Last updated on January 2019

Pembrolizumab Letrozole and Palbociclib in Treating Postmenopausal Patients With Newly Diagnosed Metastatic Stage IV Estrogen Receptor Positive Breast Cancer

Brief description of study

This phase II trial studies how well pembrolizumab works when given together with letrozole and palbociclib in treating postmenopausal patients with newly diagnosed stage IV estrogen receptor positive breast cancer that has spread to other parts of the body. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread. Estrogen can cause the growth of breast cancer cells. Antihormone therapy, such as letrozole, may lessen the amount of estrogen made by the body. Palbociclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving pembrolizumab, letrozole, and palbociclib may be an effective treatment for patients with stage IV estrogen receptor positive breast cancer.

Detailed Study Description


I. To evaluate the objective response rate (ORR), based on Response Evaluation Criteria in Solid Tumors [RECIST], version 1.1), of pembrolizumab in combination with letrozole and palbociclib in patients with newly diagnosed metastatic estrogen receptor (ER)+human epidermal growth factor receptor (HER)2- breast cancer, and determine if the addition of pembrolizumab to letrozole and palbociclib combination can achieve an improved response rate (ORR = complete response [CR] + partial response [PR]) measured from the study baseline, based on RECIST version 1.1.


I. To determine the safety and tolerability of adding pembrolizumab (200 mg every 3 weeks) to letrozole (2.5 mg) and palbociclib (125 mg 3 weeks on, one week off) in patients with metastatic ER+HER2- breast cancer.

II. To evaluate the CR rate.

III. To evaluate progression-free survival (PFS).

IV. To evaluate overall survival (OS).

V. To evaluate duration of response (DOR) using RECIST version 1.1.

VI. To evaluate clinical benefit rate (CBR) using RECIST version 1.1.

VII. To evaluate toxicities (using the National Cancer Institute [NCI] Common Terminology Criteria for adverse Events [CTCAE], version 4.0) associated with the triple drug combination (pembrolizumab, letrozole, and palbociclib) in patients with metastatic ER+HER2- breast cancer.

VIII. To evaluate CR, PR, ORR, PFS, DOR, and CBR using immune-related Response Criteria In Solid Tumors (irRECIST); time to treatment failure will also be assessed.


I. To study cellular/humoral immune response by analyzing immune and stromal cell characteristics before and after treatment that correlate with clinical response; this includes programmed cell death 1 ligand 1 (PD-L1) expression levels.

II. To study the peripheral serum thymidine kinase (TK) level and its association with treatment response.

III. To study circulating tumor deoxyribonucleic acid (DNA) (ctDNA) and the effect of combining pembrolizumab, letrozole, and palbociclib on ctDNA profiles.

IV. To evaluate genomic and phenotypic status of breast tumor.


Patients receive letrozole orally (PO) once daily (QD) on days 1-28 and palbociclib PO QD for 3 weeks. Courses with letrozole and palbociclib repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Courses with pembrolizumab repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, every 6 months for 3 years, and then every 12 months for 1 year.

Clinical Study Identifier: NCT02778685

Contact Investigators or Research Sites near you

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Valerie Estala

City of Hope Rancho Cucamonga
Rancho Cucamonga, CA United States
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Recruitment Status: Open

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