A phase Ib/II study of BBI608 combined with weekly paclitaxel in advanced pancreatic cancer.

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 #A6
J Clin Oncol 34, 2016 (suppl 4S; abstr 196)
Tanios S. Bekaii-Saab, Sameh Mikhail, Adrian Langleben, Carlos Becerra, Derek J. Jonker, Timothy R. Asmis, Gregory Michael Cote, Christina Sing-Ying Wu, Eunice Lee Kwak, Alexander I. Spira, Fadi S. Braiteh, Stephen Lane Richey, Stephanie Hume, Matthew Hitron, Chiang Li; The Ohio State University Comprehensive Cancer Center, James Cancer Hospital, Solove Research Institute, Columbus, OH; St. Mary's Hospital, Westmount, QC, Canada; Texas Oncology, Baylor Sammons Cancer Center, Dallas, TX; Ottawa Hospital Cancer Centre, Ottawa, ON, Canada; Massachusetts General Hospital, Boston, MA; The Ohio State University Comprehensive Cancer Center, Arthur G. James Cancer Hospital, Richard J. Solove Research Institute, Columbus, OH; Massachusetts General Hospital Cancer Center, Boston, MA; Virginia Cancer Specialists Research Institute, US Oncology Research, Fairfax, VA; The US Oncology Network, McKesson Specialty Health, The Woodlands, TX; Texas Oncology, The US Oncology Network, McKesson Specialty Health, Fort Worth, TX; Boston Biomedical, Inc., Cambridge, MA

Abstract Disclosures


Background: Cancer stemness is thought to be associated with resistance to chemotherapies. BBI608, a first-in-class cancer stemness inhibitor that works through inhibiting the Stat3 pathway, has shown potent synergistic anti-tumor activity with paclitaxel in vivo. In a phase Ib dose escalation study in patients with advanced solid tumors, BBI608 plus weekly paclitaxel was well tolerated and a RP2D of BBI608 480 mg BID was determined. Methods: Patients with heavily pretreated metastatic pancreatic adenocarcinoma were enrolled in a phase Ib/II extension study to assess safety, tolerability, and preliminary anti-cancer activity in patients with this diagnosis. BBI608 was administered orally at a starting dose of 480 mg or 500 mg twice daily along with paclitaxel 80 mg/m2 IV weekly 3 of every 4 weeks. A sample size of 40 set the bounds of the 90% CI at ±10% to 14%, assuming a DCR of 60% to 80%. Safety and efficacy results for the cohort will be presented as late breaking data. Results: 41 patients were enrolled. Patients had received a median of 2 prior lines of treatment including FOLFIRINOX (71%), gemcitabine/nab-paclitaxel (44%), or both (37%). Overall, prior therapy included gemcitabine in 90%, a thymidylate synthetase inhibitor (eg 5FU, capecitabine) in 81%, platinum in 76%, irinotecan in 73%, and taxane in 44%. Protocol therapy was well tolerated. Related grade 3 AE included diarrhea (N = 2, 4.9%), abdominal pain (N = 2, 4.9%), and nausea (N = 1, 2.4%), and were rapidly reversible. For evaluable patients (N = 31), response rate (PR+CR) was 7% and disease control rate (SD+PR+CR) was 52%. In evaluable taxane-naïve patients (N = 19), response rate was 11%, disease control rate was 63%, and 16% were progression free at 24 weeks. Overall (ITT, N = 41) mPFS was 10 weeks and mOS was 24 weeks. For the taxane-naïve patients (ITT, N = 23) mPFS was 16 weeks and mOS was 30 weeks. Conclusions: BBI608 plus weekly paclitaxel has demonstrated safety, tolerability, and promising activity in patients with refractory, heavily pretreated pancreatic cancer; particularly in taxane-naïve patients. Durable disease control and prolonged overall survival in this pre-treated population are notable. Clinical trial information: NCT01325441