1466P - Napabucasin + nab-paclitaxel with gemcitabine in patients (pts) with metastatic pancreatic adenocarcinoma (mPDAC): Results from the phase III CanStem111P study

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

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, PanCan and 1Globe. T. Okusaka: Financial Interests, Personal and Institutional, Research Grant: Esai; Financial Interests, Personal, Advisory Board: Esai; Financial Interests, Personal, Speaker’s Bureau: Esai; Financial Interests, Personal and Institutional, Research Grant: Novartis; Financial Interests, Personal, Speaker’s Bureau: Novartis; Financial Interests, Personal and Institutional, Research Grant: Eli Lily; Financial Interests, Personal, Speaker’s Bureau: Eli Lily; Financial Interests, Personal and Institutional, Research Grant: Dainippon Sumitomo; Financial Interests, Personal, Advisory Board: Dainippon Sumitomo; Financial Interests, Personal, Speaker’s Bureau: Dainippon Sumitomo; Financial Interests, Personal and Institutional, Research Grant: AstraZeneca; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal and Institutional, Research Grant: Chugai; Financial Interests, Personal, Speaker’s Bureau: Chugai; Financial Interests, Personal and Institutional, Research Grant: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb; Financial Interests, Personal, Speaker’s Bureau: Bristol-Myers Squibb; Financial Interests, Personal and Institutional, Research Grant: MSD; Financial Interests, Personal, Speaker’s Bureau: MSD; Financial Interests, Personal and Institutional, Research Grant: Baxter; Financial Interests, Personal and Institutional, Research Grant: Taiho; Financial Interests, Personal, Speaker’s Bureau: Taiho; Financial Interests, Personal, Advisory Board: Nihon Servier; Financial Interests, Personal, Speaker’s Bureau: Nihon Servier; Financial Interests, Personal, Speaker’s Bureau: Ono; Financial Interests, Personal, Speaker’s Bureau: Yakult Honsha; Financial Interests, Personal, Speaker’s Bureau: Daiichi Sankyo; Financial Interests, Personal, Speaker’s Bureau: Nippon Shinyaku; Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Personal, Speaker’s Bureau: Mundipharma. D. Oh: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Genentech/Roche; Financial Interests, Personal, Advisory Board: Merck Serono; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Taiho; Financial Interests, Personal, Advisory Board: ASLAN; Financial Interests, Personal, Advisory Board: Halozyme; Financial Interests, Personal, Advisory Board: Zymeworks; Financial Interests, Personal, Advisory Board: BMS/Celgene; Financial Interests, Personal, Advisory Board: BeiGene; Financial Interests, Personal, Advisory Board: Basilea; Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Research Grant: Novartis; Financial Interests, Personal, Research Grant: Array; Financial Interests, Personal, Research Grant: Eli Lilly; Financial Interests, Personal, Research Grant: Servier; Financial Interests, Personal, Research Grant: BeiGene; Financial Interests, Personal, Research Grant: MSD; Financial Interests, Personal, Research Grant: Handok. M. Ueno: Financial Interests, Personal, Invited Speaker: Taiho Pharmaceutical, Yakult Honsha, AstraZeneca, Merck Biopharma, Eisai, MSD, Servier, Chugai Pharma; Financial Interests, Institutional, Research Grant: Astellas Pharma, Taiho Pharmaceutical, Eisai, AstraZeneca, Ono Pharmaceutical, MSD, Merck Biopharma, Incyte, Chugai Pharma. T. Ioka: Financial Interests, Personal, Speaker’s Bureau: Taiho Pharmaceutical; Financial Interests, Personal, Advisory Role: Taiho Pharmaceutical; Financial Interests, Institutional, Research Grant: AstraZeneca; Non-Financial Interests, Personal, Advisory Board: Incyte; Financial Interests, Institutional, Research Grant: Incyte; Financial