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
Overview
- Phase
- Phase 3
- Intervention
- Cobimetinib
- Conditions
- Advanced BRAFV600 Wild-type Melanoma
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 446
- Locations
- 121
- Primary Endpoint
- Progression Free Survival (PFS) as Determined by the Independent Review Committee (IRC)
- Status
- Terminated
- Last Updated
- 3 years ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Disease-Specific Inclusion Criteria
- •Histologically confirmed locally advanced and unresectable or metastatic 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
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
Arms & Interventions
Cobimetinib and Atezolizumab
Participants 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.
Intervention: Cobimetinib
Cobimetinib and Atezolizumab
Participants 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.
Intervention: Atezolizumab
Pembrolizumab
Participants 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.
Intervention: Pembrolizumab
Outcomes
Primary Outcomes
Progression Free Survival (PFS) as Determined by the Independent Review Committee (IRC)
Time Frame: Every 8 weeks (wks) from Day (D) 1 of Cycle (C) 1 through approximately 16 months
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 Outcomes
- Serum Concentration of Atezolizumab(Day 1 of Cycles 1, 2, and 3)
- Objective Response as Determined by IRC(Every 8 weeks (wks) from Day (D) 1 of Cycle (C) 1 through approximately 16 months)
- Objective Response as Determined by the Investigator(Every 8 weeks (wks) from Day (D) 1 of Cycle (C) 1 through approximately 16 months)
- PFS as Determined by the Investigator(Every 8 weeks (wks) from Day (D) 1 of Cycle (C) 1 through approximately 16 months)
- Overall Survival (OS)(From randomization up to approximately 3 years)
- Duration of Objective Response Determined by the Investigator(Up to 3 years)
- Number of Participants With Adverse Events (AEs)(Up to approximately 16 months)
- Plasma Concentration of Cobimetinib(Days 1 and 15 of Cycle 1)
- Duration of Objective Response Determined by the IRC(Every 8 weeks (wks) from Day (D) 1 of Cycle (C) 1 through approximately 16 months)
- Two-year Landmark Survival(At 2 years)
- Change From Baseline in Health-related Quality of Life (HRQoL) Scores(Up to approximately 16 months. Follow up is reported at weeks after participant treatment discontinuation, which could occur at any time during the study. Total time frame does not exceed 16 months.)
- Disease Control Rate (DCR)(Week 16)
- Number of Participants With Abnormal Vital Signs(From baseline up to approximately 3 years)
- Number of Participants With Laboratory Abnormalities(Up to approximately 16 months)
- Percentage of Participants With Anti-drug Antibodies (ADAs)(Day 1 of Cycle 1, 2, 3 and 30 days after treatment discontinuation)