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

NCT03264066

Description:

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).

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma
  • Malignant Solid Tumor
  • Renal Cell Carcinoma
  • Urothelial Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: WO39760
  • SECONDARY ID: 2017-000794-37
  • NCT ID: NCT03264066

Conditions

  • Solid Tumors

Interventions

DrugSynonymsArms
CobimetinibCohort 3 - RCC - treatment naive
AtezolizumabCohort 3 - RCC - treatment naive

Purpose

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).

Trial Arms

NameTypeDescriptionInterventions
Cohort 3 - RCC - treatment naiveExperimentalIn 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.
  • Cobimetinib
  • Atezolizumab
Cohort 1 - SCCHN - treatment naiveExperimentalIn 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.
  • Cobimetinib
  • Atezolizumab
Cohort 2 - UC - treatment naiveExperimentalIn 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.
  • Cobimetinib
  • Atezolizumab
Cohort 4 - SCCHN - previous treatment exposureExperimentalIn 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.
  • Cobimetinib
  • Atezolizumab
Cohort 5 - UC - previous treatment exposureExperimentalIn 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.
  • Cobimetinib
  • Atezolizumab
Cohort 6 - RCC - previous treatment exposureExperimentalIn 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.
  • Cobimetinib
  • Atezolizumab
Cohort 7 - biopsy cohortExperimentalIn 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
  • Cobimetinib
  • Atezolizumab

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective Response Rate (ORR)
Time Frame:Up to 3 years
Safety Issue:
Description: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

Measure:Overall Survival (OS)
Time Frame:Up to 3 years
Safety Issue:
Description:Overall survival is defined as the time from enrollment to death from any cause.
Measure:Progression-Free Survival (PFS)
Time Frame:Up to 3 years
Safety Issue:
Description: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.
Measure:Duration of Response (DOR)
Time Frame:Up to 3 years
Safety Issue:
Description: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.
Measure:Disease Control Rate (DCR)
Time Frame:Up to 3 years
Safety Issue:
Description: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.
Measure:Occurrence and Severity of Adverse Events
Time Frame:Up to 3 years
Safety Issue:
Description:Severity will be determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0)
Measure:Number of Participants With Abnormal Vital Sign Values
Time Frame:Up to 3 years
Safety Issue:
Description:
Measure:Number of Participants With Abnormal Clinical Laboratory Values
Time Frame:Up to 3 years
Safety Issue:
Description:
Measure:Maximum Plasma Concentration (Cmax) of Cobimetinib
Time Frame:Day 15 of Cycle 3
Safety Issue:
Description:Cmax is the maximum (or peak) concentration that a study drug achieves in the body.
Measure:Minimum Plasma Concentration (Cmin) of Cobimetinib
Time Frame:Day 15 of Cycle 3
Safety Issue:
Description:Cmin is the minimum (or trough) concentration that a study drug achieves in the body.
Measure: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
Safety Issue:
Description:Cmax is the maximum (or peak) concentration that a study drug achieves in the body.
Measure: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
Safety Issue:
Description:Cmin is the minimum (or trough) concentration that a study drug achieves in the body.
Measure: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
Safety Issue:
Description: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).

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Hoffmann-La Roche

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