Malignant MelanomaPhase 1NCT03178851
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
A Phase 1 study testing Atezolizumab and Cobimetinib in people with Malignant Melanoma, run by Hoffmann-La Roche at 43 sites in 7 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Melanoma
- What is being tested?
- Atezolizumab and Cobimetinib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 155 participants
- Where
- 43 sitesin 7 countries
- Study dates
- 20 Jun 2017to 21 Sep 2020
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Disease-Specific Inclusion Criteria: 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):
Show all 25Show fewer
- 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 Inclusion Criteria: 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 Inclusion Criteria:
- 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
Who cannot join
- 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
Show all 41Show fewer
- 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
Trial locations and contacts
43 sites in 7 countries.
43 sites in 7 countries
Spain9 sites
Hospital Universitari Quiron Dexeus
Barcelona, 08028
Hospital Clinic I Provincial
Barcelona, 08036
MD Anderson Cancer Center
Madrid, 28033
Hospital Universitario Ramón y Cajal; Pharmacy
Madrid, 28034
Hospital Universitario 12 de Octubre; Servicio de Oncologia
Madrid, 28041
Hospital Universitario La Paz; Servicio de Oncologia
Madrid, 28046
Clínica Universidad de Navarra
Pamplona, Navarre, 31620
Hospital Clinico Universitario de Santiago
Santiago de Compostela, LA Coruña, 15706
Hospital Universitario Virgen Macarena
Seville, Sevilla, 41071
Australia7 sites
Flinders Medical Centre
Bedford Park, South Australia, 5042
Blacktown Hospital
Blacktown, New South Wales, 2148
Greenslopes Private Hospital; Clinic Pharmacy
Greenslopes, Queensland, 4120
Peter Maccallum Cancer Centre
Melbourne, Victoria, 3000
Alfred Hospital
Melbourne, Victoria, 3004
Melanoma Institute Australia
North Sydney, New South Wales, 2060
Mid North Coast Cancer Institute
Port Macquarie, New South Wales, 2444
Brazil7 sites
Cenantron - Centro Avancado de Tratamento Oncologico
Belo Horizonte, Minas Gerais, 30130-090
Instituto de Ensino e Pesquisa Clinica do Ceara
Fortaleza, Ceará, 60130-241
Hospital Amaral Carvalho
Jaú, São Paulo, 17210-120
Hospital Sao Vicente de Paulo
Passo Fundo, Rio Grande do Sul, 99010-090
Hospital das Clinicas - UFRGS
Porto Alegre, Rio Grande do Sul, 90035-903
Hospital Sao Lucas - PUCRS
Porto Alegre, Rio Grande do Sul, 90610-000
Instituto Nacional de Cancer - INCa; Oncologia
Rio de Janeiro, Rio de Janeiro, 20560-120
South Africa7 sites
Cape Town Oncology Trials
Cape Town, 7570
GVI Constantiaberg
Cape Town, 7800
Johese Clinical Research
Centurion, 1692
Cancercare
George, 6529
Wits Clinical Research; Charlotte Maxeke Johannesburg Academic Hospital
Johannesburg, 2193
Cancercare
Port Elizabeth, 6045
Steve Biko Academic Hospital; Oncology
Pretoria, 0002
United States6 sites
University of Colorado Hospital - Anschutz Cancer Pavilion
Aurora, Colorado, 80045
Baylor University Medical Center
Dallas, Texas, 75231
Karmanos Cancer Institute
Detroit, Michigan, 48201
Sarah Cannon Research Institute
Nashville, Tennessee, 37203
HonorHealth Research Institute - Bisgrove
Scottsdale, Arizona, 85258
Washington University School of Medicine
St Louis, Missouri, 63110
Ukraine5 sites
Public Institution: City Multispecialty Clinical Hospital #4 under Dnipropetrovsk Regional Council
Dnipropetrovsk, 49102
National Cancer Institute MOH of Ukraine
Kiev, 36022
Lviv State Oncology Regional Treatment and Diagnostic Centre
Lviv, 79031
Sumy Regional Clinical Onc Ctr
Sumy, 40005
Central Municipal Hospital - Uzhgorod State University
Uzhhorod, Chernihiv Governorate, 88017
Bosnia and Herzegovina2 sites
University Clinical Centre of the Republic of Srpska
Banja Luka, 78000
University Clinic Ctr Sarajevo
Sarajevo, 71 000
About this study
Official 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
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.
