Breast Cancer Clinical Trial
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
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.
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
Disease-Specific Exclusion Criteria
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
Cobimetinib-Specific 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 (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
Atezolizumab-Specific Exclusion Criteria (Cohorts II and III Only)
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)
Active hepatitis B (defined as having a positive hepatitis B surface antigen [HBsAg] or positive hepatitis B virus [HBV] deoxyribonucleic acid [DNA] test at screening) or hepatitis C
Active tuberculosis
Receipt of a live, attenuated vaccine within 4 weeks prior to randomization or anticipation that such a live, attenuated vaccine will be required during the study
Prior treatment with cluster of differentiation (CD) 137 (CD137) agonists or immune checkpoint blockade therapies, including anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4), anti-programmed death-1 (anti-PD-1), or anti-programmed death ligand-1 (anti-PD-L1) therapeutic antibodies
Treatment with systemic immunostimulatory agents (including but not limited to interferons or Interlukin-2 [IL-2]) within 4 weeks or five half-lives of the drug (whichever is shorter) prior to randomization
Treatment with systemic corticosteroids or other systemic immunosuppressive medications within 2 weeks prior to randomization, or anticipated requirement for systemic immunosuppressive medications during the trial
Cardiac Exclusion Criteria
History of clinically significant cardiac dysfunction
Corrected QT interval at screening greater than (>) 480 milliseconds (ms) (average of triplicate screening measurements)
Left ventricular ejection fraction (LVEF) below the institutional lower limit of normal or below 50 percent (%), whichever is lower
General Exclusion Criteria
No other history of or ongoing malignancy that would potentially interfere with the interpretation of the pharmacodynamic or efficacy assay
Pregnancy (positive serum pregnancy test) or lactation
Uncontrolled serious medical or psychiatric illness
Active infection requiring IV antibiotics on Cycle 1, Day 1
Participants who have a history of hypersensitivity reactions to paclitaxel or other drugs formulated in Cremophor® EL (polyoxyethylated castor oil) or to nab-paclitaxel and any of the excipients
Check Your Eligibility
Let’s see if you might be eligible for this study.
What is your age and gender ?
There are 51 Locations for this study
Miami Florida, 33133, United States
Orange Park Florida, 32073, United States
Orlando Florida, 32804, United States
Plantation Florida, 33324, United States
Newnan Georgia, 30265, United States
Harvey Illinois, 60426, United States
Bronx New York, 10461, United States
Pittsburgh Pennsylvania, 15213, United States
Charleston South Carolina, 29425, United States
Sioux Falls South Dakota, 57105, United States
Tacoma Washington, 98405, United States
Waratah New South Wales, 2298, Australia
South Brisbane Queensland, 4101, Australia
Melbourne Victoria, 3000, Australia
Murdoch Western Australia, 6150, Australia
Bruxelles , 1180, Belgium
Gent , 9000, Belgium
Hasselt , 3500, Belgium
Kortrijk , 8500, Belgium
Veurne , 8630, Belgium
Hradec Kralove , 500 0, Czechia
Pardubice , 532 0, Czechia
Lille , 59020, France
Montpellier , 34298, France
Paris , 75020, France
Rennes , 35000, France
Ramat Gan , 52656, Israel
Napoli Campania, 80131, Italy
Bologna Emilia-Romagna, 40138, Italy
Aviano Friuli-Venezia Giulia, 33081, Italy
Roma Lazio, 00168, Italy
Milano Lombardia, 20141, Italy
Pisa Toscana, 56126, Italy
Gyeonggi-do , 410-7, Korea, Republic of
Seoul , 05505, Korea, Republic of
Seoul , 08308, Korea, Republic of
Seoul , 120-7, Korea, Republic of
Riga , LV-10, Latvia
RÄ«ga , LV-10, Latvia
Cluj Napoca , 40001, Romania
Craiova , 20034, Romania
Sabadell Barcelona, 8208, Spain
Bilbao Vizcaya, 48013, Spain
Badajoz , 06080, Spain
Madrid , 28034, Spain
Madrid , 28040, Spain
Madrid , 28040, Spain
Malaga , 29011, Spain
Kaohsiung Country , 833, Taiwan
Taipei City , 11259, Taiwan
Bournemouth , BH1 1, United Kingdom
Middlesex , HA6 2, United Kingdom
Nottingham , NG5 1, United Kingdom
How clear is this clinincal trial information?
Please confirm you are a US based health care provider:
Yes, I am a health care Provider No, I am not a health care providerSign Up Now.
Take Control of Your Disease Journey.
Sign up now for expert patient guides, personalized treatment options, and cutting-edge insights that can help you push for the best care plan.