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A Study to Investigate the Efficacy and Safety of Cobimetinib Plus Atezolizumab in Participants With Solid Tumors

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03264066
Recruitment Status : Active, not recruiting
First Posted : August 28, 2017
Last Update Posted : November 5, 2019
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief Summary:
This is a study to evaluate the efficacy, safety, and pharmacokinetics of cobimetinib plus atezolizumab in participants with advanced solid tumors including the following cohorts: squamous cell carcinoma of the head and neck (SCCHN), urothelial carcinoma (UC), and renal cell carcinoma (RCC).

Condition or disease Intervention/treatment Phase
Solid Tumors Drug: Cobimetinib Drug: Atezolizumab Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 88 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II, Open-Label, Multicenter, Multicohort Study to Investigate the Efficacy and Safety of Cobimetinib Plus Atezolizumab in Patients With Solid Tumors
Actual Study Start Date : November 23, 2017
Actual Primary Completion Date : September 5, 2019
Estimated Study Completion Date : January 26, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Cohort 3 - RCC - treatment naive
In participants with metastatic RCC who are anti-PD-1 and anti-PD-L1 treatment naive, cobimetinib will be administered at the approved dose and schedule of 60 milligrams (mg) once daily (QD) for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.
Drug: Cobimetinib
Participants will receive cobimetinib 60 mg (3 tablets of 20 mg each) orally once a day on Days 1−21 of each 28-day cycle.
Other Name: Cotellic

Drug: Atezolizumab

Atezolizumab will be given at a fixed dose of 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.

Only for participants in cohort 7, the first dose of atezolizumab of 840 mg by IV infusions on Day 15 of Cycle 1; thereafter, they will receive atezolizumab 840 mg IV infusion Q2W on Days 1 and 15 of Cycle 2 and all subsequent cycles

Other Name: Tecentriq

Experimental: Cohort 1 - SCCHN - treatment naive
In participants with recurrent or advanced / metastatic SSCHN who are anti-PD-1 and anti-PD-L1 treatment naive, cobimetinib will be administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.
Drug: Cobimetinib
Participants will receive cobimetinib 60 mg (3 tablets of 20 mg each) orally once a day on Days 1−21 of each 28-day cycle.
Other Name: Cotellic

Drug: Atezolizumab

Atezolizumab will be given at a fixed dose of 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.

Only for participants in cohort 7, the first dose of atezolizumab of 840 mg by IV infusions on Day 15 of Cycle 1; thereafter, they will receive atezolizumab 840 mg IV infusion Q2W on Days 1 and 15 of Cycle 2 and all subsequent cycles

Other Name: Tecentriq

Experimental: Cohort 2 - UC - treatment naive
In participants with advanced / metastatic UC who are anti-PD-1 and anti-PD-L1 treatment naive, cobimetinib will be administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.
Drug: Cobimetinib
Participants will receive cobimetinib 60 mg (3 tablets of 20 mg each) orally once a day on Days 1−21 of each 28-day cycle.
Other Name: Cotellic

Drug: Atezolizumab

Atezolizumab will be given at a fixed dose of 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.

Only for participants in cohort 7, the first dose of atezolizumab of 840 mg by IV infusions on Day 15 of Cycle 1; thereafter, they will receive atezolizumab 840 mg IV infusion Q2W on Days 1 and 15 of Cycle 2 and all subsequent cycles

Other Name: Tecentriq

Experimental: Cohort 4 - SCCHN - previous treatment exposure
In participants with SCCHN whose disease has progressed while receiving anti-PD-1 or anti-PD-L1 therapy, cobimetinib will be administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.
Drug: Cobimetinib
Participants will receive cobimetinib 60 mg (3 tablets of 20 mg each) orally once a day on Days 1−21 of each 28-day cycle.
Other Name: Cotellic

Drug: Atezolizumab

Atezolizumab will be given at a fixed dose of 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.