- Conditions
- Malignant Melanoma
- Being tested
- Atezolizumab, Cobimetinib
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AtezolizumabBiological
Also called Tecentriq
Atezolizumab, 840 mg intravenously every two weeks (Q2W) on Days 1 and 15 of each 28-day cycle, until loss of clinical benefit
CobimetinibDrug
Also called Cotellic
Cobimetinib, 60 mg orally once daily (QD) on Days 1-21 of each 28-day cycle, until loss of clinical benefit
AtezolizumabBiological
Also called Tecentriq
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
AtezolizumabBiological
Also called Tecentriq
Atezolizumab, 1200 mg intravenously every three weeks (Q3W) on Day 1 of each 21-day cycle, until loss of clinical benefit
| Study group | Role | What they receive |
|---|---|---|
| Cohort A | Experimental | Participants with disease progression on or after treatment with an anti-PD-1 agent will receive cobimetinib and atezolizumab treatment during 28-day cycles. Receives: Biological: Atezolizumab; Drug: Cobimetinib |
| Cohort B | Experimental | 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. Receives: Drug: Cobimetinib; Biological: Atezolizumab |
| Cohort C | Experimental | Participants with advanced melanoma, who have not received previous treatment, will receive atezolizumab monotherapy during 21-day cycles. Receives: Biological: Atezolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Investigator-Assessed 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.
Measured: Up to approximately 2 years
Investigator-Assessed 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.
Measured: Week 16
Secondary outcomes (11)
Investigator-Assessed 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.
Measured: Up to approximately 2 years
Overall Survival (OS)
OS is defined as the time from Cycle 1, Day 1 to death from any cause.
Measured: Up to approximately 2 years
Investigator-Assessed 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.
Measured: Up to approximately 2 years
Serum Concentration of Atezolizumab
Measured: Cycle 1, Day 15; Day 1 of Cycles 2, 3, 4, 8
Plasma Concentration of Cobimetinib
Measured: Cycle 1, Day 15
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.
Measured: Baseline through follow up
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.
Measured: Cycle 1 Day 1 pre-dose to 120 days after the last dose of study medication
Cohort C: Independent-Review-Committee-Assessed (IRC) 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.
Measured: Approximately 2 years for Cohorts A and B and 19 months for Cohort C
Cohort C: IRC-Assessed 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.
Measured: Approximately 21 months
Cohort C: IRC-Assessed 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.
Measured: Approximately 21 months
Cohort C: IRC-Assessed 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.
Measured: Approximately 21 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jun 2017
- Study start20 Jun 2017
- Primary completion29 May 2019
- Study completion21 Sep 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Malignant MelanomaStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 155 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03178851
- Sponsor's protocol ID
- CO39721
- Other IDs
- 2016-004402-34, 2016
- Status last verified
- Nov 2021
- First submitted
- 1 Jun 2017
- Last updated
- 19 Nov 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Sandhu S, Atkinson V, Cao MG, Medina T, Rivas AS, Menzies AM, Caro I, Roberts L, Song Y, Yan Y, Guo Y, Xue C, Long GV. Phase 1b study of cobimetinib plus atezolizumab in patients with advanced BRAFV600 wild-type melanoma progressing on prior anti-programmed death-1 therapy. Eur J Cancer. 2023 Jan;178:180-190. doi: 10.1016/j.ejca.2022.10.019. Epub 2022 Nov 2.
PubMed 36455412Barteselli G, Goodman GR, Patel Y, Caro I, Xue C, McCallum S. Characterization of Serous Retinopathy Associated with Cobimetinib: Integrated Safety Analysis of Four Studies. Drug Saf. 2022 Dec;45(12):1491-1499. doi: 10.1007/s40264-022-01248-2. Epub 2022 Oct 30.
PubMed 36310331de Azevedo SJ, de Melo AC, Roberts L, Caro I, Xue C, Wainstein A. First-line atezolizumab monotherapy in patients with advanced BRAFV600 wild-type melanoma. Pigment Cell Melanoma Res. 2021 Sep;34(5):973-977. doi: 10.1111/pcmr.12960. Epub 2021 Feb 15.
