Results of a phase Ib study investigating durvalumab in combination with eribulin in patients with metastatic HER2-negative breast cancer and recurrent ovarian cancer.

Abstract

e15120 Background: The release of tumor-associated antigens with cytotoxic chemotherapy treatment may enhance the response to immune checkpoint blockade. Eribulin is a novel microtubule inhibitor with proven overall survival (OS) benefit in metastatic breast cancer (MBC), which may also enhance intratumoral vascular remodeling. Durvalumab, a humanized monoclonal antibody, targets the programmed cell death ligand-1 (PD-L1) receptor. This study sought to determine the recommended phase II dose (RP2D) of eribulin in combination with durvalumab, as well as the safety and preliminary anti-tumor activity of the combination in patients with previously treated HER2-negative MBC and recurrent ovarian cancer (ROC). Methods: Cohorts of 3-6 patients with HER2-negative MBC and ROC were treated in a modified 3+3 design. Eligible patients received escalating doses of eribulin (1.1mg/m2 or 1.4 mg/m2 IV on day 1 and day 8) with durvalumab (1.12g IV on day 1) in 21-day cycles until dose-limiting toxicity (DLT), intolerable adverse events (AEs), disease progression, or other reasons for withdrawal. Primary endpoint: the rate of dose limiting toxicities (DLTs) during cycle 1 and 2 of therapy. Secondary endpoints: AE rate, Objective Response Rate (ORR), progression-free survival (PFS), and OS. Results: Nine patients [median age 63 (37-77)] with median 4 prior therapies for advanced disease were treated: 5 patients with HER2-negative MBC and 4 patients with ROC. The RP2D of eribulin was 1.4mg/m2 in combination with durvalumab. There were no DLTs experienced during the first two cycles of therapy. The most common treatment-related AEs ( > 50%) were fatigue, neutropenia, decreased white blood cell count, anemia, AST and alkaline phosphatase elevation, hyperglycemia, and nausea; most were grade 1/2. There was one immune-related AE of grade ≥3 (hepatitis). Three patients discontinued study drug related to toxicity [neutropenia (n = 1), hepatic toxicity (n = 2)]. ORR was 55% (all partial response) and 4 additional patients experienced stable disease; all MBC patients experienced a response to therapy. Median PFS was 6.2 months. Median OS has not been reached. Conclusions: The combination of eribulin and durvalumab had a favorable AE profile in patients with previously treated HER2- MBC and ROC. The early anti-tumor activity observed in this study suggests that further investigation of this combination is warranted. Clinical trial information: NCT03430518 .