Results from a Phase I Study of Andecaliximab in Combination with Paclitaxel in Patients with Previously Untreated Metastatic Breast Cancer.

1032 Background: Matrix metalloproteinase-9 (MMP-9) is highly expressed in several advanced cancers, including metastatic breast cancer, and confers an adverse prognosis. In a preclinical breast cancer model, inhibition of MMP-9 was demonstrated with tumor growth inhibition. Andecaliximab (ADX) is a chimeric antibody directed against MMP-9, engineered to remove T cell epitopes and reduce risk of immunogenicity. In this phase I multi-cohort study, we hypothesized that the combination of ADX with standard of care chemotherapy (paclitaxel) should be safe and tolerable, and demonstrate clinical activity in patients with previously untreated metastatic breast cancer. (Clinicaltrials.gov NCT# 01803282) Methods: We enrolled 15 eligible (13 female) patients with radiographically measurable disease and previously untreated metastatic breast cancer. The median age was 59 years (range 23-81). Patients were treated with 800 mg ADX IV every 2 weeks + paclitaxel (80mg/m2 on days 1, 8, and 15 of a 28-day cycle). The primary endpoints of this study were safety and tolerability. Exploratory endpoints were investigator assessed objective response rate (ORR), progression free survival (PFS), and overall survival (OS). Results: As of September 22, 2017, the median ADX treatment duration for this study was 5.3 months. The most common adverse events were alopecia (60%), fatigue (60%), constipation (47%), neutropenia (40%), diarrhea (33%), and nausea (33%). Serious adverse events (SAEs) were reported in 33% of patients. The most common SAEs were acute kidney injury and atrial fibrillation (7% each). The median PFS was 7.4 months (90% CI 5.3-8.6 months) and the overall response rate was 53% (95%CI 30-76%) with 7% complete response rate. The median OS was not reached at the time. Study treatment continues in 27% of patients. Conclusions: Combination of ADX with paclitaxel was safe and effective in first-line treatment of patients with metastatic breast cancer. Updated data will be presented at the time of the meeting. Clinical trial information: NCT01803282.