Only for participants in cohort 7, the first dose of atezolizumab of 840 mg by IV infusions on Day 15 of Cycle 1; thereafter, they will receive atezolizumab 840 mg IV infusion Q2W on Days 1 and 15 of Cycle 2 and all subsequent cycles

Other Name: Tecentriq

Experimental: Cohort 5 - UC - previous treatment exposure
In participants with UC whose disease has progressed while receiving anti-PD-1 or anti-PD-L1 therapy, cobimetinib will be administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.
Drug: Cobimetinib
Participants will receive cobimetinib 60 mg (3 tablets of 20 mg each) orally once a day on Days 1−21 of each 28-day cycle.
Other Name: Cotellic

Drug: Atezolizumab

Atezolizumab will be given at a fixed dose of 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.

Only for participants in cohort 7, the first dose of atezolizumab of 840 mg by IV infusions on Day 15 of Cycle 1; thereafter, they will receive atezolizumab 840 mg IV infusion Q2W on Days 1 and 15 of Cycle 2 and all subsequent cycles

Other Name: Tecentriq

Experimental: Cohort 6 - RCC - previous treatment exposure
In participants with RCC whose disease has progressed while receiving anti-PD-1 or anti-PD-L1 therapy, cobimetinib will be administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.
Drug: Cobimetinib
Participants will receive cobimetinib 60 mg (3 tablets of 20 mg each) orally once a day on Days 1−21 of each 28-day cycle.
Other Name: Cotellic

Drug: Atezolizumab

Atezolizumab will be given at a fixed dose of 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.

Only for participants in cohort 7, the first dose of atezolizumab of 840 mg by IV infusions on Day 15 of Cycle 1; thereafter, they will receive atezolizumab 840 mg IV infusion Q2W on Days 1 and 15 of Cycle 2 and all subsequent cycles

Other Name: Tecentriq

Experimental: Cohort 7 - biopsy cohort
In participants with solid non-melanoma, non- hematologic tumors who previously developed primary or secondary resistance to an anti-PD-1 or anti-PD-L1 agent, cobimetinib will be administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle. The first dose of atezolizumab of 840 mg by IV infusions on Day 15 of Cycle 1. Thereafter, they will receive atezolizumab 840 mg IV infusion Q2W on Days 1 and 15 of Cycle 2 and all subsequent cycles
Drug: Cobimetinib
Participants will receive cobimetinib 60 mg (3 tablets of 20 mg each) orally once a day on Days 1−21 of each 28-day cycle.
Other Name: Cotellic

Drug: Atezolizumab

Atezolizumab will be given at a fixed dose of 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.

Only for participants in cohort 7, the first dose of atezolizumab of 840 mg by IV infusions on Day 15 of Cycle 1; thereafter, they will receive atezolizumab 840 mg IV infusion Q2W on Days 1 and 15 of Cycle 2 and all subsequent cycles

Other Name: Tecentriq




Primary Outcome Measures :
  1. Objective Response Rate (ORR) [ Time Frame: Up to 3 years ]
    Objective response is defined as a complete response (CR) or a partial response (PR) on two consecutive tumor assessments ≥4 weeks apart, as determined by the investigators using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1). CR is defined as disappearance of all lesions. PR is defined as ≥30% decrease in tumor burden, in the absence of CR.


Secondary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: Up to 3 years ]
    Overall survival is defined as the time from enrollment to death from any cause.

  2. Progression-Free Survival (PFS) [ Time Frame: Up to 3 years ]
    PFS is defined as the time from enrollment to the first occurrence of disease progression as determined by the investigator(s), using RECIST v1.1, or to death from any cause, whichever occurs first. Disease progression is defined as ≥20% increase in tumor burden.

  3. Duration of Response (DOR) [ Time Frame: Up to 3 years ]
    DOR is defined as the time from the first occurrence of a documented, confirmed objective response to disease progression as determined by the investigator, using RECIST v1.1, or to death from any cause, whichever occurs first. Objective response is defined as a complete response (CR) or a partial response (PR) on two consecutive tumor assessments ≥4 weeks apart. CR is defined as disappearance of all lesions. PR is defined as ≥30% decrease in tumor burden, in the absence of CR. Disease progression is defined as ≥20% increase in tumor burden.

