AzTrials
AzTrials

MelanomaPhase 3NCT02908672

A Study of Atezolizumab Plus Cobimetinib and Vemurafenib Versus Placebo Plus Cobimetinib and Vemurafenib in Previously Untreated BRAFv600 Mutation-Positive Patients With Metastatic or Unresectable Locally Advanced Melanoma

A Phase 3 study testing Atezolizumab, Cobimetinib and Vemurafenib in people with Melanoma, run by Hoffmann-La Roche at 110 sites in 20 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This is a Phase III, double-blinded, placebo-controlled, randomized, multicenter study designed to evaluate the efficacy, safety, and pharmacokinetics of atezolizumab + cobimetinib + vemurafenib compared with placebo + cobimetinib + vemurafenib in patients with previously untreated BRAFv600 mutation-positive… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Melanoma
What is being tested?
Atezolizumab, Cobimetinib and Vemurafenib
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
514 participants
Where
110 sitesin 20 countries
Study dates
13 Jan 2017to 1 Jul 2024
Phase
Phase 3
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

  • Females of child bearing potential and males with female partners must and use of contraceptive methods with a failure rate of less than or equal to (</=)1% per year is required during treatment and for 6 months post treatment. Males should not expose pregnant partners to sperm and refrain from donating sperm for 6 months post treatment. Women must refrain from donating eggs during this same period
  • Histologically confirmed Stage IV (metastatic) or unresectable Stage IIIc (locally advanced) melanoma
  • Naive to prior systemic anti-cancer therapy for melanoma (example: chemotherapy, hormonal therapy, targeted therapy, immunotherapy, or other biologic therapies) except adjuvant treatment with interferon (IFN), interleukin (IL)-2, or vaccine therapies or herbal therapies
  • Documentation of BRAFv600 mutation-positive status in melanoma tumor tissue (archival or newly obtained) through use of a clinical mutation test approved by the local health authority
  • Eastern Cooperative Oncology Group Performance (ECOG) Status of 0 or 1
  • Measurable disease according to RECIST v1.1 (must be outside central nervous system (CNS))
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  • Life expectancy >/=18 weeks
  • For participants not receiving therapeutic anticoagulation: International normalized ratio (INR) or activated partial thromboplastin time (aPTT) less than or equal to (</=) 1.5*upper limit of normal (ULN) within 28 days prior to initiation of study treatment
  • For participants receiving therapeutic anticoagulation: stable anticoagulant regimen and stable INR during the 28 days immediately preceding initiation of study treatment

Who cannot join

  • Cancer-Related Exclusion Criteria:
  • Major surgical procedure within 4 weeks prior study treatment initiation
  • Traumatic injury or palliative radiotherapy within 2 weeks prior study treatment initiation
  • Active malignancy (other than BRAFv600 mutation-positive melanoma) or malignancy within 3 years prior to screening are excluded, with the exception of resected melanoma, resected basal cell carcinoma (BCC), resected cutaneous squamous cell carcinoma (SCC), resected carcinoma in situ of the cervix, resected carcinoma in situ of the breast, in situ prostate cancer, limited-stage bladder cancer, or any other curatively treated malignancies from which the participant has been disease-free for at least 3 years
  • Ocular Exclusion Criteria:
  • History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment, central serous chorioretinopathy, retinal vein occlusion (RVO), or neovascular macular degeneration
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  • Cardiac Exclusion Criteria:
  • History of clinically significant cardiac dysfunction
  • Left ventricular ejection fraction (LVEF) below the institutional lower limit of normal or below 50%
  • Central Nervous System (CNS) Exclusion Criteria:
  • Untreated or actively progressing CNS lesions (carcinomatous meningitis)
  • History of metastases to brain stem, midbrain, pons, or medulla, or within 10 millimeter (mm) of the optic apparatus (optic nerves and chiasm); or leptomeningeal metastatic disease; or intracranial hemorrhage
  • Additional Exclusion Criteria:
  • Uncontrolled diabetes or symptomatic hyperglycemia
  • Current severe, uncontrolled systemic disease (including, but not limited to, clinically significant cardiovascular, pulmonary, or renal disease) other than cancer
  • History of malabsorption or other clinically significant metabolic dysfunction
  • Pregnant or breastfeeding, or intending to become pregnant during the study
  • Prior allogeneic stem cell or solid organ transplantation
  • History of idiopathic pulmonary fibrosis, organizing pneumonia (example: bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
  • Active or history of autoimmune disease or immune deficiency
  • Known clinically significant liver disease, inherited liver disease and active viral disease
  • Active tuberculosis
  • Treatment with therapeutic oral or intravenous (IV) antibiotics; or with a live, attenuated vaccine; or systemic immunosuppressive medication
  • Known hypersensitivity to biopharmaceutical agents produced in Chinese hamster ovary cells or any component of the atezolizumab, cobimetinib, or vemurafenib formulations
  • Any grade >/=3 hemorrhage or bleeding event within 4 weeks prior to initiation of study treatment
  • History of stroke, reversible ischemic neurological defect, or transient ischemic attack within 6 months prior to initiation of study treatment

