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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03178851




Registration number
NCT03178851
Ethics application status
Date submitted
1/06/2017
Date registered
7/06/2017
Date last updated
11/07/2019

Titles & IDs
Public title
Cobimetinib (Targeted Therapy) Plus Atezolizumab (Immunotherapy) in Participants With Advanced Melanoma Whose Cancer Has Worsened During or After Treatment With Previous Immunotherapy and Atezolizumab Monotherapy in Participants With Previously Untreated Advanced Melanoma
Scientific title
A Phase Ib Study Evaluating Cobimetinib Plus Atezolizumab in Patients With Advanced BRAF V600 Wild-Type Melanoma Who Have Progressed During or After Treatment With Anti-PD-1 Therapy and Atezolizumab Monotherapy in Patients With Previously Untreated Advanced BRAF V600 Wild-Type Melanoma
Secondary ID [1] 0 0
2016-004402-34
Secondary ID [2] 0 0
CO39721
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Malignant Melanoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma

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

Experimental: Cohort A - Participants with disease progression on or after treatment with an anti-PD-1 agent will receive cobimetinib and atezolizumab treatment during 28-day cycles.

Experimental: Cohort B - Participants with disease progression on or after treatment with an anti-PD-1 agent will receive cobimetinib prior to initiating atezolizumab treatment during Cycle 1. During subsequent 28-day cycles participants will initiate both atezolizumab and cobimetinib on Day 1 of each cycle. Participants in this cohort will undergo tumor biopsies before and during treatment.

Experimental: Cohort C - Participants with advanced melanoma, who have not received previous treatment, will receive atezolizumab monotherapy during 21-day cycles.


Other interventions: Atezolizumab
Atezolizumab, 840 mg intravenously every two weeks (Q2W) on Days 1 and 15 of each 28-day cycle, until loss of clinical benefit

Treatment: Drugs: Cobimetinib
Cobimetinib, 60 mg orally once daily (QD) on Days 1-21 of each 28-day cycle, until loss of clinical benefit

Other interventions: Atezolizumab
Atezolizumab, 840 mg intravenously on Day 15 of Cycle 1; thereafter Q2W on Days 1 and 15 of Cycle 2 and all subsequent 28-day cycles, until loss of clinical benefit

Other interventions: Atezolizumab
Atezolizumab, 1200 mg intravenously every three weeks (Q3W) on Day 1 of each 21-day cycle, until loss of clinical benefit

Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Objective Response Rate (ORR) - ORR is defined as the percentage of participants with confirmed objective response (OR). Confirmed OR is defined as complete response (CR) or partial response (PR) on two consecutive occasions = 4 weeks apart, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR is defined as disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
Timepoint [1] 0 0
Up to approximately 2 years
Primary outcome [2] 0 0
Disease Control Rate (DCR) - DCR is defined as the percentage of participants with CR, PR, or stable disease (SD) at 16 weeks. Per RECIST v1.1, CR is defined as disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression, taking as reference the smallest sum on study. Disease progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including baseline, or the appearance of one or more new lesions.
Timepoint [2] 0 0
Week 16
Secondary outcome [1] 0 0
Duration of Response (DOR) - DOR is defined as the time from the first occurrence of documented OR to disease progression, as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurs first. Disease progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including baseline; or the appearance of one or more new lesions.
Timepoint [1] 0 0
Up to approximately 2 years
Secondary outcome [2] 0 0
Overall Survival (OS) - OS is defined as the time from Cycle 1, Day 1 to death from any cause.
Timepoint [2] 0 0
Up to approximately 2 years
Secondary outcome [3] 0 0
Progression-Free Survival (PFS) - PFS is defined as the time from Cycle 1, Day 1 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. Disease progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including baseline; or the appearance of one or more new lesions.
Timepoint [3] 0 0
Up to approximately 2 years
Secondary outcome [4] 0 0
Clearance of Atezolizumab - Clearance is the process of drug elimination from the body.
Timepoint [4] 0 0
Cohort A: Cycle 1, Day 1 - pre-dose, 30 minutes (min) post-dose. Cohort B: Cycle 1, Day 15 - pre-dose, 30 min post-dose. Cohorts A and B: Cycles 2, 3, 4, 8, 12, and 16 - pre-dose, discontinuation, 120 days after last dose. Each cycle is 28 days.
Secondary outcome [5] 0 0
Clearance of Cobimetinib - Clearance is the process of drug elimination from the body.
Timepoint [5] 0 0
Cohort A: Cycle 1, Day 1 - 2-4 hours (hr) post-dose, Cycle 1, Day 15 - pre-dose, 2-4 hr post-dose. Cohort B: Cycle 1, Day 15 - pre-dose, 2-4 hr post-dose. Each cycle is 28 days.
Secondary outcome [6] 0 0
Percentage of Participants with Adverse Events - An adverse event is any untoward medical occurrence in a participant 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 [6] 0 0
Up to approximately 2 years
Secondary outcome [7] 0 0
Change from Baseline in Percentage of Participants with Anti-drug Antibodies (ADAs) to Atezolizumab - To evaluate the immune response to atezolizumab the percentage of participants with ADAs to atezolizumab will be determined at baseline and during the study.
Timepoint [7] 0 0
Cohorts A and C: Cycle 1, Day 1 pre-dose. Cohort B: Cycle 1, Day 15 pre-dose. Cohorts A, B and C: Cycles, 2, 3, 4, 8, 12, and 16 pre-dose, discontinuation, 120 days after last dose. Cohorts A and B: each cycle is 28 days. Cohort C: each cycle is 21 days.
Secondary outcome [8] 0 0
Cohort C: Objective Response Rate (ORR) - ORR is defined as the percentage of participants with confirmed objective response (OR), as determined by an independent review committee (IRC) according to RECIST v1.1. Confirmed OR is defined as complete response (CR) or partial response (PR) on two consecutive occasions = 4 weeks apart, as determined by an independent review committee (IRC) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR is defined as disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
Timepoint [8] 0 0
Up to approximately 4 years
Secondary outcome [9] 0 0
Cohort C: Disease Control Rate (DCR) - DCR is defined as the percentage of participants with CR, PR, or stable disease (SD), as determined by an independent review committee (IRC) according to RECIST v1.1. CR is defined as disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression, taking as reference the smallest sum on study. Disease progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including baseline, or the appearance of one or more new lesions.
Timepoint [9] 0 0
Up to approximately 4 years
Secondary outcome [10] 0 0
Cohort C: Duration of Response (DOR) - DOR is defined as the time from the first occurrence of documented OR to disease progression, as determined by an independent review committee (IRC) according to RECIST v1.1, or death from any cause, whichever occurs first. Disease progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including baseline; or the appearance of one or more new lesions.
Timepoint [10] 0 0
Up to approximately 4 years
Secondary outcome [11] 0 0
Cohort C: Progression-free Survival (PFS) - PFS is defined as the time from Cycle 1, Day 1 to the first occurrence of disease progression, as determined by an independent review committee (IRC) according to RECIST v1.1, or death from any cause, whichever occurs first. Disease progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including baseline; or the appearance of one or more new lesions.
Timepoint [11] 0 0
Up to approximately 4 years

Eligibility
Key inclusion criteria
Inclusion criteria

Disease-Specific Cohorts A and B:

- Histologically confirmed Stage IV (metastatic) or unresectable Stage IIIc BRAF V600 WT
(locally advanced) melanoma

- Documentation of BRAF V600 mutation-negative status in melanoma tumor tissue (archival
[< 5 years old] or newly obtained) through use of a clinical mutation test approved by
the local health authority

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

- Disease progression on or after treatment with a programmed death (PD)-1 inhibitor
either as monotherapy or in combination with other agent(s)

Additional Disease-Specific Inclusion Criteria in Cohort B (Biopsy Cohort):

- Progressed on or after anti-PD-1 therapy within 12 weeks before study start

- Received a minimum of two cycles of anti-PD-1 therapy

- Meet the following criteria for resistance to an anti-PD-1 agent: primary resistance
defined as disease progression, according to RECIST v1.1, as best response; secondary
resistance defined as disease progression after initial confirmed response according
to RECIST v1.1

- Consent to undergo tumor biopsies of accessible lesions, before and during treatment
and at radiographic progression, for biomarker analyses.

- Have at least two accessible lesions that are amenable to excisional or core-needle
(minimum three cores and minimum diameter 18 gauge; however, 16 gauge is desirable)
biopsy without unacceptable risk of a major procedural complication. Exceptions may be
made if patient has only one lesion that allows multiple biopsies.

