Clinical Trials /

A Study of Cobimetinib Plus Atezolizumab Versus Pembrolizumab in Participants With Previously Untreated Advanced BRAFv600 Wild-Type Melanoma

NCT03273153

Description:

This is a Phase III, multicenter, open-label, randomized study designed to evaluate the efficacy, safety, and pharmacokinetics of cobimetinib plus atezolizumab compared with pembrolizumab in treatment-naive participants with advanced BRAFV600 wild-type melanoma.

Related Conditions:
  • Melanoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: A Study of Cobimetinib Plus Atezolizumab Versus Pembrolizumab in Participants With Previously Untreated Advanced BRAFv600 Wild-Type Melanoma
  • Official Title: A Phase III, Open-Label, Multicenter, Two Arm, Randomized Study to Investigate the Efficacy and Safety of Cobimetinib Plus Atezolizumab Versus Pembrolizumab in Patients With Previously Untreated Advanced BRAF V600 Wild-Type Melanoma

Clinical Trial IDs

  • ORG STUDY ID: CO39722
  • SECONDARY ID: 2016-004387-18
  • NCT ID: NCT03273153

Conditions

  • Advanced BRAFV600 Wild-type Melanoma

Interventions

DrugSynonymsArms
CobimetinibCobimetinib and Atezolizumab
AtezolizumabCobimetinib and Atezolizumab
PembrolizumabPembrolizumab

Purpose

This is a Phase III, multicenter, open-label, randomized study designed to evaluate the efficacy, safety, and pharmacokinetics of cobimetinib plus atezolizumab compared with pembrolizumab in treatment-naive participants with advanced BRAFV600 wild-type melanoma.

Trial Arms

NameTypeDescriptionInterventions
Cobimetinib and AtezolizumabExperimentalParticipants will receive 60 mg of cobimetinib orally from Days 1 to 21 along with 840 mg of atezolizumab by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle until investigator-determined disease progression, unacceptable toxicity, death, patient or physician decision to withdraw, or pregnancy, whichever occurs first. There will be no cobimetinib administration for 7 days (Days 22-28) in each cycle.
  • Cobimetinib
  • Atezolizumab
PembrolizumabActive ComparatorParticipants will receive 200 mg of pembrolizumab administered by IV infusion every 3 weeks (Q3W) until investigator-determined disease progression, unacceptable toxicity, death, patient or physician decision to withdraw, or pregnancy, whichever occurs first.
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

        Disease-Specific Inclusion Criteria

          -  Histologically confirmed Stage IV (metastatic) or unresectable Stage IIIc (locally
             advanced) melanoma

          -  Naive to prior systemic anti-cancer therapy for melanoma

          -  Documentation of BRAFV600 wild-type status in melanoma tumor tissue through use of a
             clinical mutation test approved by the local health authority

          -  A representative, formalin-fixed, paraffin-embedded (FFPE) tumor specimen in a
             paraffin block (preferred) or 20 slides containing unstained, freshly cut, serial
             sections must be submitted along with an associated pathology report prior to study
             entry. If 20 slides are not available or the tissue block is not of sufficient size,
             the patient may still be eligible for the study, after discussion with and approval by
             the Medical Monitor

          -  Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST)
             v1.1

          -  Age >=18 years at time of signing Informed Consent Form

          -  Ability to comply with the study protocol, in the investigator's judgment

          -  Histologically or cytologically confirmed BRAFV600 wild-type melanoma

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

          -  Life expectancy >=3 months

          -  Adequate hematologic and end-organ function

          -  For women of childbearing potential: agreement to remain abstinent or use at least two
             forms of effective contraceptive with a failure rate of < 1% per year during the
             treatment period and for at least 3 months after the last dose of cobimetinib and at
             least 5 months after the last dose of atezolizumab or pembrolizumab

          -  For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use
             contraceptive measures (e.g. condom), and agreement to refrain from donating sperm,
             for at least 3 months after the last dose of cobimetinib

