Disease	Breast cancer
Stage of Disease/Treatment	Metastatic/advanced
Prior Therapy	No designated number of regimens
Type of Study	Phase I, 3+3
Primary Endpoint	Maximum tolerated dose
Secondary Endpoints	Safety, tolerability, pharmacodynamics, correlative endpoint, efficacy
Additional Details of Endpoints or Study Design
Eligibility criteria: Patients were required to be postmenopausal with histologically confirmed ER‐positive, HER2‐negative metastatic or locally advanced breast cancer. Patients were required to have a favorable performance status (ECOG 0–1) without significant hematologic, hepatic, and renal impairment as measured by laboratory measurements, as well as cancer that was progressing by RECIST 1.1 criteria while taking fulvestrant for ≥56 days as the most recent line of treatment.
Adverse event severity was graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. Dose‐limiting toxicity was defined as any grade 3 or higher nonhematologic toxicity or any grade 4 or higher hematologic toxicity during cycle 1 that was considered related to ixazomib.
Safety (adverse events and hematological/chemistry laboratory parameters) and physical status (including ECOG performance status) were assessed at baseline and at the end of each 21‐day cycle. Adverse event severity was graded using the NCI CTCAE version 4.03. Dose‐limiting toxicity was defined as any grade 3 or higher nonhematologic toxicity or any grade 4 or higher hematologic toxicity during cycle 1 that was considered related to ixazomib. All patients underwent computed tomography (CT) scanning of the chest, abdomen, and pelvis and a bone scan, or a positron emission tomography‐CT scan within 21 days of study entry. Disease reassessments were repeated with the same imaging modality approximately every 6 weeks on study. All lesions measurable by radiologic study or physical exam, up to a maximum of five, were identified as “target lesions” and measured at baseline and after each imaging session. Tumor response was assessed per RECIST criteria v1.1. Clinical benefit was defined as complete response, partial response, or stable disease for ≥24 weeks. PFS was calculated. PFS ratio was then calculated as (PFS on ixazomib + fulvestrant)/(PFS on prior line of fulvestrant).
Investigator's Analysis	Active and should be pursued further