Trial locations and contacts

110 sites in 20 countries.

110 sites in 20 countries

Germany18 sites

  • Charite - Universitätsmedizin Berlin

    Berlin, 10117

  • Elbekliniken Buxtehude

    Buxtehude, 21616

  • Klinikum d.Universität zu Köln Klinik u.Poliklinik f.Dermatologie

    Cologne, 50937

  • HELIOS Klinikum Erfurt

    Erfurt, 99089

  • Universitatsklinikum Essen

    Essen, 45147

  • Universitätsmedizin Göttingen

    Göttingen, 37075

  • Medizinische Hochschule Hannover

    Hanover, 30625

  • Universitatsklinik Heidelberg

    Heidelberg, 69120

  • UKSH Kiel

    Kiel, 24105

  • Universitätsklinikum Leipzig

    Leipzig, 04103

  • UKSH Universitatsklinikum Schleswig-Holstein

    Lübeck, 23538

  • Universitatsklinikum Mainz

    Mainz, 55131

  • Klinikum der Ludwigs-Maximilians-Universität München

    München, 80337

  • Fachklinik Hornheide

    Münster, 48157

  • Harzklinikum Dorothea Christiane Erxleben GmbH, Standort Quedlinburg

    Quedlinburg, 06484

  • Universitätsklinikum Regensburg

    Regensburg, 93053

  • Zentrum für Dermatoonkologie, Universitäts-Hautklinik Tübingen

    Tübingen, 72076

  • Universitätsklinikum Würzburg

    Würzburg, 97080

Other trials in Germany

Italy10 sites

  • Istituto Tumori ?Giovanni Paolo II?, Oncologia

    Bari, Apulia, 70124

  • Fondazione Del Piemonte Per L'oncologia Ircc Di Candiolo

    Candiolo, Piedmont, 10060

  • IRCCS Istituto Nazionale Per La Ricerca Sul Cancro (IST)

    Genoa, Liguria, 16132

  • IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola

    Meldola, Emilia-Romagna, 47014

  • Irccs Istituto Nazionale Dei Tumori (Int)

    Milan, Lombardy, 20133

  • Irccs Istituto Europeo Di Oncologia (IEO)

    Milan, Lombardy, 20141

  • IRCCS Istituto Nazionale Tumori Fondazione Pascale

    Naples, Campania, 80131

  • IFO - Istituto Regina Elena

    Rome, Lazio, 00168

  • A.O.U. Senese Policlinico Santa Maria Alle Scotte

    Siena, Tuscany, 53100

  • A.O. Universitaria S. Maria Della Misericordia Di Udine

    Udine, Friuli Venezia Giulia, 33100

Other trials in Italy

Spain9 sites

  • Hospital Universitari Vall d'Hebron

    Barcelona, 08035

  • Hospital Clínic i Provincial

    Barcelona, 08036

  • Hospital Ramon y Cajal

    Madrid, 28034

  • Hospital Universitario La Paz

    Madrid, 28046

  • Clinica Universitaria de Navarra

    Pamplona, Navarre, 31008

  • Hospital Universitario Virgen de la Macarena

    Seville, 41071

  • Fundacion Instituto Valenciano de Oncologia (IVO)

    Valencia, 04600

  • Hospital General Universitario de Valencia

    Valencia, 46014

  • Hospital Universitario Miguel Servet

    Zaragoza, 50009

Other trials in Spain

Canada8 sites

  • Arthur J.E. Child Comprehensive Cancer Center-Calgary

    Calgary, Alberta, T2N 4N2

  • Juravinski Cancer Clinic

    Hamilton, Ontario, L8V 5C2

  • LHSC - Victoria Hospital

    London, Ontario, N6A 4L6

  • Lakeridge Health Oshawa

    Oshawa, Ontario, L1G 2B9

  • The Ottawa Hospital Cancer Centre

    Ottawa, Ontario, K1H 8L6

  • CHU de Quebec - Hopital de l'Enfant-Jesus

    Québec, G1J 1Z4

  • Princess Margaret Hospital

    Toronto, Ontario, M4X 1K9

  • Cancer Care Manitoba

    Winnipeg, Manitoba, R3E 0V9

Other trials in Canada

United Kingdom8 sites

  • Bristol Haematology and Oncology centre

    Bristol, BS2 8ED

  • Beatson West of Scotland Cancer Centre

    Glasgow, G12 0YN

  • Ipswich Hospital

    Ipswich, IP4 5PD

  • St James Uni Hospital

    Leeds, LS9 7TF

  • Guys and St Thomas NHS Foundation Trust, Guys Hospital

    London, SE1 9RT

  • Freeman Hospital

    New Castle Upon Tyne, NE7 7DN

  • Singleton Hospital

    Swansea, SA2 8QA

  • Royal Cornwall Hospital

    Truro, TR1 3LJ

Other trials in United Kingdom

United States7 sites

  • St. Luke's University Health network

    Bethlehem, Pennsylvania, 18015

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35294-3300

  • Mount Sinai Medical Center

    Miami Beach, Florida, 33140

  • UC Irvine Medical Center

    Orange, California, 92868

  • UF Health Cancer Center at Orlando Health

    Orlando, Florida, 32806

  • Highlands Oncology Group

    Springdale, Arkansas, 72762

  • Arizona Oncology Associates, PC - HAL

    Tempe, Arizona, 85284

Other trials in United States

France7 sites

  • Groupe Hospitalier Saint André - Hôpital Saint André

    Bordeaux, 33075

  • Centre Hospitalier Universitaire de Grenoble - Albert Michallon

    Grenoble, 38043

  • Hopital Claude Huriez - CHU Lille

    Lille, 59037

  • CHU de Nantes

    Nantes, 44093

  • Hopital Robert Debre

    Reims, 51092

  • Centre Eugene Marquis

    Rennes, 35042

  • CHU de Rouen - Hôpital Charles Nicolle

    Rouen, 76031

Other trials in France

Poland6 sites

  • Uniwersyteckie Centrum Kliniczne

    Gdansk, 80-952

  • Narodowy Inst.Onkol.im.Sk?odowskiej-Curie Pa?stw.Inst.Badawczy Kraków

    Krakow, 31-115

  • COZL Oddzial Onkologii Klinicznej z pododdzialem Chemioterapii Dziennej

    Lublin, 20-090

  • Uniwersytecki Szpital Kliniczny w Poznaniu

    Późna, 60-355

  • Narodowy Instytut Onkologii im. Marii Sk?odowskiej-Curie - Pa?stwowy Instytut Badawczy

    Warsaw, 02-781

  • Dolno?l?skie Centrum Onkologii, Pulmonologii i Hematologii

    Wroclaw, 53-413

Other trials in Poland

Brazil5 sites

  • Centro de Pesquisa e Ensino em Oncologia de Santa Catarina - CEPEN

    Florianópolis, Santa Catarina, 88020-210

  • Hospital das Clinicas - UFRGS

    Porto Alegre, Rio Grande do Sul, 90035-003

  • Clinicas Oncologicas Integradas - COI

    Rio de Janeiro, 22290-160

  • Instituto do Cancer do Estado de Sao Paulo - ICESP

    São Paulo, São Paulo, 01246-000

  • Beneficencia Portuguesa de Sao Paulo

    São Paulo, 01321-00

Other trials in Brazil

Australia4 sites

  • Royal Adelaide Hospital

    Adelaide, South Australia, 5000

  • Peter Maccallum Cancer Centre

    Melbourne, Victoria, 3000

  • Fiona Stanley Hospital

    Murdoch, Western Australia, 6150

  • Princess Alexandra Hospital

    Woolloongabba, Queensland, 4102

Other trials in Australia

Belgium4 sites

  • Cliniques Universitaires St-Luc

    Brussels, 1200

  • UZ Leuven Gasthuisberg

    Leuven, 3000

  • CHU Sart-Tilman

    Liège, 4000

  • Sint Augustinus Wilrijk

    Wilrijk, 2610

Other trials in Belgium

Israel4 sites

  • Rambam Health Care Campus

    Haifa, 3109601

  • Sharett Institute - Hadassah Hebrew University Medical Center

    Jerusalem, 12000

  • Rabin MC

    Petah Tikva, 4941492

  • Ella Institute - Sheba Medical Center

    Ramat Gan, 5265601

Other trials in Israel

South Korea4 sites

  • Seoul National University Hospital

    Seoul, 03080

  • Severance Hospital, Yonsei University Health System

    Seoul, 03722

  • Asan Medical Center

    Seoul, 05505

  • Samsung Medical Center

    Seoul, 06351

Other trials in South Korea

Austria3 sites

  • Medical University of Graz, Department of Dermatology

    Graz, 8030

  • LKH Innsbruck

    Innsbruck, 6020

  • Medizinische Universität Wien

    Vienna, 1090

Other trials in Austria

New Zealand3 sites

  • Wellington Hospital

    Newtown, Wellington, 6021

  • Mid Central DHB

    Palmerston North, 4442

  • Tauranga Hospital, Clinical Trials Unit

    Tauranga, 3112

Other trials in New Zealand

Russia3 sites

  • Moscow City Oncology Hospital #62

    Moscovskaya Oblast, Moscow Oblast, 143423

  • FSBSI "Russian Oncological Scientific Center n.a. N.N. Blokhin"

    Moscow, Moscow Oblast, 115478

  • FBI "Scientific Research Institute of Oncology n. a. N. N. Petrov"

    Saint Petersburg, Sankt-Peterburg, DUMMY_VALUE

Other trials in Russia

Greece2 sites

  • Laiko General Hospital Athen

    Athens, 115 27

  • Metropolitan Hospital

    Pireaus, 185 47

Other trials in Greece

Hungary2 sites

  • Orszagos Onkologiai Intezet

    Budapest, 1122

  • University of Szeged Szent-Györgyi Albert Clinical Center

    Szeged, 6720

Other trials in Hungary

Portugal2 sites

  • IPO de Lisboa

    Lisbon, 1099-023

  • IPO do Porto

    Porto, 4200-072

Other trials in Portugal

Netherlands1 site

  • Erasmus Mc - Daniel Den Hoed Kliniek

    Rotterdam, 3075 EA

Other trials in Netherlands

About this study

Official title: A Phase III, Double-Blinded, Randomized, Placebo-Controlled Study of Atezolizumab Plus Cobimetinib and Vemurafenib Versus Placebo Plus Cobimetinib and Vemurafenib in Previously Untreated BRAFV600 Mutation-Positive Patients With Unresectable Locally Advanced or Metastatic Melanoma

This is a Phase III, double-blinded, placebo-controlled, randomized, multicenter study designed to evaluate the efficacy, safety, and pharmacokinetics of atezolizumab + cobimetinib + vemurafenib compared with placebo + cobimetinib + vemurafenib in patients with previously untreated BRAFv600 mutation-positive metastatic or unresectable locally advanced melanoma.

