Napabucasin plus nab-paclitaxel with gemcitabine in patients (pts) with metastatic pancreatic adenocarcinoma (mPDAC): Results from the phase III CanStem111P study

Abstract

Background We present results from CanStem111P, an open-label phase III study of napabucasin + nab-paclitaxel (P) and gemcitabine (G) vs P+G in pts with mPDAC (NCT02993731).

Methods Adults with histologically or cytologically confirmed treatment-naive mPDAC were randomized 1:1 to napabucasin (240 mg oral twice daily, continuously, each 28-day [D] cycle) + P (125 mg/m2 IV) + G (1000 mg/m2 IV) (napabucasin arm) or P+G (control arm [CTL]); P+G given on D1, 8, and 15 of 28-D cycles). Primary endpoint: overall survival (OS) in the general study population (GSP; all randomized pts). Secondary endpoints: progression-free survival (PFS) in the GSP, and objective response rate (ORR) and disease control rate (DCR) in the response analysis set (RAS). Exploratory endpoint: OS in the phosphorylated signal transducer and activator of transcription 3 (pSTAT3) biomarker-positive (BM+) subgroup (per pSTAT3 immunohistochemistry D3A7 assay; Agilent Technologies, Inc).

Results In the GSP (n=565 napabucasin; n=569 CTL), 34% of pts were BM+ (n=206 napabucasin; n=176 CTL). Median (m) OS, mPFS, ORR, and DCR were similar between treatment arms in the GSP (mOS; mPFS), RAS (ORR; DCR), and BM+ subgroup (Table). Adverse events (AEs) were reported in 99.8% (napabucasin) and 99.3% (CTL) of the GSP. Grade ≥3 AEs were 85.4% and 83.9%, with a higher incidence of gastrointestinal-related events with napabucasin vs CTL (diarrhea: 11.6% vs 4.9%; abdominal pain: 10.0% vs 4.8%).

Conclusions In mPDAC in the first-line setting, napabucasin added to P+G did not improve OS, PFS, ORR, or DCR in the GSP (OS; PFS), RAS (ORR; DCR) or BM+ subgroup. AEs were consistent with previously published data. Our trial represents the largest experience in pts with mPDAC receiving P+G. Our study suggests longer mOS and higher ORR rates than previously reported for P+G. The outcomes in P+G–treated pts with mPDAC reinforces the value of this doublet combination as a platform for future novel approaches. Table: 1466P.

GSP BM+ Napabucasin (n=565) CTL (n=569) Napabucasin (n=206) CTL (n=176) mOS, mo 11.43b 11.73c 11.40 10.78 HR (p-valuea) 1.07 (p=0.84) 0.97 (p=0.79) mPFS, mo 6.70d 6.08e 5.68 5.82 HR (p-valuea) 1.04 (p=0.71) 1.09 (p=0.45)f ORRg, % 43 43 42 47 95% CI 39, 47 39, 47 35, 49 40, 55 DCRg, % 74 76 75 79 95% CI 71, 78 72, 80 69, 81 72, 84 OS, summarized via Kaplan-Meier, compared treatment arms (stratified [GSP]; unstratified [BM+ subgroup] log-rank tests). a1-sided: GSP napabucasin vs CTL; 2-sided: BM+ napabucasin vs CTL. Follow-up (mo): b11.4, c11.7, d6.7, e6.1. f2-sided. gGSP RAS n=556 napabucasin, n=559 CTL; BM+ RAS n=203 napabucasin, n=173 CTL. CI, confidence interval; HR, hazard ratio; mo, months.

Clinical trial identification NCT02993731.

Editorial acknowledgement Medical writing support was provided by Stella Chow, PhD, of Ashfield MedComms, an Ashfield Health company.

Legal entity responsible for the study Sumitomo Dainippon Pharma Oncology, Inc.

Funding This study was supported by Sumitomo Dainippon Pharma Oncology, Inc.

Disclosure T. Bekaii-Saab: Financial Interests, Institutional, Research Grant: Agios, Arys, Arcus, Atreca, Boston Biomedical, Bayer, Amgen, Merck, Celgene, Lilly, Ipsen, Clovis, Seattle Genetics, Genentech, Novartis, Mirati, Merus, Abgenomics, Incyte, Pfizer, BMS; Financial Interests, Institutional, Other, Consulting: Ipsen, Array Biopharma, Pfizer, Seattle Genetics, Bayer, Genentech, Incyte and Merck; Financial Interests, Personal, Other, Consulting: AbbVie, Boehringer Ingelheim, Janssen, Eisai, Daichii Sankyo, Natera, TreosBio, Celularity, Exact Science, Sobi, Beigene, Xilis, AstraZeneca andFoundation Medicine; Financial Interests, Personal, Advisory Board: Imugene, Immuneering and Sun Biopharma; Financial Interests, Personal, Other, Inventions/Patents: WO/2018/183488 and WO/2019/055687; Financial Interests, Personal, Other, Independent data monitoring committee (IDMC) Data and safety monitoring board (DSMB): AstraZeneca, Exelixis, Lilly, PanC