Disease-Specific Cohort C:

- Histologically confirmed Stage IV (metastatic) or unresectable Stage IIIc BRAFV600-WT
(locally advanced) melanoma

- Naive to prior systemic anti-cancer therapy for melanoma

- Documentation of BRAFV600 mutation-negative status in melanoma tumor tissue (archival
[< 5 years old] or newly obtained) 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.

- Measurable disease according to RECIST v1.1.

General

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

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

- Available and adequate baseline tumor tissue sample

- Life expectancy = 18 weeks

- Adequate hematologic and end-organ function, defined by laboratory test results,
obtained within 14 days before initiation of study treatment

- For women of childbearing potential: abstinent or use an effective form of
contraceptive method for at least 3 months for cobimetinib and at least 5 months for
atezolizumab. Women must refrain from donating eggs during this same period.

- For men: abstinent or use contraceptive measures and agreement to refrain from
donating sperm for at least 3 months after cobimetinib and atezolizumab
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria

- Prior treatment with a mitogen activated-protein kinase (MAPK) inhibitor

- Ocular melanoma

- Major surgical procedure other than for diagnosis within 4 weeks before initiation of
study treatment, or anticipation of need for a major surgical procedure during the
course of the study

- Traumatic injury within 2 weeks before initiation of study treatment

- Palliative radiotherapy within 14 days before initiation of study treatment

- Active malignancy (other than BRAF V600 mutation-negative melanoma) or malignancy
within 3 years

- Treatment with any anti-cancer agent 14 days prior to Cycle, Day 1 other than aPD-1
based therapy

- Adverse events from prior anti-cancer therapy that have not resolved to Grade = 1.
Clinically stable patients with manageable immune-related adverse events resulting
from prior cancer immunotherapy may be eligible for the study.

- For Cohort C only: any prior anti-cancer therapy for advanced melanoma

- History or evidence of ongoing serous retinopathy or retinal vein occlusion (RVO) at
baseline

- History of clinically significant cardiac dysfunction

- Active or untreated central nervous system (CNS) metastases

- History of metastases to brain stem, midbrain, pons, or medulla, or within 10
millimeter (mm) of the optic apparatus (optic nerves and chiasm)

- History of leptomeningeal metastatic disease

- Human immunodeficiency virus (HIV) infection

- Active tuberculosis

- Severe infection within 4 weeks before initiation of study treatment

- Signs or symptoms of infection within 2 weeks before initiation of study treatment

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

- Active or chronic viral hepatitis B or C infection

- Active or history of autoimmune disease or immune deficiency

- Prior allogeneic stem cell or solid organ transplantation

- History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis
obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of
active pneumonitis on screening chest computed tomography (CT) scan

- Treatment with systemic immunosuppressive medications with the following exceptions:

- Patients who have received acute, low-dose systemic immunosuppressant medication (= 10
mg/day oral prednisone or equivalent) or a one-time pulse dose of systemic
immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast
allergy) are eligible for the study after Medical Monitor approval has been obtained.

- Patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for
chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids
for orthostatic hypotension or adrenal insufficiency are eligible for the study.

- Current severe, uncontrolled systemic disease other than cancer

- 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

- Anticipated use of any concomitant medication during or within 7 days before
initiation of study treatment that is known to cause QT prolongation

- Any psychological, familial, sociological, or geographic condition that may hamper
compliance with the protocol and follow-up after treatment discontinuation

- History of malabsorption or other clinically significant metabolic dysfunction that
may interfere with absorption of oral study treatment

- Pregnant or breastfeeding, or intending to become pregnant during the study

- Known clinically significant liver disease

- Any other disease, metabolic dysfunction, physical examination finding, or clinical
laboratory finding that contraindicates the use of an investigational drug, may affect
the interpretation of the results, or may render the participant at high risk for
treatment complications

- Treatment with a live, attenuated vaccine within 4 weeks before initiation of study
treatment, or anticipation of need for such a vaccine during the course of the study

- Known hypersensitivity to any component of the atezolizumab or cobimetinib
formulations

- History of severe allergic, anaphylactic, or other hypersensitivity reactions to
chimeric or humanized antibodies or fusion proteins

- Treatment with any other investigational agent or participation in another clinical
study with therapeutic intent

- Inability or unwillingness to swallow pills

- Requirement for concomitant therapy or food that is prohibited during the study

