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Trial record 9 of 41 for:    GDC-0973 | Recruiting, Not yet recruiting, Available Studies

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03600701
Recruitment Status : Recruiting
First Posted : July 26, 2018
Last Update Posted : October 29, 2019
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

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 to other places in the body, has come back, or does not respond to treatment. 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 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving atezolizumab and cobimetinib may work better in treating patients with non-small cell lung cancer.

Condition or disease Intervention/treatment Phase
Recurrent Lung Non-Small Cell Carcinoma Refractory Lung Non-Small Cell Carcinoma Stage IV Lung Non-Small Cell Cancer AJCC v7 Drug: Atezolizumab Drug: Cobimetinib Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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.

EXPLORATORY OBJECTIVES:

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.

OUTLINE:

Patients receive atezolizumab intravenously (IV) over 30-60 minutes on days 1 and 15 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.

After completion of study treatment, patients are followed up for 90 days.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Study of Atezolizumab and Cobimetinib in PD-1/PD-L1 Inhibitor Resistant or Refractory Non-Small Cell Lung Cancer
Actual Study Start Date : July 20, 2018
Estimated Primary Completion Date : July 17, 2021
Estimated Study Completion Date : July 17, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Treatment (atezolizumab, cobimetinib)
Patients receive atezolizumab IV over 30-60 minutes on days 1 and 15 and cobimetinib PO QD on days 1-21. Cycles repeat every 28 days in the absence of disease progression or unaccepted toxicity.
Drug: Atezolizumab
Given IV
Other Names:
  • MPDL 3280A
  • MPDL 328OA
  • MPDL-3280A
  • MPDL3280A
  • MPDL328OA
  • RG7446
  • RO5541267
  • Tecentriq

Drug: Cobimetinib
Given PO
Other Names:
  • Cotellic
  • GDC-0973
  • MEK Inhibitor GDC-0973
  • XL518




Primary Outcome Measures :
  1. Durable response rate to therapy [ Time Frame: Up to 90 days ]
    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.


Secondary Outcome Measures :
  1. Overall response rate [ Time Frame: Up to 90 days ]
    Will be assessed using RECIST version 1.1 criteria. Will use chi-square statistics to describe and analyze results with ethnic categories and racial categories, respectively.

  2. Duration of response [ Time Frame: Up to 90 days ]
  3. Progression free survival (PFS) [ Time Frame: Time from start of treatment to time of progression or death, whichever occurs first, assessed up to 90 days ]
    Kaplan-Meier estimates will be used to describe the PFS. The association of PFS with biomarkers will be assessed using Cox regression model with model adequacy assessment.

  4. Overall survival (OS) [ Time Frame: From start of study treatment to time of death, assessed up to 90 days ]
    Kaplan-Meier estimates will be used to describe the OS. The association of survival with biomarkers will be assessed using Cox regression model with model adequacy assessment.

  5. Grade 3 and 4 toxicities [ Time Frame: Up to 90 days ]
    Will be assessed by Common Terminology Criteria for Adverse Events version 5.

  6. Biomarker analysis [ Time Frame: Up to 90 days ]
    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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have histologically or cytologically confirmed metastatic or recurrent non-small cell lung cancer; 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

    • If, and only if, cohort 1 is positive (at least 3 out of up to 24 patients experience confirmed response) and at least one response is durable (lasting at least 6 months), then cohort 2 will open; this can occur prior to full enrollment to 24 patients; absence of a mutation in KRAS (KRAS wild type) is required for patients enrolled in cohort 2; central validation is not required for enrollment
  • 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 received anti-PD-1 or anti-PD-L1 therapy with a best response of progressive disease or stable disease lasting =< 4 months; patients who achieved a partial response or a complete response or stable disease lasting > 4 months are not eligible
  • 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 computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam
  • 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
  • Patients positive for human immunodeficiency virus (HIV) are allowed on study, but HIV-positive patients must have:

    • A stable regimen of highly active anti-retroviral therapy (HAART)
    • No requirement for concurrent antibiotics or antifungal agents for the prevention of opportunistic infections
    • A CD4 count above 250 cells/mcL and an undetectable HIV viral load on standard polymerase chain reaction (PCR)-based tests

Exclusion Criteria:

  • 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) > 450 msec within 2 weeks 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, autoimmune thyroid disease, 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03600701


Locations
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United States, District of Columbia
MedStar Georgetown University Hospital Recruiting
Washington, District of Columbia, United States, 20007
Contact: Site Public Contact    202-444-2223      
Principal Investigator: Stephen V. Liu         
United States, Florida
Moffitt Cancer Center Recruiting
Tampa, Florida, United States, 33612
Contact: Site Public Contact    800-679-0775    canceranswers@moffitt.org   
Principal Investigator: Andreas N. Saltos         
United States, Georgia
Emory University Hospital Midtown Recruiting
Atlanta, Georgia, United States, 30308
Contact: Site Public Contact    888-946-7447      
Principal Investigator: Jennifer W. Carlisle         
Emory University Hospital/Winship Cancer Institute Recruiting
Atlanta, Georgia, United States, 30322
Contact: Site Public Contact    404-778-1868      
Principal Investigator: Jennifer W. Carlisle         
Emory Saint Joseph's Hospital Recruiting
Atlanta, Georgia, United States, 30342
Contact: Site Public Contact    404-851-7115      
Principal Investigator: Jennifer W. Carlisle         
United States, New Jersey
Rutgers Cancer Institute of New Jersey Recruiting
New Brunswick, New Jersey, United States, 08903
Contact: Site Public Contact    732-235-8675      
Principal Investigator: Jyoti Malhotra         
United States, Ohio
Ohio State University Comprehensive Cancer Center Recruiting
Columbus, Ohio, United States, 43210
Contact: Site Public Contact    800-293-5066    Jamesline@osumc.edu   
Principal Investigator: Gregory A. Otterson         
United States, Virginia
University of Virginia Cancer Center Recruiting
Charlottesville, Virginia, United States, 22908
Contact: Site Public Contact    434-243-6303    PAS9E@virginia.edu   
Principal Investigator: Richard D. Hall         
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Stephen V Liu JHU Sidney Kimmel Comprehensive Cancer Center LAO

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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT03600701    
Other Study ID Numbers: NCI-2017-01812
NCI-2017-01812 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
10166 ( Other Identifier: JHU Sidney Kimmel Comprehensive Cancer Center LAO )
10166 ( Other Identifier: CTEP )
UM1CA186691 ( U.S. NIH Grant/Contract )
First Posted: July 26, 2018    Key Record Dates
Last Update Posted: October 29, 2019
Last Verified: July 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Non-Small-Cell Lung
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Atezolizumab
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs