CanStem111P trial: A Phase 3 Study of napabucasin (NAPA) plus nab-paclitaxel (nPTX) with gemcitabine (Gem) in adult patients with metastatic pancreatic adenocarcinoma (mPDAC) - Trial in progress

Abstract

Introduction: NAPA is an oral investigational agent, which has been hypothesized to inhibit cancer stemness pathways, including STAT3 pathway implicated in cancer stem‐cell viability. Preclinical studies suggest that NAPA may sensitize heterogeneous cancer cells to chemotherapeutic agents, including nPTX and Gem. Encouraging anticancer activity in mPDAC was observed in a phase 1b study (NCT02231723) of 59 patients (pts), reporting 92% (46/50) disease control rate (DCR) and 56% (28/50) overall response rate (ORR), with 2 complete and 26 partial responses in pts who had a RECIST evaluation. Maturing median progression‐free survival (mPFS) and median overall survival (mOS) were 7.06 and 9.59 mo, respectively. On the basis of these data, a phase 3 trial is being conducted in North America, Europe, Australia and Asia. Methods: This randomized, open‐label, multicenter study (NCT02993731) will assess the efficacy of NAPA +nPTX+ Gem vs nPTX+ Gem in pts with mPDAC (n=1132). Pts must not have received systemic treatment for mPDAC. Pts will be randomized in a 1:1 ratio to receive NAPA 240mg PO twice daily continuously plus IV nPTX 125mg/m 2+ Gem 1000mg/m 2 weekly for 3 of every 4 weeks or nPTX + Gem weekly for 3 of every 4 weeks. Pts will be stratified by geography, Eastern Cooperative Oncology Group performance status, and presence of liver metastases. Treatment will continue until disease progression or another discontinuation criterion. The primary endpoint is OS in the general study population (HR 0.80 for OS improvement from 8.5 to 10.63 months); secondary endpoints include ORR, DCR, and PFS. In addition, OS, PFS, ORR, and DCR will be evaluated in the biomarker positive sub‐population. Study enrollment is ongoing with >30% of patients enrolled to date.