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

Stopped early · Phase 2 · Has a placebo group

Conditions studied: Breast Cancer

In brief

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.

Key facts

Study ID

NCT02322814

Run by

Hoffmann-La Roche

People needed

169

Starts

2015-03-12

Expected to finish

2021-09-17

Last updated by the study team

2023-04-13

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

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…

• 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

Where it is running

• Mercy Hospital, a Campus of Plantation General Hospital — Miami, Florida, United States
• Florida Hospital Cancer Inst — Orlando, Florida, United States
• Florida Cancer Research Institute — Plantation, Florida, United States
• Cancer Treatment Centers of America — Newnan, Georgia, United States
• Ingalls Memorial Hospital — Harvey, Illinois, United States
• Montefiore Einstein Cancer Center — The Bronx, New York, United States
• Magee Womens Hospital — Pittsburgh, Pennsylvania, United States
• Medical University of South Carolina — Charleston, South Carolina, United States
• Avera Cancer Institute — Sioux Falls, South Dakota, United States
• Northwest Medical Specialties — Tacoma, Washington, United States
• Calvary Mater Newcastle — Waratah, New South Wales, Australia
• Mater Adult Hospital — South Brisbane, Queensland, Australia
• Peter MacCallum Cancer Centre; Medical Oncology — Melbourne, Victoria, Australia
• St John of God Murdoch Hospital; Oncology West — Murdoch, Western Australia, Australia
• Clinique Edith Cavell — Brussels, Belgium
• AZ Sint Lucas (Sint Lucas) — Ghent, Belgium
• Jessa Zkh (Campus Virga Jesse) — Hasselt, Belgium
• AZ Groeninge — Kortrijk, Belgium
• AZ Sint Augustinus Veurne — Veurne, Belgium
• Fakultni nemocnice Hradec Kralove — Hradec Králové, Czechia
• Multiscan s.r.o. — Pardubice, Czechia
• Centre Oscar Lambret — Lille, France
• Centre Régional de Lutte Contre Le Cancer Val D'aurelle Paul Lamarque — Montpellier, France
• Hopital Tenon — Paris, France
• Cancer Specialists of North Florida — Jacksonville, Florida, United States

Full record on ClinicalTrials.gov

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