          -  Willingness and ability of participants to use an electronic device to report selected
             study outcomes

        Exclusion Criteria:

        General Exclusion Criteria

          -  Inability to swallow medications

          -  Malabsorption condition that would alter the absorption of orally administered
             medications

          -  Pregnancy, breastfeeding, or intention of becoming pregnant during the study

          -  History of severe hypersensitivity reactions to components of the cobimetinib,
             atezolizumab, or pembrolizumab formulations

          -  Current or recent treatment with therapeutic antibiotics, live attenuated vaccines or
             systemic immunostimulatory/immunosuppresive medication

          -  Any serious medical condition or abnormality in clinical laboratory tests that, in the
             investigator's judgment, precludes the patient's safe participation in and completion
             of the study Cancer-Related Exclusion Criteria

          -  Ocular melanoma

          -  Major surgery or radiotherapy within 21 days prior to Day 1 of Cycle 1 or anticipation
             of needing such procedure while receiving study treatment

          -  Uncontrolled tumor-related pain

          -  Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated
             drainage more than once every 28 days

          -  Active or untreated central nervous system (CNS) metastases Exclusions Related to
             Cardiovascular Disease

          -  Unstable angina, new-onset angina within last 3 months, myocardial infarction within
             the last 6 months prior to Day 1 of Cycle 1, or current congestive heart failure
             classified as New York Heart Association Class II or higher

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

          -  Poorly controlled hypertension, defined as sustained, uncontrolled, non-episodic
             baseline hypertension consistently above 159/99 mmHg despite optimal medical
             management

          -  History or presence of an abnormal electrocardiogram (ECG) that is clinically
             significant in the investigator's opinion, including complete left bundle branch
             block, second- or third degree heart block, or evidence of prior myocardial infarction
             Exclusions Related to Infections

          -  HIV infection

          -  Active tuberculosis infection

          -  Severe infections within 4 weeks prior to Day 1 of Cycle 1, including, but not limited
             to, hospitalization for complications of infection, bacteremia, or severe pneumonia

          -  Signs or symptoms of clinically relevant infection within 2 weeks prior to Day 1 of
             Cycle 1

          -  Treatment with oral or IV antibiotics within 2 weeks prior to Day 1 of Cycle 1

          -  Active or chronic viral hepatitis B or C infection Exclusions Related to Ocular
             Disease

          -  Known risk factors for ocular toxicity Exclusions Related to Autoimmune Conditions and
             Immunomodulatory Drugs

          -  Active or history of autoimmune disease or immune deficiency

          -  Prior allogeneic stem cell or solid organ transplantation

          -  History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced or
             idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan

          -  Treatment with systemic immunosuppressive medications within 2 weeks prior to Day 1,
             Cycle 1 Exclusions Related to Other Medical Conditions or Medications

          -  Active malignancy (other than melanoma) or a prior malignancy within the past 3 years

          -  Any Grade >=3 hemorrhage or bleeding event within 28 days of Day 1 of Cycle 1

          -  History of stroke, reversible ischemic neurological defect, or transient ischemic
             attack within 6 months prior to Day 1

          -  Proteinuria >3.5 gm/24 hr

          -  Consumption of foods, supplements, or drugs that are strong or moderate CYP3A4 enzyme
             inducers or inhibitors at least 7 days prior to Day 1 of Cycle 1 and during study
             treatment
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival (PFS) as Determined by the Independent Review Committee (IRC)
Time Frame:Up to 7 years
Safety Issue:
Description:PFS is defined as the time from randomization to the first occurrence of disease progression, as determined by an IRC according to RECIST v1.1, or death from any cause, whichever occurs first. Progressive disease (PD) for target lesion: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of >/=5 mm. PD for non-target lesion: Unequivocal progression of existing non-target lesions.

