Abstract P5-15-02: Phase 1b/2 study to evaluate eribulin mesylate in combination with pembrolizumab in patients with metastatic triple-negative breast cancer
Authors: Tolaney S , Savulsky C , Aktan G , Xing D , Almonte A , Karantza V , Diab S 
Published: March 2017

Abstract
Background: Eribulin, a non-taxane microtubule inhibitor, is approved for the treatment of (1) patients (pts) with advanced or metastatic breast cancer (MBC) who have received ≥1 [European Union] or ≥2 [United States] prior chemotherapy regimens for metastatic disease, including an anthracycline and taxane in either the adjuvant or metastatic setting and (2) pts with unresectable or metastatic liposarcoma who have received a prior anthracycline regimen. Pembrolizumab is a human programmed death receptor-1 (PD-1)-blocking antibody approved for the treatment of (1) pts with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAFV600-mutation positive, a BRAF inhibitor and (2) pts with advanced non-small cell lung cancer with tumors expressing PD-L1. Pembrolizumab is also being evaluated for the treatment of metastatic triple-negative breast cancer (mTNBC) and other tumor types. Here, we report an interim analysis from an open-label, single-arm, multicenter, phase 1b/2 study to evaluate the safety and efficacy of the eribulin and pembrolizumab combination in pts with mTNBC previously treated in the metastatic setting.
Methods:A total of 95 pts (aged ≥18 yrs, ECOG PS 0 or 1) with mTNBC previously treated with ≤2 prior lines of chemotherapy for metastatic disease will be enrolled. Phase 1b included a safety run-in cohort in which ≥6 pts received intravenous (IV) eribulin mesylate 1.4 mg/m2 on day (d) 1 and d8 and IV pembrolizumab 200 mg on d1 of a 21-d cycle. Dose-limiting toxicity (DLT) of the combination regimen were assessed in the first cycle to determine the recommended phase 2 dose (RP2D). In phase 2, patients were enrolled in 2 cohorts according to receipt of prior chemotherapy in the metastatic setting (0 vs 1–2 prior lines). Primary endpoints were determination of safety and tolerability (phase 1b) and evaluation of objective response rate (phase 2); secondary endpoints included evaluation of progression-free survival, overall survival, and duration of response.
Results:We report an interim analysis of the first 39 enrolled pts (n=7, phase 1b; n=32, phase 2). No DLTs were observed in phase 1b. The RP2D was defined as eribulin 1.4 mg/m2 on d1 and d8 and pembrolizumab 200 mg on d1 of a 21-d cycle. As of data cut-off (May 16, 2016), the most frequent adverse events (AEs; all grades) were fatigue (69%), nausea (51%), alopecia (36%), neutropenia (36%), and peripheral neuropathy (28%). The most frequent AEs of grade 3 or 4 were neutropenia (31%) and fatigue (8%). Serious AEs (all nonfatal) occurred in 36% of pts and AEs leading to dose adjustment were observed in 56% of pts. Objective responses, including a complete response, by investigator assessment were observed during this interim analysis, and will be presented at the meeting.
Conclusions: The combination of eribulin with pembrolizumab represents a novel treatment regimen in pts with mTNBC. AEs observed with the combination were comparable to those observed with either treatment as monotherapy.
Clinical Trials.gov: NCT02513472.
Citation Format: Tolaney S, Savulsky C, Aktan G, Xing D, Almonte A, Karantza V, Diab S. Phase 1b/2 study to evaluate eribulin mesylate in combination with pembrolizumab in patients with metastatic triple-negative breast cancer [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 P5-15-02.