This phase II trial studies how well atezolizumab, cobimetinib, and eribulin work in treating patients with inflammatory breast cancer that has spread to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cobimetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as eribulin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving atezolizumab, cobimetinib, and eribulin may work better in treating patients with inflammatory breast cancer.
PRIMARY OBJECTIVES: I. To determine ORR (overall response rate) of metastatic inflammatory breast cancer (BC) (mIBC) patients treated with this proposed combinatorial atezolizumab, cobimetinib, and eribulin (ACE) therapy via phase II. (ACE, Cohort I) II. To determine ORR (overall response rate) for double combination of atezolizumab and eribulin (AE). (AE, cohort II) SECONDARY OBJECTIVES: I. To further characterize the safety and tolerability of atezolizumab + cobimetinib + eribulin. II. To further characterize the safety and tolerability of atezolizumab + eribulin. III. To determine CBR (clinical benefit rate): (stable disease \[SD\] + complete response \[CR\] + partial response \[PR\] \>= 24 weeks). III. To determine the duration of response (DOR). IV. To determine progression free survival (PFS). V. To determine 2 years overall survival (OS). EXPLORATORY OBJECTIVES: I. To determine the progressive disease (PD) biomarker changes induced by combinatorial therapy using liquid and tissue based assays to investigate microenvironment via multiplex imaging, proportional study of T cells: CD3, CD8 composition and change, macrophage (M1 and M2), PD-L1 expression on circulating tumor cell (CTC). II. To determine the immune pathway related biomarker changes induced by combinatorial therapy via multiplex serum cytokine assays. III. This translational biomarker assays will be done based on collaboration with plasma based ribonucleic acid (RNA) sequencing (RNA-seq) in collaboration with Lambowitz laboratory (lab) (University of Texas at Austin \[UT Austin\]), Oncomine next-generation sequencing (NGS) study on tumor/circulating tumor deoxyribonucleic acid (ctDNA) with Wistuba lab, and bioinformatics with Futreal lab. OUTLINE: COHORT I: Patients receive atezolizumab intravenously (IV) over about 30-60 minutes every 2 weeks, cobimetinib orally (PO) daily for 3 weeks on, 1 week off for 4 weeks of the safety lead-in course. Patients then receive atezolizumab IV over about 30-60 minutes every 2 weeks, cobimetinib PO daily for 3 weeks on, 1 week off, and eribulin IV over 2-5 minutes on days 1 and 8 of cycles 1-4. Cycles 1-4 repeat every 21 days and subsequent cycles with atezolizumab and cobimetinib repeat every 28 days in the absence of disease progression or unacceptable toxicity. COHORT II: Patients receive atezolizumab IV over about 30-60 minutes every 3 weeks for cycles 1-6 and every 4 weeks for subsequent cycles, and eribulin IV over 2-5 minutes on days 1 and 8 of cycles 1-6. Cycles 1-6 repeat every 21 days and subsequent cycles with atezolizumab repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of the study treatment, patients are followed for 3 months and then every 6 months for 2 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
37
Given IV
Given PO
Given IV
Correlative studies
Correlative studies
M D Anderson Cancer Center
Houston, Texas, United States
Overall response rate (ORR)
Calculated per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. ORR is defined as the rate of patients who achieved partial response or complete response as the best response. All tumor response will be evaluated by RECIST 1.1. The ORR will be estimated along with 95% confidence intervals. Logistic regression model will be used to assess other variables' effect on the best ORR.
Time frame: Up to 2 years
Incidence of dose limiting toxicity (DLT) of cobimetinib and atezolizumab (safety lead-in)
Evaluated according to Common Terminology Criteria for Adverse Events version 4.0. DLT is defined as any treatment-emergent adverse events (AEs) occurring during the first 7 weeks (progressive disease window and cycle 1) not clearly attributable to a cause other than the study drugs.
Time frame: Up to 7 weeks
Clinical benefit rate (CBR)
Defined as the rate of patients who achieved complete response, partial response, and stable disease for \>= 24 weeks as the best response of treatment. CBR is defined as the rate of patients who achieved complete response, partial response, and stable disease for \>= 24 weeks as the best response of treatment.
Time frame: Up to 2 years
Duration of response (DOR)
Defined as the period measured from the date of the first occurrence of a complete response (CR) or partial response (PR) (whichever status is recorded first) until the first date that progressive disease or death is documented. Patients who have not progressed and who have not died by the date of data cutoff for analysis will be censored at the time of last tumor assessment date. If no tumor assessments were performed after the date of the first occurrence of a CR or PR, DOR will be censored at the date of the first occurrence of a CR or PR plus remaining stable response from that time point.
Time frame: Up to 2 years
Progression free survival (PFS)
Data from patients who have not experienced disease progression or death will be censored at the last tumor assessment date and known to be free of disease progression. Data from patients with no post-baseline tumor assessment will be censored at the treatment start date plus 1 day. PFS will be estimated using the Kaplan-Meier method and the comparison between or among patient's characteristic groups will be evaluated by log-rank test. The Cox regression model may be applied to assess the effect of covariates of interest on PFS.
Time frame: From date of treatment start until date of first documented disease progression or death, whichever occurs first, assessed up to 2 years
Overall survival (OS)
OS will be estimated using the Kaplan-Meier method and the comparison between or among patient's characteristic groups will be evaluated by log-rank test. The Cox regression model may be applied to assess the effect of covariates of interest on OS.
Time frame: At 2 years
Pharmacodynamic markers
Biomarker changes induced by combinatorial therapy using liquid and tissue based assays to investigate microenvironment via multiplex imaging, proportional study of T cells: CD3, CD8 composition and change, macrophage (M1and M2), PD-L1 expression on circulating tumor cell will be measured. Immune pathway related biomarker changes induced by combinatorial therapy via multiplex serum cytokine assays will be determined. This translational biomarker assays will be done based on collaboration with plasma based ribonucleic acid (RNA) sequencing (RNA-seq) in collaboration with Lambowitz laboratory (lab), Oncomine next-generation sequencing (NGS) study on tumor/circulating tumor deoxyribonucleic acid (ctDNA) with Wistuba lab, and bioinformatics with Futreal lab.
Time frame: Up to 2 years
Incidence of adverse events
Detailed safety and tolerability of the combination of cobimetinib, atezolizumab, and eribulin will be assessed. Toxicity data will be summarized by frequency tables.
Time frame: Up to 2 years
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