Secondary Outcome Measures

Measure:PFS as Determined by the Investigator
Time Frame:Up to 7 years
Safety Issue:
Description:PFS is defined as the time from randomization to the first occurrence of disease progression, as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurs first. Progressive disease (PD) for target lesion: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of >/=5 mm. PD for non-target lesion: Unequivocal progression of existing non-target lesions.
Measure:Objective Response Rate
Time Frame:Up to 7 years
Safety Issue:
Description:Objective response rate is defined as the percentage of participants with a complete response (CR) or a partial response (PR) on two consecutive occasions >/=4 weeks apart, as determined by the investigator through the use of RECIST v1.1. For target lesion, CR: the disappearance of all target lesions, any pathological lymph nodes must have a reduction in short axis to <10 mm. PR: at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. For non-target lesion, CR: the disappearance of all non-target lesions and (if applicable) normalization of tumor marker level, all lymph nodes must be non-pathological in size (<10 mm short axis).
Measure:Disease Control Rate (DCR)
Time Frame:Up to 7 years
Safety Issue:
Description:DCR is defined as the proportion of participants with a complete response, a partial response, or stable disease at 16 weeks. For target lesion, CR: the disappearance of all target lesions, any pathological lymph nodes must have a reduction in short axis to <10 mm. PR: at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. For non-target lesion, CR: the disappearance of all non-target lesions and (if applicable) normalization of tumor marker level, all lymph nodes must be non-pathological in size (<10 mm short axis). Stable disease (SD): neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD.
Measure:Overall Survival (OS)
Time Frame:Up to 7 years
Safety Issue:
Description:OS is defined as the time from randomization to death from any cause.
Measure:Duration of Objective Response
Time Frame:Up to 7 years
Safety Issue:
Description:Duration of objective response is defined as the time from the first occurrence of a documented objective response to disease progression, as determined by the investigator through use of RECIST v1.1, or death from any cause, whichever occurs first.
Measure:Two-year Landmark Survival
Time Frame:At 2 years
Safety Issue:
Description:Two-year landmark survival is defined as survival at 2 years.
Measure:Change From Baseline in Health-related Quality of Life (HRQoL) Scores
Time Frame:Up to 7 years
Safety Issue:
Description:HRQoL scores are assessed through global health status (GHS)/ quality of life (QoL) subscale of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ C30). These are based on questions 29 and 30 of the EORTC QLQ-C30. These questions on global health status/QoL scale are coded on 7-point scale (1=very poor to 7=excellent). Raw scores will be linearly transformed to obtain the score ranging from 0 to 100, where higher score represents a higher ("better") level of functioning.
Measure:Number of Participants with Adverse Events (AEs)
Time Frame:Up to 7 years
Safety Issue:
Description:An adverse event is any untoward medical occurrence in a patient administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Measure:Number of Participants With Abnormal Vital Signs
Time Frame:Up to 7 years
Safety Issue:
Description:Vital signs will include temperature pulse rate, respiratory rate, and systolic and diastolic blood pressure.
Measure:Number of Participants With Laboratory Abnormalities
Time Frame:Up to 7 years
Safety Issue:
Description:Participants with laboratory abnormalities will be reported.
Measure:Plasma Concentration of Cobimetinib
Time Frame:Days 1 and 15 of Cycle 1
Safety Issue:
Description:Plasma concentration of cobimetinib at specified time points will be reported.
Measure:Serum Concentration of Atezolizumab
Time Frame:Day 1 of Cycle 1, 2, 3 and 30 days after treatment discontinuation
Safety Issue:
Description:Serum concentration of atezolizumab at specified time points will be reported.
Measure:Percentage of Participants with Anti-drug Antibodies (ADAs)
Time Frame:Day 1 of Cycle 1, 2, 3 and 30 days after treatment discontinuation
Safety Issue:
Description:Participants with ADAs during the study relative to the prevalence of ADAs at baseline will be reported.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Hoffmann-La Roche

Last Updated

October 17, 2017