CanStem303C trial: A phase III study of BBI-608 (napabucasin) in combination with 5-fluorouracil (5-FU), leucovorin, irinotecan (FOLFIRI) in adult patients with previously treated metastatic colorectal cancer (mCRC)

Background

BBI-608 (aka napabucasin) is an orally-administered first-in-class cancer stemness inhibitor. By targeting Stat3, BBI-608 blocks cancer stem cell (CSC) self-renewal and survival through suppressing stemness pathways as well as immune evasion. Potent anti-CSC and anti-metastatic activity was observed in preclinical models, with strong synergy between BBI-608 and 5-FU or irinotecan. Moreover, expression of cancer stemness genes stat3 and �-catenin, poor prognostic biomarkers in many cancer types, predict sensitivity to BBI-608. Encouraging anticancer activity in advanced CRC was observed in a phase Ib (O'Neil et al, ASCO 2016) study including 46 pts. On the basis of these data, a phase III trial is being conducted in North America, Europe, Australia, and Asia.

Trial design

This study (ClinicalTrials.gov NCT02753127) will assess the efficacy of BBI-608 + FOLFIRI vs FOLFIRI in pts with mCRC (n = 1250). Addition of bevacizumab (bev) to the FOLFIRI regimen, per investigator choice, will be permissible. Pts must have failed one prior line of therapy containing bev, oxaliplatin, and a fluoropyrimidine for metastatic disease. Pts are randomized in a 1:1 ratio to receive BBI-608 240 mg twice daily continuously plus standard FOLFIRI IV, bi-weekly, or standard FOLFIRI IV, bi-weekly alone. If Investigator elects, pts will receive bev prior to FOLFIRI infusion. Treatment will continue until disease progression, death, intolerable toxicity, or patient/investigator decision to stop. Primary endpoint is overall survival (OS) in the general study population (HR 0.80 for OS improvement from 12.54 to 15.68 months); secondary endpoints include OS in the biomarker positive population, progression free survival (PFS) in general study population, PFS in biomarker positive population, overall response rate and disease control rate in the general study population and in biomarker positive population, safety and quality of life. In addition, blood and tumor archival tissue will be assessed for pharmacokinetic and biomarker analyses. As of May 11, 2016, study recruitment process is active.

Clinical trial identification

ClinicalTrials.gov NCT02753127

Legal entity responsible for the study

Boston Biomedical, Inc.

Funding

Boston Biomedical, Inc.

Disclosure

L. Borodyansky: Employee at Boston Biomedical, Inc. C.J. Li: CMO at Boston Biomedical, Inc. Stock ownership and Member of Advisory Board and Board of Directors. All other authors have declared no conflicts of interest.