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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03273153




Registration number
NCT03273153
Ethics application status
Date submitted
1/09/2017
Date registered
6/09/2017
Date last updated
1/07/2020

Titles & IDs
Public title
A Study of Cobimetinib Plus Atezolizumab Versus Pembrolizumab in Participants With Previously Untreated Advanced BRAFv600 Wild-Type Melanoma
Scientific 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
Secondary ID [1] 0 0
2016-004387-18
Secondary ID [2] 0 0
CO39722
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced BRAFV600 Wild-type Melanoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Cobimetinib
Treatment: Drugs - Atezolizumab
Treatment: Drugs - Pembrolizumab

Experimental: 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.

Active Comparator: 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.


Treatment: Drugs: Cobimetinib
Cobimetinib 60 mg tablets orally once daily on a 21 days on, 7 days off schedule.

Treatment: Drugs: Atezolizumab
Atezolizumab 840 mg as IV infusion once in every 2 weeks.

Treatment: Drugs: Pembrolizumab
Pembrolizumab 200 mg as IV infusion once in every 3 weeks.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression Free Survival (PFS) as Determined by the Independent Review Committee (IRC) - 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.
Timepoint [1] 0 0
Every 8 weeks (wks) from Day (D) 1 of Cycle (C) 1 through approximately 16 months
Secondary outcome [1] 0 0
PFS as Determined by the Investigator - 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.
Timepoint [1] 0 0
Every 8 weeks (wks) from Day (D) 1 of Cycle (C) 1 through approximately 16 months
Secondary outcome [2] 0 0
Objective Response as Determined by the Investigator - 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).
Timepoint [2] 0 0
Every 8 weeks (wks) from Day (D) 1 of Cycle (C) 1 through approximately 16 months
Secondary outcome [3] 0 0
Objective Response as Determined by IRC - Objective response, defined as a complete response or partial response on two consecutive occasions =4 weeks apart, as determined by IRC according to RECIST v1.1
Timepoint [3] 0 0
Every 8 weeks (wks) from Day (D) 1 of Cycle (C) 1 through approximately 16 months
Secondary outcome [4] 0 0
Disease Control Rate (DCR) - 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.
Timepoint [4] 0 0
Week 16
Secondary outcome [5] 0 0
Overall Survival (OS) - OS is defined as the time from randomization to death from any cause.
Timepoint [5] 0 0
Up to 7 years
Secondary outcome [6] 0 0
Duration of Objective Response Determined by the IRC - Duration of objective response, defined as the time from the first occurrence of a documented objective response to disease progression, as determined by an IRC according to RECIST v1.1, or death from any cause, whichever occurs first.
Timepoint [6] 0 0
Every 8 weeks (wks) from Day (D) 1 of Cycle (C) 1 through approximately 16 months
Secondary outcome [7] 0 0
Duration of Objective Response Determined by the Investigator - 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.
Timepoint [7] 0 0
Every 8 weeks (wks) from Day (D) 1 of Cycle (C) 1 through approximately 16 weeks
Secondary outcome [8] 0 0
Two-year Landmark Survival - Two-year landmark survival is defined as survival at 2 years.
Timepoint [8] 0 0
At 2 years
Secondary outcome [9] 0 0
Change From Baseline in Health-related Quality of Life (HRQoL) Scores - 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.
Timepoint [9] 0 0
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.
Secondary outcome [10] 0 0
Number of Participants With Adverse Events (AEs) - 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.
Timepoint [10] 0 0
Up to approximately 16 months
Secondary outcome [11] 0 0
Number of Participants With Abnormal Vital Signs - Vital signs will include temperature pulse rate, respiratory rate, and systolic and diastolic blood pressure.
Timepoint [11] 0 0
Up to 7 years
Secondary outcome [12] 0 0
Number of Participants With Laboratory Abnormalities - Participants with laboratory abnormalities (values outside of a defined range) will be reported.
Timepoint [12] 0 0
Up to approximately 16 months
Secondary outcome [13] 0 0
Plasma Concentration of Cobimetinib - Plasma concentration of cobimetinib at specified time points will be reported.
Timepoint [13] 0 0
Days 1 and 15 of Cycle 1
Secondary outcome [14] 0 0
Serum Concentration of Atezolizumab - Serum concentration of atezolizumab at specified time points will be reported.
Timepoint [14] 0 0
Day 1 of Cycle 1, 2, 3 and 30 days after treatment discontinuation
Secondary outcome [15] 0 0
Percentage of Participants With Anti-drug Antibodies (ADAs) - Participants with ADAs during the study relative to the prevalence of ADAs at baseline will be reported.
Timepoint [15] 0 0
Day 1 of Cycle 1, 2, 3 and 30 days after treatment discontinuation

Eligibility
Key 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

- 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 patients to report selected study outcomes (e.g., GHS and
HRQoL) using an electronic device or paper backup questionnaires.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD,TAS,WA
Recruitment hospital [1] 0 0
Cairns Base Hospital - Cairns
Recruitment hospital [2] 0 0
Townsville General Hospital - Douglas
Recruitment hospital [3] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [4] 0 0
Royal Hobart Hospital - Hobart
Recruitment hospital [5] 0 0
Fiona Stanley Hospital - Murdoch
Recruitment postcode(s) [1] 0 0
4870 - Cairns
Recruitment postcode(s) [2] 0 0
4184 - Douglas
Recruitment postcode(s) [3] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [4] 0 0
7000 - Hobart
Recruitment postcode(s) [5] 0 0
6150 - Murdoch
Recruitment outside Australia
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United States of America
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Arizona
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West Virginia
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Bruxelles
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Belgium
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Kortrijk
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Leuven
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RJ
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RS
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Reims
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Rennes
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Toulouse
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Gera
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Germany
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Minden
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Lazio
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Liguria
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Lombardia
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Piemonte
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Puglia
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Toscana
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Korea, Republic of
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Breda
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Rotterdam
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LA Coruña
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LAS Palmas
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Madrid
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Sevilla
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Spain
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Valencia
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Spain
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Zaragoza
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United Kingdom
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Bristol
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Edinburgh
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United Kingdom
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Leicester
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United Kingdom
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London
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United Kingdom
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Stoke-On-Trent
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United Kingdom
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Swansea
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United Kingdom
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Truro

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT03273153
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications