A Phase Ib Trial of Durvalumab in Combination with Trastuzumab in HER2‐Positive Metastatic Breast Cancer (CCTG IND.229)

AbstractBackground.Immune checkpoint inhibitors are active in a broad range of cancers, including programmed death ligand 1 (PD‐L1)‐positive, triple‐negative, metastatic breast cancer (MBC). Antibody‐dependent cell‐mediated cytotoxicity is a mechanism of action of trastuzumab. We performed a phase Ib trial of durvalumab and trastuzumab in HER2‐positive MBC previously treated with chemotherapy and anti‐HER2 antibodies to assess safety, efficacy, and correlative endpoints.Patients and Methods.Patients with HER2‐positive MBC were enrolled on a standard 3 + 3 design. Dose level 1 was durvalumab (1,125 mg intravenously day 1) and trastuzumab (8 mg/kg intravenously loading, then 6 mg/kg day 1) on a q3 weekly cycle. An expansion cohort at the recommended phase II dose (RP2D) performed tumor biopsies at baseline and after cycle 1. The primary endpoint was to establish the RP2D.Results.Fifteen patients were accrued from April to December 2016, of which 14 were evaluable for response. Median age was 54 years (range 40–86); the majority had visceral disease (87%) and at least three prior (adjuvant and/or metastatic) lines of chemotherapy (73%), including trastuzumab (93%), pertuzumab (60%), and trastuzumab‐emtansine (93%) for MBC. No dose‐limiting toxicities were observed at dose level 1 (n = 6) or dose expansion (n = 9) during cycle 1. One patient developed a grade ≥3 immune‐related adverse event (grade 4 diabetes mellitus). No responses by RECIST were seen, w...
Source: The Oncologist - Category: Cancer & Oncology Authors: Tags: Breast Cancer Source Type: research