A phase Ib study of cancer stem cell (CSC) pathway inhibitor BBI-608 in combination with gemcitabine and nab-paclitaxel (nab-PTX) in patients (pts) with metastatic pancreatic ductal adenocarcinoma (mPDAC).

Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract
Session Type and Session Title: 
Poster Session B: Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract
Abstract Number: 


Poster Board Number: 
Poster Session B Board #E8
J Clin Oncol 34, 2016 (suppl 4S; abstr 284)
Safi Shahda, Bassel F. El-Rayes, Bert H. O'Neil, Alexander Starodub, Wahid Tewfik Hanna, Laura Borodyansky, Cindy Oh, Chiang Li, Tanios S. Bekaii-Saab; Indiana University, Indianapolis, IN; Winship Cancer Institute of Emory University, Atlanta, GA; Indiana University Health University Hospital, Indianapolis, IN; Indiana University Health Goshen Center for Cancer Care, Goshen, IN; University of Tennessee Medical Center, Knoxville, TN; Boston Biomedical, Inc., Cambridge, MA; The Ohio State University Comprehensive Cancer Center, Columbus, OH

Abstract Disclosures


Background: BBI-608 is an oral first-in-class cancer stemness inhibitor that works by blocking STAT3-mediated transcription of cancer stemness genes. Potent anti-CSC activity was observed in vitro and in vivo, in mono- and combination therapy. In phase I studies, BBI-608 was generally well tolerated with encouraging signs of anti-tumor activity. Methods: A phase Ib open label, multi-center study in pts with mPDAC was performed to determine RP2D, safety, tolerability, and preliminary anti-cancer activity of BBI-608 in combination with Gemcitabine and nab-PTX. BBI-608 was administered at 240 mg BID in combination with Gemcitabine 125 mg/m2 and nab-PTX 1000 mg/m2administered weekly for 3 out every 4 weeks until progression of disease, unacceptable toxicity, or other discontinuation criterion was met. Results: 31 pts were enrolled and received BBI-608 in combination with Gemcitabine and nab-PTX for a total sum of 83 study cycles. 25 of 31 pts (80.6%) were treatment-naïve and 6 pts (19.4%) received 1 prior line of systemic therapy. Most common adverse events included grade 1 diarrhea, abdominal pain, nausea, and fatigue. Combination treatment was well tolerated with no dose-limiting toxicity observed and safety profile similar to that of each agent individually. One patient experienced grade 3 event of dehydration related to protocol therapy which resolved with hydration. Of the 8 pts enrolled in the RP2D determination portion of the study, 7 pts were evaluable for response with disease control (PR + SD) was observed in 7/7 pts (100%). Tumor regression was observed in 6/7 (85.7%) with 3 PR (41.3%, 37.6% and 33.3% regression) and 3 SD (25.8%, 21.1%, and 19.9% regression). The median progression free survival was 7.8 months with PR or SD of > 6 months in 6/8 pts (75%). Conclusions: This phase Ib study demonstrated that BBI-608 at 240 mg BID can be safely combined with Gemcitabine and nab-PTX. Encouraging anti-tumor activity with durable response was observed in pts with mPDAC. Clinical trial information: NCT02231723