A Study to Investigate Efficacy and Safety of Cobimetinib Plus Atezolizumab and Atezolizumab Monotherapy Versus Regorafenib in Participants With Metastatic Colorectal Adenocarcinoma (COTEZO IMblaze370)

NCT02788279 | Completed Phase 3 Results

• 2 other identifiers: GO301822016-000202-11
• Study Type: interventional
• Target: 363
• Locations: 11 countries
• Sites: 73

Brief Summary

This is a Phase III, multicenter, open-label, three-arm, randomized study in participants with unresectable locally advanced or metastatic colorectal cancer (CRC) who have received at least two prior regimens of cytotoxic chemotherapy for metastatic disease. The study compares regorafenib, a standard of care therapy in this setting, to cobimetinib plus atezolizumab and atezolizumab monotherapy.

Conditions

Colorectal Cancer

Keywords

Locally advanced or Metastatic colorectal adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS)

  Overall survival is defined as the time (in months) between the date of randomization and the date of death due to any cause. Participants who were not reported as having died at the date of analysis were censored at the date when they were last known to be alive. Participants who did not have post-baseline information were censored at the date of randomization + 1 day. Median OS was estimated by Kaplan-Meier method and 95% CI was assessed using the method of Brookmeyer and Crowley.

  From randomization up to death due to any cause (up to approximately 20 months)

Secondary Outcomes (9)

• Progression-Free Survival (PFS) as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

  From randomization up to disease progression or death due to any cause (up to approximately 20 months)

• Percentage of Participants With Investigator-Assessed Objective Response of Complete Response (CR) or Partial Response (PR) According to RECIST Version 1.1

  From randomization up to death due to any cause (up to approximately 20 months)

• Duration of Response (DOR) According to RECIST Version 1.1

  From first occurrence of CR or PR up to disease progression or death due to any cause (up to approximately 20 months)

• Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Physical Functioning Sub-scale Score

  Baseline, end of the study (up to approximately 2.5 years)

• Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life-C30 Questionnaire (EORTC QLQ-C30) Global Quality of Life Sub-scale Score at the End of the Study

  Baseline, end of the study (up to approximately 2.5 years)

Study Arms (3)

Atezolizumab

EXPERIMENTAL

Participants will receive atezolizumab monotherapy 1200 milligrams (mg) intravenous (IV) on Day 1 in a 21-day cycle until disease progression according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, unacceptable toxicity, death, participant's or physician decision to withdraw, or pregnancy, whichever occurs first.

Drug: Atezolizumab (MPDL3280A), an Engineered Anti-PDL1 Antibody

Cobimetinib + Atezolizumab

EXPERIMENTAL

Participants will receive cobimetinib 60 mg orally on Days 1 to 21 plus atezolizumab 840 mg IV on Day 1 and Day 15 in a 28-day cycle until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant's or physician decision to withdraw, or pregnancy, whichever occurs first.

Drug: Atezolizumab (MPDL3280A), an Engineered Anti-PDL1 Antibody; Drug: Cobimetinib

Regorafenib

ACTIVE COMPARATOR

Participants will receive regorafenib 160 mg orally on Days 1 to 21 in a 28-day cycle until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant's or physician decision to withdraw, or pregnancy, whichever occurs first.

Drug: Regorafenib

Interventions

Atezolizumab (MPDL3280A), an Engineered Anti-PDL1 Antibody DRUG

Participants will receive atezolizumab IV at 840 mg on Day 1 and Day 15 in a 28-day cycle as a combination therapy or at 1200 mg on Day 1 in a 21-day cycle as a monotherapy until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant's or physician decision to withdraw, or pregnancy, whichever occurs first.

Atezolizumab; Cobimetinib + Atezolizumab

Cobimetinib DRUG

Participants will receive cobimetinib 60 mg orally on Days 1 to 21 in a 28-day cycle as a combination therapy until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant's or physician decision to withdraw, or pregnancy, whichever occurs first.

Cobimetinib + Atezolizumab

Regorafenib DRUG

Participants will receive regorafenib 160 mg orally on Days 1 to 21 in a 28-day cycle until disease progression according to RECIST Version 1.1, unacceptable toxicity, death, participant's or physician decision to withdraw, or pregnancy, whichever occurs first.

Regorafenib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed adenocarcinoma originating from the colon or rectum (Stage 4 American Joint Committee on Cancer \[AJCC\] 7th edition)
• Experienced disease progression or was intolerant to at least two systemic chemotherapy regimens for metastatic colorectal cancer that must have included fluroropyrimidines, irinotecan, and oxaliplatin; adjuvant regimen can be considered as one chemotherapy regimen for metastatic disease if the participant had disease recurrence within 6 months of completion; disease progression must have occurred within 3 months of the last systemic therapy administration
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Anticipated life expectancy greater than or equal to (\>=) 3 months
• Adequate hematologic and end organ function
• Women of childbearing potential must agree to appropriately use an effective form of contraception (failure rate of less than \[\<\] 1 percent \[%\] per year) during the treatment period, within 5 months after the last dose of atezolizumab, and within 3 months after the last dose of cobimetinib and regorafenib
• Men must agree not to donate sperm or have intercourse with a female partner without using appropriate barrier contraception during the treatment period and for 3 months after the last dose of either cobimetinib or regorafenib
• Provide an archival or newly obtained tumor tissue sample

You may not qualify if:

• After the approximate 5% cap for microsatellite (MSI)-high participants is reached, only MSI-stable participants will be eligible
• Once the 50% cap for wild-type RAS has been reached, only extended RAS-mutant participants will be eligible
• Major surgery or radiotherapy within 21 days prior to Cycle 1 Day 1 or anticipation of needing such procedure while receiving study treatment
• Treatment with any anti-cancer agent within 14 days prior to Cycle 1 Day 1
• Uncontrolled tumor-related pain. Participants requiring narcotic pain medication must be on a stable regimen at study entry
• Uncontrolled pleural effusion, pericardial effusion or ascites requiring repeated drainage more than once every 28 days. Indwelling drainage catheters (e.g., PleurX®) are allowed
• Active or untreated central nervous system (CNS) metastases are excluded
• Prior therapy with any cancer immunotherapy, MEK inhibitor, or regorafenib
• Participants with active malignancy (other than CRC) or a prior malignancy within the past 3 years are excluded. Participants with completely resected cutaneous melanoma (early stage), basal cell carcinoma, cutaneous squamous cell carcinoma, cervical carcinoma in-situ, breast carcinoma in-situ, and localized prostate cancer are eligible
• Unstable angina, new onset angina within last 3 months, myocardial infarction within last 6 months and current congestive heart failure New York Heart Association Class II or higher
• Left ventricular ejection fraction (LVEF) below institutional lower limit of normal or below 50%, whichever is lower
• Poorly controlled hypertension, defined as a blood pressure consistently above 150/90 millimeters of Mercury (mmHg) despite optimal medical management
• Human immunodeficiency virus (HIV) infection
• Active tuberculosis infection
• Severe infections within 2 weeks prior to Cycle 1 Day 1

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (73)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

Yale Cancer Center; Medical Oncology

New Haven, Connecticut, 06520, United States

Location

Georgetown University

Washington D.C., District of Columbia, 20007, United States

Location

Florida Cancer Specialists; SCRI

Fort Myers, Florida, 33901, United States

Location

Cancer Specialists; North Florida ;Jacksonville (AC Skinner Pkwy)

Jacksonville, Florida, 32256, United States

Location

Florida Cancer Specialists.

St. Petersburg, Florida, 33705, United States

Location

Ingalls Cancer Research Center

Harvey, Illinois, 60426, United States

Location

Southdale Cancer Clinic U of M Medical Center, Fairview- Edina

Edina, Minnesota, 55435, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

North Shore Hem Onc Associates

East Setauket, New York, 11733, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

INTEGRIS Cancer Inst of OK

Oklahoma City, Oklahoma, 73142, United States

Location

University of Pittsburgh Cancer Institute; Division of Medical Oncology

Pittsburgh, Pennsylvania, 15232, United States

Location

SCRI Tennessee Oncology Chattanooga

Chattanooga, Tennessee, 37404, United States

Location

Sarah Cannon Research Inst.

Nashville, Tennessee, 37203, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Medical Oncology Associates

Spokane, Washington, 99208, United States

Location

Port Macquarie Base Hospital;North Coast Cancer Institute

Port Macquarie, New South Wales, 2444, Australia

Location

Northern Cancer Institute

St Leonards, New South Wales, 2065, Australia

Location

Sydney Adventist Hospital; Clinical Trial Unit

Sydney, New South Wales, 2076, Australia

Location

Monash Medical Centre; Oncology

Clayton, Victoria, 3168, Australia

Location

Peninsula and South Eastern Haematology and Oncology Group

Frankston, Victoria, 3199, Australia

Location

Austin Health; Cancer Clinical Trial Centre

Heidelberg, Victoria, 3084, Australia

Location

Imeldaziekenhuis

Bonheiden, 2820, Belgium

Location

Cliniques Universitaires St-Luc

Brussels, 1200, Belgium

Location

GHdC Site Notre Dame

Charleroi, 6000, Belgium

Location

AZ Groeninge

Kortrijk, 8500, Belgium

Location

UZ Leuven Gasthuisberg

Leuven, 3000, Belgium

Location

Tom Baker Cancer Centre-Calgary

Calgary, Alberta, T2N 4N2, Canada

Location

Cross Cancer Institute; Clinical Trials

Edmonton, Alberta, T6G 1Z2, Canada

Location

BCCA-Vancouver Cancer Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

The Ottawa Hospital

Ottawa, Ontario, K1H 8L6, Canada

Location

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

Location

McGill University Health Center, Cedar Cancer Center

Montreal, Quebec, H3G 1A4, Canada

Location

Hopital du Sacre-Coeur

Montreal, Quebec, J4B 5Z7, Canada

Location

CHU de Québec

Québec, Quebec, G1J 1Z4, Canada

Location

Queen Mary Hospital; Dept. of Clinical Oncology

Hong Kong, Hong Kong

Location

Tuen Mun Hospital; Clinical Oncology

Hong Kong, Hong Kong

Location

Prince of Wales Hosp; Dept. Of Clinical Onc

Shatin, Hong Kong

Location

IRCCS Ospedale Casa Sollievo Della Sofferenza; Oncologia

San Giovanni Rotondo, Apulia, 71013, Italy

Location

Azienda Osp Uni Seconda Università Degli Studi Di Napoli; Unità Operativa Oncologia Medica

Napoli, Campania, 80131, Italy

Location

A.O. Universitaria Policlinico Di Modena; Oncologia

Modena, Emilia-Romagna, 41100, Italy

Location

Istit. Naz. per la Ricerca sul Cancro - Az. Osped. S. Martino

Genoa, Liguria, 16132, Italy

Location

Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 1

Milan, Lombardy, 20133, Italy

Location

Asst Grande Ospedale Metropolitano Niguarda; Dipartimento Di Ematologia Ed Oncologia

Milan, Lombardy, 20162, Italy

Location

A.O. Universitaria Pisana; Oncologia

Pisa, Tuscany, 56100, Italy

Location

Centrum Onkologii im. Prof. F. Lukaszczyka w Bydgoszczy

Bydgoszcz, 85-796, Poland

Location

Uniwersyteckie Centrum Kliniczne; Klinika Onkologii i Radioterapii

Gdansk, 80-214, Poland

Location

Szpitale Pomorskie Sp. z o. o.

Gdynia, 81-519, Poland

Location

Szpital Uniwersytecki w Krakowie, Oddział Kliniczny Kliniki Onkologii

Krakow, 31-531, Poland

Location

Woj.Wielospecjalistyczne Centrum Onkologii i Traumatologii; Oddz.Hematologii Pododz.Chemioterapii

Lodz, 93-513, Poland

Location

Arkhangelsk Regional Clinical Oncology Dispensary

Arkhangelsk, 163045, Russia

Location

N.N.Burdenko Main Military Clinical Hospital; Oncology Dept

Moscow, 105229, Russia

Location

BHI of Omsk region Clinical Oncology Dispensary

Omsk, 644013, Russia

Location

National Cancer Center

Gyeonggi-do, 10408, South Korea

Location

Chonnam National University Hwasun Hospital

Jeollanam-do, 58128, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Asan Medical Center - Oncology

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Yonsei University Health System/Severance Hospital

Seoul, 120-752, South Korea

Location

Hospital de Navarra; Servicio de Oncologia

Navarra, Navarre, 31008, Spain

Location

Hospital Univ Vall d'Hebron; Servicio de Oncologia

Barcelona, 08035, Spain

Location

Hospital Ramon y Cajal; Servicio de Oncologia

Madrid, 28034, Spain

Location

Hospital Clinico San Carlos; Servicio de Oncologia

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre; Servicio de Oncologia

Madrid, 28041, Spain

Location

Hospital Clínico Universitario de Valencia; Servicio de Oncología

Valencia, 46010, Spain

Location

Birmingham Heartlands Hospital; Dept of Oncology

Birmingham, B9 5SS, United Kingdom

Location

Royal Marsden Hospital - Fulham; Oncology Department

London, SW3 6JJ, United Kingdom

Location

The Christie; GI Research Office

Manchester, M20 4BX, United Kingdom

Location

Churchill Hospital; Department of Oncology

Oxford, OX3 7LE, United Kingdom

Location

Queen's Hospital

Romford, RM7 0AG, United Kingdom

Location

Weston Park Hospital; Cancer Clinical Trials Centre

Sheffield, S10 2SJ, United Kingdom

Location

Royal Marsden Hospital; Dept of Medical Oncology

Sutton, SM2 5PT, United Kingdom

Location

Related Publications (3)

• Taraborrelli L, Senbabaoglu Y, Wang L, Lim J, Blake K, Kljavin N, Gierke S, Scherl A, Ziai J, McNamara E, Owyong M, Rao S, Calviello AK, Oreper D, Jhunjhunwala S, Argiles G, Bendell J, Kim TW, Ciardiello F, Wongchenko MJ, de Sauvage FJ, de Sousa E Melo F, Yan Y, West NR, Murthy A. Tumor-intrinsic expression of the autophagy gene Atg16l1 suppresses anti-tumor immunity in colorectal cancer. Nat Commun. 2023 Sep 23;14(1):5945. doi: 10.1038/s41467-023-41618-7.

  PMID: 37741832 DERIVED

• Barteselli 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.

  PMID: 36310331 DERIVED

• Eng C, Kim TW, Bendell J, Argiles G, Tebbutt NC, Di Bartolomeo M, Falcone A, Fakih M, Kozloff M, Segal NH, Sobrero A, Yan Y, Chang I, Uyei A, Roberts L, Ciardiello F; IMblaze370 Investigators. Atezolizumab with or without cobimetinib versus regorafenib in previously treated metastatic colorectal cancer (IMblaze370): a multicentre, open-label, phase 3, randomised, controlled trial. Lancet Oncol. 2019 Jun;20(6):849-861. doi: 10.1016/S1470-2045(19)30027-0. Epub 2019 Apr 16.

  PMID: 31003911 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

atezolizumab; cobimetinib; regorafenib

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 27, 2016
• First Posted: June 2, 2016
• Study Start: July 5, 2016
• Primary Completion: March 9, 2018
• Study Completion: December 26, 2018
• Last Updated: December 11, 2019
• Results First Posted: June 18, 2019

Record last verified: 2019-11

Locations

GB (7); ES (6); IT (7); KR (6); US (17); PL (5); BE (5); HK (3); CA (8); RU (3); AU (6)