Interests, Invited Speaker: Eisai; Financial Interests, Invited Speaker: Astellas. M.S. Noel: Financial Interests, Personal, Invited Speaker: Daiichi Sankyo. M. Reni: Financial Interests, Personal, Advisory Board: Eli-Lily; Financial Interests, Personal, Advisory Board: Celgene; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Shire; Financial Interests, Personal, Advisory Board: Baxter; Financial Interests, Personal, Advisory Board: Servier; Financial Interests, Personal, Advisory Board: MSD. J. Tabernero: Financial Interests, Personal, Advisory Board, Consultancy role: Array BioPharma; Financial Interests, Personal, Advisory Board, Consultancy role: AstraZeneca; Financial Interests, Personal, Advisory Board, Consultancy role: Avvinity; Financial Interests, Personal, Advisory Board, Consultancy role: Bayer; Financial Interests, Personal, Advisory Board, Consultancy role: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board, Consultancy role: Chugai; Financial Interests, Personal, Advisory Board, Consultancy role: Daiichi Sankyo; Financial Interests, Personal, Advisory Board, Consultancy role: F. Hoffman-La Roche; Financial Interests, Personal, Advisory Board, Consultancy role: Genentech; Financial Interests, Personal, Advisory Board, Consultancy role: HalioDX; Financial Interests, Personal, Advisory Board, Consultancy role: Hutchinson; Financial Interests, Personal, Advisory Board, Consultancy role: Ikena Oncology; Financial Interests, Personal, Advisory Board, Consultancy role: IQVIA; Financial Interests, Personal, Advisory Board, Consultancy role: Lily; Financial Interests, Personal, Advisory Board, Consultancy role: Menarini; Financial Interests, Personal, Advisory Board, Consultancy role: Merck Serono; Financial Interests, Personal, Advisory Board, Consultancy role: Merus; Financial Interests, Personal, Advisory Board, Consultancy role: MSD; Financial Interests, Personal, Advisory Board, Consultancy role: Mirati; Financial Interests, Personal, Advisory Board, Consultancy role: Neophore; Financial Interests, Personal, Advisory Board, Consultancy role: Novartis; Financial Interests, Personal, Advisory Board, Consultancy role: Orion Biotechnology; Financial Interests, Personal, Advisory Board, Consultancy role: Peptomyc; Financial Interests, Personal, Advisory Board, Consultancy role: Pfizer; Financial Interests, Personal, Advisory Board, Consultancy role: Pierre Fabre; Financial Interests, Personal, Advisory Board, Consultancy role: Samsung Biologics; Financial Interests, Personal, Advisory Board, Consultancy role: Sanofi; Financial Interests, Personal, Advisory Board, Consultancy role: Seattle Genetics; Financial Interests, Personal, Advisory Board, Consultancy role: Servier; Financial Interests, Personal, Advisory Board, Consultancy role: Taiho; Financial Interests, Personal, Advisory Board, Consultancy role: Tessa Therapeutics; Financial Interests, Personal, Advisory Board, Consultancy role: Theramyc. J. Li: Other, Institutional, Full or part-time Employment: SDP Oncology. E. Foos: Financial Interests, Personal, Full or part-time Employment, Former employee: Sumitomo Dainippon Pharma Oncology, Inc. C. Oh: Financial Interests, Personal, Full or part-time Employment: Sumitomo Dainippon Pharma Oncology, Inc. E. Van Cutsem: Financial Interests, Personal, Advisory Board: Array, Astellas, Astrazeneca, Bayer, Beigene, Biocartis, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Daiichi, Halozyme, GSK, Incyte, Ipsen, Lilly, Merck Sharp & Dohme, Merck KGaA, Novartis, Pierre Fabre, Roche, Servier, Sirtex, and Taiho; Financial Interests, Institutional, Research Grant: Amgen, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Ipsen, Lilly, Merck Sharp & Dohme, Merck KGaA, Novartis, Roche, and Servier. All other authors have declared no conflicts of interest.