Conditions
Melanoma
Being tested
Atezolizumab, Atezolizumab Placebo, Cobimetinib, Vemurafenib, Vemurafenib Placebo
Medical subject headings
Melanoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AtezolizumabDrug

    Will be administered as per the schedule described in individual arm.

  • Atezolizumab PlaceboDrug

    Will be administered as per the schedule described in individual arm.

  • CobimetinibDrug

    Will be administered as per the schedule described in individual arm.

  • VemurafenibDrug

    Will be administered as per the schedule described in individual arm.

  • Vemurafenib PlaceboDrug

    Will be administered as per the schedule described in individual arm.

Study groups in NCT02908672
Study groupRoleWhat they receive
Atezolizumab + Cobimetinib + Vemurafenib + Vemurafenib PlaceboExperimentalRun-In Period (Cycle 1=28 days): Participants will receive vemurafenib 960 mg (four, 240 mg tablets) PO BID along with cobimetinib 60 mg (three, 20 mg tablets) PO QD on Days 1 to 21 followed by vemurafenib 720 mg (three, 240 mg tablets) PO BID on Days 22 to 28 and vemurafenib placebo (1 tablet) PO BID on Days 22 to 28. Triple Combination Period (Cycle 1 onwards): Participants will receive atezolizumab 840 mg IV infusion on Day 1 and 15, cobimetinib 60 mg (three, 20 mg tablets) PO QD on Days 1 to 21, vemurafenib 720 mg (three, 240 mg tablets) PO BID on Days 1 to 28, and vemurafenib placebo (1 tablet) PO BID on Days 1 to 28 of each 28-day cycle. Study treatment will continue until investigator-determined disease progression, death, unacceptable toxicity, withdrawal of consent, or pregnancy, whichever occurs first.
Receives: Drug: Atezolizumab; Drug: Cobimetinib; Drug: Vemurafenib; Drug: Vemurafenib Placebo
Atezolizumab Placebo + Cobimetinib + VemurafenibExperimentalRun-In Period (Cycle1=28 days): Participants will receive vemurafenib 960 milligrams (mg) (four, 240 mg tablets) orally (PO) twice a day (BID) along with cobimetinib 60 mg (three, 20 mg tablets) PO once a day (QD) on Days 1 to 21 followed by vemurafenib 960 mg (four, 240 mg tablets) PO BID on Days 22 to 28. Triple Combination Period (Cycle 1 onwards): Participants will receive ATZ placebo by intravenous (IV) infusion on Day 1 and 15, cobimetinib 60 mg (three, 20 mg tablets) PO QD on Days 1 to 21, and vemurafenib 960 mg (four, 240 mg tablets) PO BID on Days 1 to 28 of each 28-day cycle. Study treatment will continue until investigator-determined disease progression, death, unacceptable toxicity, withdrawal of consent, or pregnancy, whichever occurs first.
Receives: Drug: Atezolizumab Placebo; Drug: Cobimetinib; Drug: Vemurafenib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-Free Survival (PFS), as Determined by Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

    PFS was defined as the time from randomization to the first occurrence of PD, as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the sum of diameters (SOD) of target lesions, taking as reference smallest sum on study, including baseline. In addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of at least 5 millimeters (mm).

    Measured: Baseline up to PD or death due to any cause, whichever occurred first (up to approximately 33 months)

Secondary outcomes (13)

  1. PFS as Determined by Independent Review Committee (IRC) Using RECIST v1.1

    PFS was defined as the time from randomization to the first occurrence of disease progression, as determined by the IRC according to RECIST v1.1, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference smallest sum on study, including baseline. In addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of at least 5 mm.

    Measured: Baseline up to PD or death due to any cause, whichever occurred first (up to approximately 33 months)

  2. Percentage of Participants With Objective Response (OR), as Determined by Investigator Using RECIST V1.1

    OR rate was defined as percentage of participants with partial response (PR) or complete response (CR) on 2 consecutive occasions ≥ 4 weeks apart as determined by the investigator using RECIST v.1.1. CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD.

    Measured: Baseline up to PD or death due to any cause, whichever occurred first (up to approximately 56 months)

  3. Duration of Response (DOR), as Determined by Investigator Using RECIST v1.1

    DOR was defined as the time from the first occurrence of a documented OR to PD, as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference smallest sum on study, including baseline. In addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of at least 5 mm. CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD.

    Measured: Baseline up to PD or death due to any cause, whichever occurred first (up to approximately 56 months)

  4. Overall Survival (OS)

    OS was defined as the time from randomization to death from any cause.

    Measured: Baseline up to death due to any cause (up to approximately 85 months)

  5. Percentage of Participants Who Have Survived at 2 Years

    Percentage of participants with OS which was defined as the time from randomization to death from any cause. The Kaplan-Meier approach was used to estimate 2-year landmark survival rate. The 95% CI of landmark survival rate was calculated using the standard error derived from Greenwood's formula.

    Measured: 2 years

  6. Time to Deterioration in Global Health Status (GHS) Determined Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Scale Score

    Time to deterioration in GHS/health related quality of life (HRQoL) was defined as the time from randomization to first observed ≥ 10-point decrease in EORTC QLQ-C30 linearly transformed GHS/HRQoL scale score that is sustained for two consecutive assessments or followed by death while the participant is on treatment. EORTC QLQ-C30 consists of 30 questions that assess five aspects of participant functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, pain), GHS/QoL, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The GHS/QoL are scored on a 7-point scale (1=Very Poor to 7=Excellent). The obtained scores are linearly transformed to a score range of 0-100, where higher scores indicate a higher response level and better QoL.

    Measured: Baseline up to PD or death due to any cause, whichever occurred first (up to approximately 33 months)

  7. Time to Deterioration in Physical Functioning (PF) Determined Using EORTC QLQ-C30 Scale Score

    Time to deterioration in PF = time from randomization to first observed ≥ 10-point decrease in EORTC QLQ-C30 linearly transformed PF scale score that is sustained for two consecutive assessments or followed by death while the participant is on treatment. EORTC QLQ-C30 consists of 30 questions that assess 5 aspects of participant functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, pain), GHS/QoL, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). PF scale has 5 questions about participant's PF and daily activities (strenuous activities, long walks, short walks, bed/chair rest \& needing help with eating, dressing, washing themselves, or using the toilet). PF are scored on a 4-point scale (1=Not at All to 4=Very Much). The obtained scores are linearly transformed to a score range of 0-100, where higher scores indicate a higher response level, functioning/support.

    Measured: Baseline up to PD or death due to any cause, whichever occurred first (up to approximately 33 months)

  8. Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

    An AE is any untoward medical occurrence in a participant when administered a pharmaceutical product regardless of the causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom/disease temporally associated with the use of an investigational product, whether or not considered related to the investigational product. A SAE is any significant hazard, contraindication, side effect that is fatal or life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is medically significant or requires intervention to prevent one or other of the outcomes listed above. All AEs were reported until 30 days and SAEs until 90 days after the final dose of study treatment or until initiation of subsequent anti-cancer therapy, whichever occurred first.

    Measured: Up to approximately 85 months

  9. Serum Concentration of Atezolizumab

    Measured: Pre-infusion Day 1 of Cycles 1-4; 30 minutes post-infusion Day 1 of Cycles 1 and 4; at Atezolizumab discontinuation (up to approximately 33 months) (1 Cycle = 28 days)

  10. Plasma Concentration of Cobimetinib Dose: 20/40 mg

    Measured: Pre-dose (0 hour) and 3 to 6 hours post dose on Day 15 of Cycles 1 and 4 (1 Cycle = 28 days)

  11. Plasma Concentration of Cobimetinib Dose: 60 mg

    Measured: Pre-dose (0 hour) and 3 to 6 hours post dose on Day 15 of Cycles 1 and 4 (1 Cycle = 28 days)

  12. Plasma Concentration of Vemurafenib

    Measured: Pre-dose (0 hour) and 3 to 6 hours post dose on Day 15 of Cycles 1 and 4 (1 Cycle = 28 days)

  13. Percentage of Participants Positive for Anti-drug Antibodies (ADA) to Atezolizumab

    Presence of ADAs against atezolizumab during the study relative to the presence of ADAs at baseline. The percentage of ADA-positive participants after drug administration were determined for participants exposed to atezolizumab. For determining post-baseline incidence, participants were considered to be ADA-positive if they were ADA-negative or had missing data at baseline but developed an ADA response following study drug exposure, or if they were ADA-positive at baseline and the titer of 1 or more post-baseline samples was at least 0.60 titer units (t.u.) greater than the baseline titer result.

    Measured: Pre-infusion Day 1 of Cycles 1-4 (1 Cycle=28 days); at Atezolizumab discontinuation (approximately up to 33 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Sep 2016 (estimated)
  2. Study start13 Jan 2017
  3. Primary completion11 Oct 2019
  4. Study completion1 Jul 2024

Resources

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
514 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02908672
Sponsor's protocol ID
CO39262
Other IDs
2016-002482-54, 2016
Status last verified
Jun 2025
First submitted
19 Sep 2016
Last updated
20 Jul 2025

Publications

  • Li SN, Wan X, Peng LB, Li YM, Li JH. Cost-effectiveness of immune checkpoint inhibition and targeted treatment in combination as adjuvant treatment of patient with BRAF-mutant advanced melanoma. BMC Health Serv Res. 2023 Jan 18;23(1):49. doi: 10.1186/s12913-023-09058-7.

    PubMed 36653848

  • Ascierto PA, Stroyakovskiy D, Gogas H, Robert C, Lewis K, Protsenko S, Pereira RP, Eigentler T, Rutkowski P, Demidov L, Zhukova N, Schachter J, Yan Y, Caro I, Hertig C, Xue C, Kusters L, McArthur GA, Gutzmer R. Overall survival with first-line atezolizumab in combination with vemurafenib and cobimetinib in BRAFV600 mutation-positive advanced melanoma (IMspire150): second interim analysis of a multicentre, randomised, phase 3 study. Lancet Oncol. 2023 Jan;24(1):33-44. doi: 10.1016/S1470-2045(22)00687-8. Epub 2022 Nov 29.

    PubMed 36460017

  • Robert C, Lewis KD, Gutzmer R, Stroyakovskiy D, Gogas H, Protsenko S, Pereira RP, Eigentler T, Rutkowski P, Demidov L, Caro I, Forbes H, Shah K, Yan Y, Li H, McArthur GA, Ascierto PA. Biomarkers of treatment benefit with atezolizumab plus vemurafenib plus cobimetinib in BRAFV600 mutation-positive melanoma. Ann Oncol. 2022 May;33(5):544-555. doi: 10.1016/j.annonc.2022.01.076. Epub 2022 Feb 4.

    PubMed 35131452

  • de 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

  • Gutzmer R, Stroyakovskiy D, Gogas H, Robert C, Lewis K, Protsenko S, Pereira RP, Eigentler T, Rutkowski P, Demidov L, Manikhas GM, Yan Y, Huang KC, Uyei A, McNally V, McArthur GA, Ascierto PA. Atezolizumab, vemurafenib, and cobimetinib as first-line treatment for unresectable advanced BRAFV600 mutation-positive melanoma (IMspire150): primary analysis of the randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2020 Jun 13;395(10240):1835-1844. doi: 10.1016/S0140-6736(20)30934-X.

    PubMed 32534646

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Atezolizumab, Cobimetinib and Vemurafenib in people with Melanoma, run by Hoffmann-La Roche at 110 sites in 20 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 9 inclusion and 26 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 20 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 110 sites in Germany, Italy, Spain, Canada, United Kingdom and 15 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 19 Nov 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?

Progression-Free Survival (PFS), as Determined by Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (time frame: Baseline up to PD or death due to any cause, whichever occurred first (up to approximately 33 months)). 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 NCT02908672, which also lists 5 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 20 Jul 2025.

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