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised 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 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
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)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
Blacktown Hospital - Blacktown
Recruitment hospital [2] 0 0
Melanoma Institute Australia - North Sydney
Recruitment hospital [3] 0 0
Mid North Coast Cancer Institute - Port Macquarie
Recruitment hospital [4] 0 0
Greenslopes Private Hospital; Clinic Pharmacy - Greenslopes
Recruitment hospital [5] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [6] 0 0
Peter Maccallum Cancer Centre - Melbourne
Recruitment hospital [7] 0 0
Alfred Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
0002148 - Blacktown
Recruitment postcode(s) [2] 0 0
2060 - North Sydney
Recruitment postcode(s) [3] 0 0
2444 - Port Macquarie
Recruitment postcode(s) [4] 0 0
4120 - Greenslopes
Recruitment postcode(s) [5] 0 0
5042 - Bedford Park
Recruitment postcode(s) [6] 0 0
3000 - Melbourne
Recruitment postcode(s) [7] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Michigan
Country [5] 0 0
United States of America
State/province [5] 0 0
Missouri
Country [6] 0 0
United States of America
State/province [6] 0 0
Tennessee
Country [7] 0 0
United States of America
State/province [7] 0 0
Texas
Country [8] 0 0
Bosnia and Herzegovina
State/province [8] 0 0
Banja Luka
Country [9] 0 0
Bosnia and Herzegovina
State/province [9] 0 0
Sarajevo
Country [10] 0 0
Bosnia and Herzegovina
State/province [10] 0 0
Tuzla
Country [11] 0 0
Brazil
State/province [11] 0 0
CE
Country [12] 0 0
Brazil
State/province [12] 0 0
MG
Country [13] 0 0
Brazil
State/province [13] 0 0
RJ
Country [14] 0 0
Brazil
State/province [14] 0 0
RS
Country [15] 0 0
Brazil
State/province [15] 0 0
SP
Country [16] 0 0
Korea, Republic of
State/province [16] 0 0
Seoul
Country [17] 0 0
Poland
State/province [17] 0 0
Gdansk
Country [18] 0 0
Poland
State/province [18] 0 0
Poznan
Country [19] 0 0
Poland
State/province [19] 0 0
Warszawa
Country [20] 0 0
South Africa
State/province [20] 0 0
Cape Town
Country [21] 0 0
South Africa
State/province [21] 0 0
Centurion
Country [22] 0 0
South Africa
State/province [22] 0 0
George
Country [23] 0 0
South Africa
State/province [23] 0 0
Johannesburg
Country [24] 0 0
South Africa
State/province [24] 0 0
Port Elizabeth
Country [25] 0 0
South Africa
State/province [25] 0 0
Pretoria
Country [26] 0 0
Spain
State/province [26] 0 0
LA Coruña
Country [27] 0 0
Spain
State/province [27] 0 0
Navarra
Country [28] 0 0
Spain
State/province [28] 0 0
Sevilla
Country [29] 0 0
Spain
State/province [29] 0 0
Barcelona
Country [30] 0 0
Spain
State/province [30] 0 0
Madrid
Country [31] 0 0
Ukraine
State/province [31] 0 0
Chernihiv Governorate
Country [32] 0 0
Ukraine
State/province [32] 0 0
Dnipropetrovsk
Country [33] 0 0
Ukraine
State/province [33] 0 0
Kiev
Country [34] 0 0
Ukraine
State/province [34] 0 0
Lviv
Country [35] 0 0
Ukraine
State/province [35] 0 0
Sumy

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

Ethics approval
Ethics application status

Summary
Brief summary
This study will evaluate the preliminary efficacy, safety, and pharmacokinetics of
cobimetinib and atezolizumab in participants with advanced BRAF V600-wild type (WT),
metastatic, or unresectable locally advanced melanoma who have progressed on prior anti-PD-1
therapy. In addition, this study will evaluate the efficacy, safety, and pharmacokinetics of
atezolizumab monotherapy in participants with BRAFV600-WT metastatic or unresectable locally
advanced melanoma, who have not been previously treated.
Trial website
https://clinicaltrials.gov/show/NCT03178851
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
Reference Study ID Number: CO39721 www.roche.com/about_roche/roche_worldwide.htm
Address 0 0
Country 0 0
Phone 0 0
888-662-6728 (U.S. only)
Fax 0 0
Email 0 0
global-roche-genentech-trials@gene.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03178851