Abstract OT2-01-10: Pilot study of carboplatin, nab-paclitaxel and pembrolizumab for metastatic triple-negative breast cancer (ongoing clinical trial)
Authors: Baar J , Abraham J , Silverman P , Budd GT , Vinayak S , Varadan V , Moore H , Montero A , Fu P 
Published: March 2017

Abstract
BACKGROUND. Triple-negative breast cancer (TNBC) is associated with an aggressive phenotype and decreased survival. TNBC is characterized by tumor-infiltrating lymphocytes (TIL) which predict for a better prognosis and likely reflect immune recognition of tumor-associated antigens by TIL. However, potent immune suppressive signals exist in the tumor microenvironment such as those mediated by PD-1 with its ligand, PD-L1. Therefore, to test the validity of decreasing PD-1/PD-L1-mediated immune suppression, a Phase Ib study of single-agent pembrolizumab in 32 patients with advanced TNBC showed a partial response of 16.1% and stable disease of 9.7%, thereby attesting to the effectiveness of single-agent pembrolizumab in these patients. Other studies have demonstrated that cytotoxic chemotherapy favorably modulates immunity against cancer and there is therefore a strong rationale to combine chemotherapy with an immune modulator such as pembrolizumab for the treatment of mTNBC.
TRIAL DESIGN. This is an investigator-initiated, industry-sponsored (Merck) pilot study of carboplatin (C), nab-paclitaxel (N) and pembrolizumab (P) in 30 patients with metastatic (m) TNBC. Eligible patients will receive 3 cycles of CNP, with each cycle consisting of C (AUC 6 on days 1 of a 21-day cycle), N (100 mg/m2 IV on days 1, 8 and 15 of a 21-day cycle), and P (200 mg IV on day 15 of each cycle). After completion of 3 cycles CNP, patients with responding or stable disease by RECIST 1.1 criteria will be eligible for additional cycle(s) of CNP.
ELIGIBILITY CRITERIA. Patients must have radiologically measurable mTNBC, an ECOG performance status of 0-1, must not have received more than 2 prior therapies for this disease, and must be willing to undergo a preliminary biopsy of a metastatic focus for research purposes. A second post-treatment biopsy will be encouraged but will not be mandated.
SPECIFIC AIMS. The primary objective is to determine overall response rate (ORR) in patients treated with CNP. The secondary objectives are to determine progression-free survival (PFS) and safety/tolerability of CNP. Correlative objectives include the identification of pathologic and genomic correlates of response to CNP.
STATISTICAL METHODS. Clinical response will be scored using RECIST 1.1 criteria. Under the proposed treatment, the expected clinical response is about 35%. With the precision of the 2-sided 95% confidence interval for the response rate set to 0.17 (the distance to the expected response rate of 35%), the sample size required for the study is 30 patients. The true response rate of therapy will be estimated based on the number of responses using a binomial distribution and its confidence intervals will be estimated using Wilson's method. The Kaplan-Meier method will be used to estimate PFS. Factors including pathologic and genomic correlates that predict survival outcomes will be identified by Cox model or extensions of the Cox model.
TARGET ACCRUAL. We plan to enroll 30 patients over 2 years, with the first patient expected to be enrolled in September 2016.
CONTACT INFORMATION. Joseph Baar, MD, PhD. Seidman Cancer Center of University Hospitals Case Medical Center. E-mail: joseph.baar@uhhospitals.org.
Citation Format: Baar J, Abraham J, Silverman P, Budd GT, Vinayak S, Varadan V, Moore H, Montero A, Fu P. Pilot study of carboplatin, nab-paclitaxel and pembrolizumab for metastatic triple-negative breast cancer (ongoing clinical trial) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT2-01-10.