Abstract OT1-01-07: nab-paclitaxel (nab-P) plus nivolumab (Nivo) in human epidermal growth factor receptor 2 (HER2)–negative recurrent metastatic breast cancer (MBC)
Authors: Waterhouse D , Gutierrez M , Bekaii-Saab T , DeRosa W , Wainberg Z , George B , Duval Fraser C , Ko A , Pierce DW , Stergiopoulos S , Soliman H 
Published: May 2016

Abstract
Background: Nivo is an inhibitory antibody against programmed death receptor-1 (PD-1), a regulator of antitumor immunity. Nivo is approved for treatment of unresectable or metastatic melanoma and disease progression (PD) following ipilimumab or, in BRAF V600 mutation–positive melanoma, following a BRAF inhibitor, and for metastatic squamous non-small cell lung cancer (NSCLC) following PD during or after platinum-based chemotherapy. Nivo and other immune checkpoint inhibitors are also being investigated in other tumor-types. nab-P is a novel taxane formulation and does not require prophylaxis with immunosuppressive steroids. It has demonstrated superior efficacy over control regimens in phase III studies of MBC, pancreatic cancer, and NSCLC. This open-label, 6-arm, multicenter phase I trial will evaluate the safety of Nivo with nab-P in 3 cancer types (2 arms/disease): MBC, advanced NSCLC (+ carboplatin), and advanced pancreatic cancer (± gemcitabine). The study design for the MBC portion is described below.
Methods: Eligibility criteria include histologically/cytologically confirmed HER2-negative MBC; 1 prior chemotherapy for MBC, including an anthracycline unless clinically contraindicated; no relapse &lt; 12 months after taxane adjuvant therapy; measurable disease by RECIST v1.1; ECOG performance status 0-1; adequate organ function; and preexisting peripheral neuropathy grade &lt; 2. Patients (pts) with MBC will be treated in 2 arms: nab-P 100 mg/m2 on days 1, 8, and 15 of each 28-day cycle plus Nivo 3 mg/kg on days 1 and 15 starting at cycle 3 or nab-P 260 mg/m2 on day 1 of each 21-day cycle plus Nivo 5 mg/kg on day 15 starting at cycle 3. Pts will be treated until PD or allowed to continue treatment beyond RECIST v1.1–defined PD if they continue to meet study eligibility; do not have rapid PD or clinical deterioration or unacceptable toxicities; and can benefit from continuation of study treatment in the treating physician's opinion and will not delay an imminent intervention to prevent serious complications of PD. The primary endpoints of the study are the number of pts with dose-limiting toxicities (DLTs) in each treatment arm (part 1) and the percentage of pts with grade 3/4 treatment-emergent adverse events (TEAEs) or treatment discontinuation due to a TEAE (parts 1 and 2). Part 1 of the study will assess whether the starting dose of Nivo is deemed safe (≤ 1 DLT in 6 pts); otherwise, the Nivo dose will be de-escalated and assessed in a new cohort at the next lower dose level. The Nivo dose in combination with nab-P deemed safe in a treatment arm may be further assessed in part 2 of the study, with enrollment expanded to an additional ∼ 14 pts/arm (total of 20 Nivo-treated pts/arm). Secondary study endpoints include TEAEs leading to dose reduction, delay, interruption, or treatment discontinuation; progression-free survival; overall survival; disease control rate; overall response rate; and duration of response (per RECIST v1.1). Exploratory endpoints include tumor-associated PD-L1 expression, modulation of immune activation in the tumor and peripheral blood in response to Nivo treatment, Nivo serum levels, and development of anti-globulin antibodies. ClinicalTrials.gov identifier NCT02309177.
Citation Format: Waterhouse D, Gutierrez M, Bekaii-Saab T, DeRosa W, Wainberg Z, George B, Duval Fraser C, Ko A, Pierce DW, Stergiopoulos S, Soliman H. nab-paclitaxel (nab-P) plus nivolumab (Nivo) in human epidermal growth factor receptor 2 (HER2)–negative recurrent metastatic breast cancer (MBC). [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr OT1-01-07.