A phase II study of pembrolizumab and eribulin in patients with HR-positive/HER2-negative metastatic breast cancer previously treated with anthracyclines and taxanes (KELLY study)

BACKGROUND: Preliminary results with MK3475 (pembrolizumab) in heavily pretreated Estrogen Receptor (ER)-positive/ Human Epidermal Growth Factor Receptor 2 (HER2)-negative metastatic breast cancer (MBC) patients have shown promising antitumor activity. However, no data are available with anti-Programmed Death-Ligand 1 (PD-L1) agents in combination with chemotherapy in this tumor subtype in the metastatic setting. The aim of this trial is to evaluate the efficacy of pembrolizumab in combination with eribulin in patients with Hormone Receptor (HR)-positive/HER2-negative MBC who have been previously treated with an anthracycline and a taxane. TRIAL DESIGN: This is an open-label, non-randomized, multicenter phase IIA clinical trial. Patients will receive intravenously pembrolizumab (200 mg) followed by eribulin (1.23 mg/m 2 ) on day 1 of each cycle (every three weeks). Eribulin will also be administered alone on day 8 of each cycle until progression or unacceptable toxicity. The end of study will be 12 months after last study dose or progressive disease experienced in all patients. The principal selection criteria are: (1) HR-positive/HER2-negative inoperable locally recurrent or MBC; (2) prior therapy with an anthracycline and a taxane in the early or metastatic disease setting unless contraindicated; (3) at least one, but not more than two, previous chemotherapeutic regimens for locally recurrent and/or MBC; (4) measurable disease based on Response Evaluation Criteria In Solid Tumors (RECIST) v.1.1; (5) available tumor tissue for PD-L1 biomarker analysis. The primary objective of the study is to assess the efficacy of this combination as determined by the clinical benefit rate (CBR) defined as the percentage of patients who achieve complete response, partial response, or stable disease ≥24 weeks based on RECIST v.1.1. Secondary objectives evaluate: (1) safety-related outcomes and (2) efficacy measures as progression-free survival (PFS), overall survival, overall response rate (ORR), and duration of response in the intention-to-treat population and in patients with PD-L1 positive tumors. Exploratory objectives include: (1) the analysis of PFS and ORR based on irRECIST; and (2) the identification of new predictive factors of response to the combination of pembrolizumab and eribulin based on gene signatures, mutational load, and circulating tumor cells. The trial uses an exact single-stage design. We hypothesized that excluding a CBR ≤30% while targeting an improvement of the CBR to ≥50% would be an optimal approach to evaluation of the study strategy. At least 17 patients with clinical benefit among 39 evaluable patients will be adequate to justify the investigation of this strategy in further clinical trials. Considering a drop-out rate of 10%, a sample size of 44 patients will be needed to attain 80% power at nominal level of one-sided alpha of 0.05. TRIAL REGISTRATION: NCT03222856. Date of registration: July 19 th , 2017. First Patient First Visit: December 14 th , 2017. Citation Format: Jose Manuel Perez Garcia, Antonio Llombart, Jose Luis Alonso, Begona Bermejo, Lourdes Calvo, Vicente Caranana, Giuseppe Curigliano, Susana de la Cruz Sanchez, Maria Gion Cortes, Raul Marquez Vazquez, Aleix Prat, Manuel Ruiz Borrego, Miguel Sampayo, Peter Schmid, Miguel Angel Segui, Javier Cortes, Esther Holgado. A phase II study of pembrolizumab and eribulin in patients with HR-positive/HER2-negative metastatic breast cancer previously treated with anthracyclines and taxanes (KELLY study) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT152.