This phase II trial studies how well pembrolizumab and doxorubicin hydrochloride works compared to pembrolizumab with anti-estrogen therapy (anastrozole, letrozole, or exemestane) in treating patients with triple-negative or hormone-receptor positive breast cancer that has spread from the primary site (place where it started) to other places in the body. Pembrolizumab is an antibody drug that blocks a molecule called programmed death (PD)-1. PD-1 is a molecule that shuts down the body's immune responses and prevents the immune system from attacking the cancer. Doxorubicin hydrochloride is a drug used in chemotherapy that works to stop the growth of tumor cells by stopping them from dividing and by causing them to die. Anti-estrogen therapy, including anastrozole, letrozole, and exemestane, lowers estrogen levels in the body, which may help treat cancer that is hormone receptor-positive. Giving pembrolizumab together with standard treatment of either doxorubicin hydrochloride (triple-negative cancer) or anti-estrogen therapy (hormone receptor-positive cancer) may be an effective treatment for these types of breast cancer.
PRIMARY OBJECTIVES: I. To evaluate efficacy (overall response rate) of MK-3475 (pembrolizumab) and doxorubicin (doxorubicin hydrochloride) in patients with stage IV triple negative breast cancer. II. To evaluate efficacy (overall response rate) of MK-3475 and an oral aromatase inhibitor in patients with stage IV hormone receptor positive (HR+) human epidermal growth factor receptor 2 negative (HER2-) breast cancer. SECONDARY OBJECTIVES: I. To assess clinical benefit rate (lack of progression for \> 24 weeks), duration of response, time-to-treatment failure, progression-free survival, and overall survival in triple negative (TN) stage IV breast cancer patients based primarily on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and immune-related (ir)RECIST. II. To assess feasibility and toxicity. III. To assess clinical benefit rate (lack of progression for \> 24 weeks), duration of response, time-to-treatment failure, progression-free survival, and overall survival in patients with stage IV HR+ breast cancer based primarily on RECIST 1.1, and irRECIST. IV. To assess feasibility and toxicities. TERTIARY OBJECTIVES: I. To procure serial tumor (primary and metastatic) and blood (cellular and serum/plasma) samples and analyze them to better our understanding of cellular and humoral immune response correlates and predictors of clinical benefits, leading to optimized selection of target populations in future phase II and subsequent phase III randomized prospective trials. OUTLINE: Patients are assigned to 1 of 2 treatment arms. COHORT 1 (TRIPLE-NEGATIVE): Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1 and doxorubicin hydrochloride IV on day 1. Treatment repeats every 3 weeks for 6 courses, and then continues for up to 24 months with pembrolizumab alone in the absence of disease progression or unacceptable toxicity. COHORT 2 (HORMONE/HER2+): Patients receive pembrolizumab IV over 30 minutes on day 1 and an aromatase inhibitor (exemestane, anastrozole, or letrozole) orally (PO) once daily (QD) on days 1-21. Treatment repeats every 3 weeks for 24 months in the absence of disease progression or unacceptable toxicity. In both arms, patients who stop pembrolizumab with stable disease or better may receive additional pembrolizumab therapy for up to 1 year if they progress after stopping study treatment. After completion of study treatment, patients are followed up for 30 days after the end of treatment and then every 8-12 weeks thereafter.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
30
Given PO
Given IV
Given PO
Correlative studies
Given PO
Given IV
City of Hope Corona
Corona, California, United States
City of Hope Medical Center
Duarte, California, United States
City of Hope Antelope Valley
Lancaster, California, United States
City of Hope Rancho Cucamonga
Rancho Cucamonga, California, United States
City of Hope South Pasadena
South Pasadena, California, United States
City of Hope West Covina
West Covina, California, United States
Number of Participants With Overall Response
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Time frame: Up to 3 years
Clinical Benefit Rate
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial response (PR): At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR; Stable disease (SD): Neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD; Progressive disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). Clinical Benefit Rate (CBR) = CR + PR + SD at 6 months
Time frame: Up to 6 months
Overall Survival (OS)
Estimated using the product-limit method of Kaplan and Meier. From initial treatment until death from any cause.
Time frame: Up to 3 years
Progression-free Survival (PFS)
Estimated using the product-limit method of Kaplan and Meier. Failure defined as disease progression or death from any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time frame: Up to 3 years
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