)

  Up to 4.6 years (1688 days)

• Number of Participants Experiencing Grade 3 and 4 Adverse Events

  Up to 4.6 years

Study Arms (1)

Treatment (atezolizumab, cobimetinib)

EXPERIMENTAL

Patients 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.

Drug: Atezolizumab; Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Drug: Cobimetinib; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging

Interventions

Atezolizumab DRUG

Given IV

Also known as: MPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A, MPDL328OA, RG 7446, RG-7446, RG7446, RO 5541267, RO-5541267, RO5541267, Tecentriq

Treatment (atezolizumab, cobimetinib)

Biopsy Procedure PROCEDURE

Undergo biopsy

Also known as: Biopsy, BIOPSY_TYPE, Bx

Treatment (atezolizumab, cobimetinib)

Cobimetinib DRUG

Given PO

Also known as: Cotellic, GDC 0973, GDC-0973, GDC0973, MEK Inhibitor GDC-0973, XL 518, XL-518, XL518

Treatment (atezolizumab, cobimetinib)

Biospecimen Collection PROCEDURE

Undergo collection of blood

Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

Treatment (atezolizumab, cobimetinib)

Computed Tomography PROCEDURE

Undergo CT scan

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Treatment (atezolizumab, cobimetinib)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Treatment (atezolizumab, cobimetinib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (18)

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, 35233, United States

Location

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Emory University Hospital Midtown

Atlanta, Georgia, 30308, United States

Location

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Emory Saint Joseph's Hospital

Atlanta, Georgia, 30342, United States

Location

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center

Lebanon, New Hampshire, 03756, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

NYP/Weill Cornell Medical Center

New York, New York, 10065, United States

Location

Wake Forest University at Clemmons

Clemmons, North Carolina, 27012, United States

Location

Hayworth Cancer Center

High Point, North Carolina, 27262, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

University of Virginia Cancer Center

Charlottesville, Virginia, 22908, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

atezolizumab; Biopsy; Specimen Handling; cobimetinib; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical

Results Point of Contact

• Title: Grants Administrator
• Organization: Johns Hopkins University/SKCCC

jmurra33@jhmi.edu

4439273568

Study Officials

• Stephen V Liu

  JHU Sidney Kimmel Comprehensive Cancer Center LAO

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

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: October 3, 2026
• Last Updated: September 1, 2026
• Results First Posted: August 11, 2026

Record last verified: 2026-04

Locations

US (18)