  4. Disease Control Rate (DCR) [ Time Frame: Up to 3 years ]
    DCR is defined as the percentage of participants with a complete response (CR), a partial response (PR), or stable disease at 16 weeks as determined by the investigator using RECIST v1.1. CR is defined as disappearance of all lesions. PR is defined as ≥30% decrease in tumor burden, in the absence of CR. Stable disease is defined as neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for disease progression. Disease progression is defined as ≥20% increase in tumor burden.

  5. Occurrence and Severity of Adverse Events [ Time Frame: Up to 3 years ]
    Severity will be determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0)

  6. Number of Participants With Abnormal Vital Sign Values [ Time Frame: Up to 3 years ]
  7. Number of Participants With Abnormal Clinical Laboratory Values [ Time Frame: Up to 3 years ]
  8. Maximum Plasma Concentration (Cmax) of Cobimetinib [ Time Frame: Day 15 of Cycle 3 ]
    Cmax is the maximum (or peak) concentration that a study drug achieves in the body.

  9. Minimum Plasma Concentration (Cmin) of Cobimetinib [ Time Frame: Day 15 of Cycle 3 ]
    Cmin is the minimum (or trough) concentration that a study drug achieves in the body.

  10. Maximum Serum Concentration (Cmax) of Atezolizumab [ Time Frame: Day 1 of Cycle 1; Day 1 of Cycles 2, 4, 8, 12, and 16; Day 15 of Cycle 3; at atezolizumab treatment discontinuation visit, and <90 days after last atezolizumab infusion ]
    Cmax is the maximum (or peak) concentration that a study drug achieves in the body.

  11. Minimum Serum Concentration (Cmin) of Atezolizumab [ Time Frame: Day 1 of Cycle 1; Day 1 of Cycles 2, 4, 8, 12, and 16; Day 15 of Cycle 3; at atezolizumab treatment discontinuation visit, and <90 days after last atezolizumab infusion ]
    Cmin is the minimum (or trough) concentration that a study drug achieves in the body.

  12. Presence of Anti-drug Antibodies (ADAs) During the Study Relative to the Presence of ADAs at Baseline [ Time Frame: Day 1 of Cycle 1; Day 1 of Cycles 2, 4, 8, 12, and 16; Day 15 of Cycle 3; at atezolizumab treatment discontinuation visit, and <90 days after last atezolizumab infusion ]
    Participants are considered to be ADA positive if they are missing data at baseline but develop an ADA response following study drug administration (treatment-induced ADA response), or if they are ADA positive at baseline and the titer of one or more post-baseline samples is at least 4-fold greater (i.e., ≥0.60-titer units) than the titer of the baseline sample (treatment-enhanced ADA response). Participants are considered to be ADA negative if they are missing data at baseline, have a post-baseline ADA result, and all post-baseline samples are negative, or if they are ADA positive at baseline but do not have any post-baseline samples with a titer that is at least 4-fold greater than the titer of the baseline sample (treatment unaffected).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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:

General Inclusion Criteria:

  • Age ≥18 years
  • Ability to comply with the study protocol, in the investigator's judgment
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
  • Life expectancy ≥3 months, as determined by the investigator
  • Adequate hematologic and end-organ function

Cancer-Related Inclusion Criteria:

  • Patients must have measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) scan per RECIST v1.1.
  • Availability to provide a representative tumor specimen biopsy
  • Evidence of tumor progression on or after the last treatment regimen received and within 6 months prior to study enrollment
  • For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use a non-hormonal contraceptive method with a failure rate of <1% per year during the treatment period and for at least 5 months after the last dose of atezolizumab and within 3 months after the last dose of cobimetinib
  • For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm during the treatment period and for at least 3 months after the last dose of cobimetinib

Exclusion Criteria:

General Exclusion Criteria:

