Abstract OT1-02-05: A single arm phase II study of adjuvant anti-PD1 (pembrolizumab) in combination with hormonal therapy in patients with hormone receptor (HR)-positive localized inflammatory breast cancer (IBC) who did not achieve a pathological complete response (pCR) to neoadjuvant chemotherapy
Authors: Alexander A , Willey J , Sun H , Parker CA , Marx AN , Wood AL , Reddy SM , Reuben JM , Bassett RL , Le-Petross HT , Krishnamurthy S , Gong Y , Woodward WA , Valero V , Ueno NT , Lim B 
Published: February 2018

Abstract
Background: The pCR rate to conventional chemotherapy in hormone receptor positive IBC has historically been low (7.4% for HR+ HER2-, and 30% for HR+ HER2+), and despite the use of adjuvant endocrine therapy, the recurrence rate is still as high as 40%. To date, no targeted agent is proven to improve the efficacy of adjuvant endocrine therapy within the IBC population to improve this poor disease free survival (DFS). One plausible reason for the poor efficacy of endocrine therapy is a suppressed immune system, which allows tumor cells to avoid detection despite expression of potential immunogenic surface antigens.
Trial Design: This is a single arm trial that will enroll stage III HR+ IBC patients who have completed neoadjuvant therapy but had residual disease at mastectomy. Enrollment should be before or within 2 months of beginning endocrine therapy. Monitoring of DFS will be done with radiological imaging every 3 cycles (starting at cycle 4) as clinically indicated, per standard of care. Pembrolizumab is given on day 1 of each 21 day cycle for up to 2 years if the disease is controlled, and hormonal therapy will be administered per standard of care.
Eligibility Criteria: Clinical stage 3 IBC ER+/PR+ and HER2 negative patients who completed neoadjuvant chemotherapy and surgery with evidence of residual cancer in the breast or lymph nodes, but be clinically disease-free with good performance status at the start of study. Patients also must have adequate hematologic and organ function, and have recovered from the acute effects from prior treatments.
Specific Aims: The primary objective is to determine the disease free survival (DFS) at 2 years of patients with adjuvant therapy using Pembrolizumab in combination with standard adjuvant hormonal therapy. The secondary objective is to determine the safety and toxicity profile of this combination.
Statistical Methods: With a sample size of 37 patients, assuming that 80% are alive (20% increase from historical data) and disease-free at 2 years, and all patients are followed for &gt;2 years after enrollment with no dropout, a 95% confidence interval around the 2-year estimate of DFS will be generated. DFS will then be compared with the historical control rate of 60% by year 2 using a one-sided exponential MLE test.
Accrual: To date we have enrolled 3 patients since activation in January 2017, and the target enrollment is 37 patients.
Contact information: For more information or to refer a patient, please contact study coordinator, Angela Alexander - aalexand@mdanderson.org
Citation Format: Alexander A, Willey J, Sun H, Parker CA, Marx AN, Wood AL, Reddy SM, Reuben JM, Bassett RL, Le-Petross HT, Krishnamurthy S, Gong Y, Woodward WA, Valero V, Ueno NT, Lim B. A single arm phase II study of adjuvant anti-PD1 (pembrolizumab) in combination with hormonal therapy in patients with hormone receptor (HR)-positive localized inflammatory breast cancer (IBC) who did not achieve a pathological complete response (pCR) to neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT1-02-05.