PubMed 33476492
Study at a glance
From the registry record, last updated by the sponsor on 19 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT03178851
- Acronym / sponsor ID
- CO39721
- Conditions
- Malignant Melanoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 155 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 20 Jun 2017 (actual)
- Primary completion
- 29 May 2019 (actual)
- Study completion
- 21 Sep 2020 (actual)
- First posted
- 7 Jun 2017 (actual)
- Results
- Posted 12 Jun 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cohort A | Experimental | Biological: Atezolizumab, Drug: CobimetinibParticipants with disease progression on or after treatment with an anti-PD-1 agent will receive cobimetinib and atezolizumab treatment during 28-day cycles. |
| Cohort B | Experimental | Drug: Cobimetinib, Biological: AtezolizumabParticipants 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. |
| Cohort C | Experimental | Biological: AtezolizumabParticipants with advanced melanoma, who have not received previous treatment, will receive atezolizumab monotherapy during 21-day cycles. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- 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)
- Progressed on or after anti-PD-1 therapy within 12 weeks before study start
Key exclusion criteria (41 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AtezolizumabAlso: TecentriqAtezolizumab, 840 mg intravenously every two weeks (Q2W) on Days 1 and 15 of each 28-day cycle, until loss of clinical benefit | Biological | Cohort A |
| CobimetinibAlso: CotellicCobimetinib, 60 mg orally once daily (QD) on Days 1-21 of each 28-day cycle, until loss of clinical benefit | Drug | Cohort A, Cohort B |
| AtezolizumabAlso: TecentriqAtezolizumab, 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 | Biological | Cohort B |
| AtezolizumabAlso: TecentriqAtezolizumab, 1200 mg intravenously every three weeks (Q3W) on Day 1 of each 21-day cycle, until loss of clinical benefit | Biological | Cohort C |
Primary outcome
Investigator-Assessed Objective Response Rate (ORR)
Time frame: Up to approximately 2 years
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.
Investigator-Assessed Disease Control Rate (DCR)
Time frame: Week 16
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.
11 secondary outcomes
Investigator-Assessed Duration of Response (DOR)
Time frame: Up to approximately 2 years
Overall Survival (OS)
Time frame: Up to approximately 2 years
Investigator-Assessed Progression-Free Survival (PFS)
Time frame: Up to approximately 2 years
Serum Concentration of Atezolizumab
Time frame: Cycle 1, Day 15; Day 1 of Cycles 2, 3, 4, 8
Plasma Concentration of Cobimetinib
Time frame: Cycle 1, Day 15
Percentage of Participants With Adverse Events
Time frame: Baseline through follow up
Change From Baseline in Percentage of Participants With Anti-drug Antibodies (ADAs) to Atezolizumab
Time frame: Cycle 1 Day 1 pre-dose to 120 days after the last dose of study medication
Cohort C: Independent-Review-Committee-Assessed (IRC) ORR
Time frame: Approximately 2 years for Cohorts A and B and 19 months for Cohort C
Cohort C: IRC-Assessed DCR
Time frame: Approximately 21 months
Cohort C: IRC-Assessed DOR
Time frame: Approximately 21 months
Cohort C: IRC-Assessed PFS
Time frame: Approximately 21 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Nov 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36455412Sandhu S, Atkinson V, Cao MG, Medina T, Rivas AS, Menzies AM, Caro I, Roberts L, Song Y, Yan Y, Guo Y, Xue C, Long GV. Phase 1b study of cobimetinib plus atezolizumab in patients with advanced BRAFV600 wild-type melanoma progressing on prior anti-programmed death-1 therapy. Eur J Cancer. 2023 Jan;178:180-190. doi: 10.1016/j.ejca.2022.10.019. Epub 2022 Nov 2.
- Derived from this study: PubMed 36310331Barteselli G, Goodman GR, Patel Y, Caro I, Xue C, McCallum S. Characterization of Serous Retinopathy Associated with Cobimetinib: Integrated Safety Analysis of Four Studies. Drug Saf. 2022 Dec;45(12):1491-1499. doi: 10.1007/s40264-022-01248-2. Epub 2022 Oct 30.
- Derived from this study: PubMed 33476492de Azevedo SJ, de Melo AC, Roberts L, Caro I, Xue C, Wainstein A. First-line atezolizumab monotherapy in patients with advanced BRAFV600 wild-type melanoma. Pigment Cell Melanoma Res. 2021 Sep;34(5):973-977. doi: 10.1111/pcmr.12960. Epub 2021 Feb 15.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
43 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Atezolizumab and Cobimetinib in people with Malignant Melanoma, run by Hoffmann-La Roche at 43 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 25 inclusion and 41 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 43 sites in Spain, Australia, Brazil, South Africa, United States and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Jun 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Investigator-Assessed Objective Response Rate (ORR) (time frame: Up to approximately 2 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03178851, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Nov 2021.