  • Inability to swallow medications
  • Malabsorption condition that would alter the absorption of orally administered medications
  • Poor peripheral venous access
  • Prior treatment with cobimetinib or a MEK inhibitor
  • Prior treatment with T-cell co-stimulating or immune checkpoint blockade therapies, including anti−CTLA-4, anti−PD-1, and anti−PD-L1 therapeutic antibodies
  • Treatment with investigational therapy within 14 days prior to initiation of study treatment
  • Any anti-cancer therapy, including chemotherapy or hormonal therapy, within 2 weeks prior to initiation of study treatment
  • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
  • Known hypersensitivity to biopharmaceutical agents produced in Chinese hamster ovary cells or any component of the atezolizumab formulation, or any component of the cobimetinib formulation
  • History of serous retinopathy, retinal vein occlusion (RVO), or evidence of ongoing serous retinopathy or RVO at baseline
  • Major surgical procedure other than for diagnosis within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study
  • Uncontrolled tumor-related pain
  • Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage more than once every 28 days
  • Uncontrolled hypercalcemia (ionized calcium >1.5 millimoles per liter [mmol/L], calcium >12 milligrams per deciliter [mg/dL], or corrected calcium greater than the upper limit of normal [ULN]) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy
  • Active or untreated central nervous system (CNS) metastases
  • Pregnancy or breastfeeding, or intending to become pregnant during the study

Exclusion Criteria based on Organ Function or Medical History

Cardiovascular

Patients who meet the following cardiovascular exclusion criterion will be excluded from study entry:

  • Left ventricular ejection fraction (LVEF) below the institutional lower limit of normal or <50%, whichever is lower

Infections Patients who meet any of the following infection exclusion criteria will be excluded from study entry:

  • Positive human immunodeficiency virus (HIV) test at screening
  • Active hepatitis B virus (HBV) infection (chronic or acute)
  • Active hepatitis C virus (HCV) infection
  • Active tuberculosis
  • Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
  • Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment

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): NCT03264066


Locations
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United States, District of Columbia
Georgetown University Medical Center
Washington, District of Columbia, United States, 20007
United States, Kansas
Kansas City - Menorah Medical Center
Kansas City, Kansas, United States, 66209
United States, New York
Memorial Sloan-Kettering Cancer Center
Commack, New York, United States, 11725
Memorial Sloan Kettering - Basking Ridge
New York, New York, United States, 10065
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
United States, Tennessee
Sarah Cannon Research Institute
Nashville, Tennessee, United States, 37203
Belgium
AZ Groeninge
Kortrijk, Belgium, 8500
Germany
Universitatsklinik Heidelberg; Universitätshautklinik und Nationales Centrum für Tumorerkrankungen
Heidelberg, Germany, 69120
Universitätsklinikum Tübingen; Klinik für Urologie
Tübingen, Germany, 72076
Hungary
Orszagos Onkologiai Intezet
Budapest, Hungary, 1122
Debreceni Egyetem Klinikai Kozpont
Debrecen, Hungary, 4032
Jósa András Oktatókórház
Nyíregyháza, Hungary, 4400
Korea, Republic of
Seoul National University Hospital
Seoul, Korea, Republic of, 03080
Asan Medical Center - Oncology
Seoul, Korea, Republic of, 05505
Yonsei Cancer Center
Seoul, Korea, Republic of, 120-752
Samsung Medical Center
Seoul, Korea, Republic of, 6351
United Kingdom
Barts & London School of Med; Medical Oncology
London, United Kingdom, EC1A 7BE
Royal Marsden Hospital - Fulham
London, United Kingdom, SW3 6JJ
The Royal Marsden
London, United Kingdom, SW7 3RP
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche

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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT03264066     History of Changes
Other Study ID Numbers: WO39760
2017-000794-37 ( EudraCT Number )
First Posted: August 28, 2017    Key Record Dates
Last Update Posted: November 5, 2019
Last Verified: November 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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Neoplasms
Atezolizumab
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs