A Study of Cobimetinib Plus Paclitaxel, Cobimetinib Plus Atezolizumab Plus Paclitaxel, or Cobimetinib Plus Atezolizumab Plus Nab-Paclitaxel as Initial Treatment for Participants With Triple-Negative Breast Cancer That Has Spread

NCT02322814 | Terminated Phase 2 Results

• 2 other identifiers: WO294792014-002230-32
• Study Type: interventional
• Target: 169
• Locations: 13 countries
• Sites: 53

Brief Summary

This three-cohort, multi-stage, randomized, Phase II, multicenter trial will evaluate the safety and tolerability and estimate the efficacy of cobimetinib plus paclitaxel versus placebo plus paclitaxel in Cohort I, of cobimetinib plus atezolizumab plus paclitaxel in Cohort II, and of cobimetinib plus atezolizumab plus nab-paclitaxel in Cohort III in participants with metastatic or locally advanced, triple-negative adenocarcinoma of the breast who have not received prior systemic therapy for metastatic breast cancer (MBC). Participants may continue on study treatment until the development of progressive disease (PD) or the loss of clinical benefit, unacceptable toxicity, and/or consent withdrawal. The Cohort I target sample size is 12 participants for the safety run-in stage and approximately 90 participants in the expansion stage. Each of Cohorts II and III will consist of a safety run-in stage of approximately 15 participants followed by an expansion stage of approximately 15 participants.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (2)

• Cohort I: Progression-Free Survival, as Determined by Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

  PFS was defined as the time from randomization to the first occurrence of disease progression or relapse, as determined by the investigator, using RECIST v1.1. As per RECIST v1.1, progressive disease (PD) is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (nadir), including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm). The appearance of one or more new lesions is also considered progression.

  Randomization up to disease progression or relapse, whichever occurs first (up to approximately 2 years)

• Cohort II, III: Percentage of Participants With Confirmed Overall Response (OR) (Partial Response [PR] or Complete Response [CR]), as Determined by the Investigator Using RECIST v1.1

  OR was defined as the rate of a PR or CR occurring after randomization and confirmed \>=28 days later as determined by the investigator using RECIST v1.1. As per RECIST v1.1, CR is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to \<10 mm. PR is defined as at least a 30% decrease in the sum of diameters of all target and new measurable lesions.

  Randomization up to disease progression or relapse, whichever occurs first (up to approximately 5.25 years)

Secondary Outcomes (18)

• Cohort I, II, III: Overall Survival (OS)

  Randomization up to death from any cause (up to approximately 6.5 years)

• Cohort I: Percentage of Participants With Confirmed OR (PR or CR), as Determined by the Investigator Using RECIST v1.1

  Randomization up to disease progression or relapse, whichever occurs first (up to approximately 2 years)

• Cohort I, II, III: Duration of Response (DOR), as Determined by the Investigator Using RECIST v1.1

  Time from the first occurrence of documented objective response to time of relapse or death, whichever occurs first (up to approximately 6.5 years)

• Cohort I, II, III: Percentage of Participants With Unconfirmed Overall Response (OR_uc) (Unconfirmed PR or CR), as Determined by the Investigator Using RECIST v1.1

  Randomization up to disease progression or relapse, whichever occurs fist (up to approximately 6.5 years)

• Cohort II, III: Progression-Free Survival, as Determined by Investigator Using RECIST v1.1

  Randomization up to disease progression or relapse, whichever occurs first (up to approximately 6.5 years)

Study Arms (4)

Cohort I: Cobimetinib, Paclitaxel

EXPERIMENTAL

Participants will receive a combination of cobimetinib plus paclitaxel in 28-day cycles until disease progression, unacceptable toxicity, investigator decision, death, withdrawal of consent, or completion of study.

Drug: Cobimetinib; Drug: Paclitaxel

Cohort I: Placebo, Paclitaxel

PLACEBO COMPARATOR

Participants will receive a combination of cobimetinib placebo plus paclitaxel in 28-day cycles until disease progression, unacceptable toxicity, investigator decision, death, withdrawal of consent, or completion of study.

Drug: Paclitaxel; Drug: Placebo

Cohort II:Cobimetinib,Paclitaxel,Atezolizumab

EXPERIMENTAL

Participants will receive cobimetinib plus paclitaxel plus atezolizumab in 28-day cycles until disease progression, unacceptable toxicity, investigator decision, death, withdrawal of consent, or completion of study.

Drug: Cobimetinib; Drug: Paclitaxel; Drug: Atezolizumab

Cohort III: Cobimetinib, Nab-Paclitaxel, Atezolizumab

EXPERIMENTAL

Participants will receive cobimetinib plus nab-paclitaxel plus atezolizumab until disease progression, unacceptable toxicity, investigator decision, death, withdrawal of consent, or completion of study.

Drug: Cobimetinib; Drug: Atezolizumab; Drug: Nab-Paclitaxel

Interventions

Cobimetinib DRUG

Cobimetinib will be administered orally at a dose of 60 milligrams (mg) per day, once a day, on Day 3 through Day 23 of each 28-day treatment cycle.

Also known as: GDC-0973; RO5514041; XL518

Cohort I: Cobimetinib, Paclitaxel; Cohort II:Cobimetinib,Paclitaxel,Atezolizumab; Cohort III: Cobimetinib, Nab-Paclitaxel, Atezolizumab

Paclitaxel DRUG

Paclitaxel will be administered at a dose of 80 milligrams per square meter (mg/m\^2) by intravenous (IV) infusion on Day 1, Day 8, and Day 15 of each 28-day cycle according to prescribing information.

Cohort I: Cobimetinib, Paclitaxel; Cohort I: Placebo, Paclitaxel; Cohort II:Cobimetinib,Paclitaxel,Atezolizumab

Placebo DRUG

Placebo matching to cobimetinib will be administered orally, once a day, on Day 3 through Day 23 of each 28 day treatment cycle.

Cohort I: Placebo, Paclitaxel

Atezolizumab DRUG

Atezolizumab will be administered to Cohorts II and III at a dose of 840 mg IV every 2 weeks on Days 1 and 15 of each 28-day treatment cycle.

Also known as: MPDL3280A

Cohort II:Cobimetinib,Paclitaxel,Atezolizumab; Cohort III: Cobimetinib, Nab-Paclitaxel, Atezolizumab

Nab-Paclitaxel DRUG

Nab-Paclitaxel will be administered to Cohort III according to the local prescribing information at a starting dose of 100 mg/m\^2 by IV infusion on Days 1, 8, and 15 of each 28 day cycle.

Cohort III: Cobimetinib, Nab-Paclitaxel, Atezolizumab

Eligibility Criteria

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

You may qualify if:

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Histologically confirmed estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and human epidermal growth factor 2 (HER2)-negative adenocarcinoma of the breast with measurable metastatic or locally advanced disease
• Locally advanced disease must not be amenable to resection with curative intent
• Measurable disease, according to RECIST, v1.1
• Adequate hematologic and end organ function
• Agreement to use highly effective contraceptive methods as stated in protocol

You may not qualify if:

• Known HER2-, ER-positive, or PR-positive breast cancer by local laboratory assessment
• Any prior chemotherapy, hormonal, or targeted therapy, for inoperable locally advanced or metastatic triple-negative breast cancer (mTNBC)
• Any systemic anticancer therapy within 3 weeks prior to Cycle 1, Day 1
• Any radiation treatment to metastatic site within 28 days of Cycle 1, Day 1
• Major surgical procedure, open biopsy, or significant traumatic injury within 30 days prior to Cycle 1, Day 1 or anticipation of need for major surgical procedure during the course of the study
• Prior exposure to experimental treatment targeting rapidly accelerated fibrosarcoma (Raf), MAP kinase/ERK kinase (MEK), or the mitogen-activated protein kinase (MAPK) pathway
• Brain metastases (symptomatic or nonsymptomatic) that have not been treated previously, are progressive, or require any type of therapy (e.g., radiation, surgery, or steroids) to control symptoms from brain metastases within 30 days prior to first study treatment dose
• History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment/central serous chorioretinopathy (CSCR), retinal vein occlusion (RVO), or neovascular macular degeneration
• Cobimetinib is metabolized by the hepatic cytochrome P3A4 (CYP3A4) enzyme. Drugs CYP3A4/5 inhibitors and inducers should be avoided
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
• Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation
• History of autoimmune disease
• Prior allogenic stem cell or solid organ transplantation
• History of idiopathic pulmonary fibrosis (including pneumonitis), drug induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest computed tomography (CT) scan
• Positive test for Human Immunodeficiency Virus (HIV)

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (53)

Cancer Specialists of North Florida

Jacksonville, Florida, 32256-6932, United States

Location

Mercy Hospital, a Campus of Plantation General Hospital

Miami, Florida, 33133, United States

Location

Florida Hospital Cancer Inst

Orlando, Florida, 32804, United States

Location

Florida Cancer Research Institute

Plantation, Florida, 33324, United States

Location

Cancer Treatment Centers of America

Newnan, Georgia, 30265, United States

Location

Ingalls Memorial Hospital

Harvey, Illinois, 60426, United States

Location

Montefiore Einstein Cancer Center

The Bronx, New York, 10461, United States

Location

Magee Womens Hospital

Pittsburgh, Pennsylvania, 15213, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Avera Cancer Institute

Sioux Falls, South Dakota, 57105, United States

Location

Northwest Medical Specialties

Tacoma, Washington, 98405, United States

Location

Calvary Mater Newcastle

Waratah, New South Wales, 2298, Australia

Location

Mater Adult Hospital

South Brisbane, Queensland, 4101, Australia

Location

Peter MacCallum Cancer Centre; Medical Oncology

Melbourne, Victoria, 3000, Australia

Location

St John of God Murdoch Hospital; Oncology West

Murdoch, Western Australia, 6150, Australia

Location

Clinique Edith Cavell

Brussels, 1180, Belgium

Location

AZ Sint Lucas (Sint Lucas)

Ghent, 9000, Belgium

Location

Jessa Zkh (Campus Virga Jesse)

Hasselt, 3500, Belgium

Location

AZ Groeninge

Kortrijk, 8500, Belgium

Location

AZ Sint Augustinus Veurne

Veurne, 8630, Belgium

Location

Fakultni nemocnice Hradec Kralove

Hradec Králové, 500 05, Czechia

Location

Multiscan s.r.o.

Pardubice, 532 03, Czechia

Location

Centre Oscar Lambret

Lille, 59020, France

Location

Centre Régional de Lutte Contre Le Cancer Val D'aurelle Paul Lamarque

Montpellier, 34298, France

Location

Hopital Tenon

Paris, 75020, France

Location

Centre Eugene Marquis Centre Regional de Lutte Contre Le Cancer

Rennes, 35000, France

Location

Chaim Sheba Medical Center

Ramat Gan, 5265601, Israel

Location

Azienda Ospedaliero Universitaria Seconda Università Degli Studi Di Napoli

Napoli, Campania, 80131, Italy

Location

A.O.U Policlinico S. Orsola Malpighi di Bologna U.O di Medicina Interna Borghi - Pad.2

Bologna, Emilia-Romagna, 40138, Italy

Location

Centro Di Riferimento Oncologico; SOC Oncologia Medica C

Aviano, Friuli Venezia Giulia, 33081, Italy

Location

Policlinico Universitario Agostino Gemelli

Rome, Lazio, 00168, Italy

Location

Istituto Europeo Di Oncologia

Milan, Lombardy, 20141, Italy

Location

Azienda Ospedaliero - Universitaria Pisana U.O. Oncologia Medica 2 Universitaria ? Polo Oncologico

Pisa, Tuscany, 56126, Italy

Location

Pauls Stradins Clinical University Hospital

R?ga, LV-1002, Latvia

Location

Riga East Clinical University Hospital Latvian Oncology Centre

Riga, LV-1079, Latvia

Location

Prof. Dr. I. Chiricuta Institute of Oncology

Cluj-Napoca, 400015, Romania

Location

Oncology Center Sf. Nectarie

Craiova, 200347, Romania

Location

National Cancer Center; Medical Oncology

Gyeonggi-do, 410-769, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Korea University Guro Hospital

Seoul, 08308, South Korea

Location

Yonsei University Health System/Severance Hospital

Seoul, 120-752, South Korea

Location

Corporacio Sanitaria Parc Tauli; Servicio de Oncologia

Sabadell, Barcelona, 8208, Spain

Location

Organización Sanitaria Integrada Bilbao Basurto

Bilbao, Vizcaya, 48013, Spain

Location

Hospital Universitario Infanta Cristina; Servicio de Oncologia

Badajoz, 06080, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

Location

Fundacion Jimenez Diaz; Servicio de Oncologia

Madrid, 28040, Spain

Location

Hospital Clinico San Carlos; Servicio de Nefrologia

Madrid, 28040, Spain

Location

Hosp. Regional Univ. de Malaga ? Hospital Materno Infantil; Hospital Materno Infantil de Malaga

Málaga, 29011, Spain

Location

Chang Gung Memorial Hospital

Kaohsiung Country, 833, Taiwan

Location

Koo Foundation Sun Yat-Sen Cancer Center; Hemato-Oncology

Taipei, 11259, Taiwan

Location

Nuffield Health Bournemouth Hospital

Bournemouth, BH1 1RW, United Kingdom

Location

Mount Vernon Hospital

Middlesex, HA6 2RN, United Kingdom

Location

Nottingham University Hospitals City Campus

Nottingham, NG5 1PB, United Kingdom

Location

Related Publications (1)

• 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

MeSH Terms

Conditions

Breast Neoplasms

Interventions

cobimetinib; Paclitaxel; atezolizumab; 130-nm albumin-bound paclitaxel

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Results Point of Contact

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

genentech@druginfo.com

1-800-821-8590

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 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2014
• First Posted: December 23, 2014
• Study Start: March 12, 2015
• Primary Completion: August 10, 2018
• Study Completion: September 17, 2021
• Last Updated: April 13, 2023
• Results First Posted: November 13, 2019

Record last verified: 2023-03

Locations

RO (2); TW (2); FR (4); KR (4); ES (7); US (11); IL (1); CZ (2); AU (4); BE (5); IT (6); LA (2); GB (3)