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Clinical Trial
. 2018 Nov;119(10):1208-1214.
doi: 10.1038/s41416-018-0246-z. Epub 2018 Oct 15.

Galunisertib plus gemcitabine vs. gemcitabine for first-line treatment of patients with unresectable pancreatic cancer

Davide Melisi  1 , Rocio Garcia-Carbonero  2 , Teresa Macarulla  3 , Denis Pezet  4 , Gael Deplanque  5 , Martin Fuchs  6 , Jorg Trojan  7 , Helmut Oettle  8 , Mark Kozloff  9 , Ann Cleverly  10 , Claire Smith  11 , Shawn T Estrem  12 , Ivelina Gueorguieva  10 , Michael M F Lahn  13 , Al Blunt  14 , Karim A Benhadji  15 , Josep Tabernero  16
Affiliations
Clinical Trial

Galunisertib plus gemcitabine vs. gemcitabine for first-line treatment of patients with unresectable pancreatic cancer

Davide Melisi et al. Br J Cancer. 2018 Nov.

Abstract

Background: Galunisertib is the first-in-class, first-in-human, oral small-molecule type I transforming growth factor-beta receptor (ALK5) serine/threonine kinase inhibitor to enter clinical development VSports手机版. The effect of galunisertib vs. placebo in patients with unresectable pancreatic cancer was determined. .

Methods: This was a two-part, multinational study: phase 1b was a non-randomised, open-label, multicentre, and dose-escalation study; phase 2 was a randomised, placebo- and Bayesian-augmented controlled, double-blind study in patients with locally advanced or metastatic pancreatic adenocarcinoma considered candidates for first-line chemotherapy with gemcitabine. Patients were randomised 2:1 to galunisertib-gemcitabine (N = 104) or placebo-gemcitabine (N = 52). Gemcitabine dose was 1000 mg/m2 QW. Primary endpoints for phases 1b and 2, respectively, were phase 2 dose and overall survival V体育安卓版. Secondary objectives included tolerability and biomarkers. .

Results: Dose-escalation suggested a 300-mg/day dose. Primary objective was met: median survival times were 8. 9 and 7. 1 months for galunisertib and placebo, respectively (hazard ratio [HR] = 0. 79 [95% credible interval: 0. 59-1 V体育ios版. 09] and posterior probability HR < 1 = 0. 93). Lower baseline biomarkers macrophage inflammatory protein-1-alpha and interferon-gamma-induced protein 10 were associated with galunisertib benefit. .

Conclusions: Galunisertib-gemcitabine combination improved overall survival vs. gemcitabine in patients with unresectable pancreatic cancer, with minimal added toxicity. Future exploration of galunisertib in pancreatic cancer is ongoing in combination with durvalumab VSports最新版本. .

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Conflict of interest statement

D. M. reports research funding from Shire, Incyte, and Celgene; a consulting role with Eli Lilly, Shire, Baxter and Incyte. G. D. reports research funding from Bavarian Nordici, Genentech, Janssen-Cilag, Roche, Sanofi, Eli Lilly, Exelixis, Sotio and Merck Serono; and travel fees from Roche, Amgen and Sanofi. M. F. reports a consulting role with Eli Lilly. J. T. reports a consulting role with Eli Lilly; speakers’ bureau from Bayer, Amgen and Merck Serono; and travel fees from Bayer. M. K. reports honorarium from Eli Lilly, Genentech, and Roche; a consulting role with Eli Lilly, Genentech, and Roche; and speakers’ bureau from Eli Lilly during the conduct of the study, Genentech, and Roche. A. C. , C. S. , S. T. E. , I. G. and K. A. B. are all current employees and stockholders of Eli Lilly; M. M. F. L. is a former employee and stockholder of Eli Lilly and current employee of Incyte. A. B. is a current employee and stockholder of Advaxis, Inc V体育平台登录. J. T. reports a consulting role with Eli Lilly, Amgen, Boehringer Ingelheim, Celgene, Chugai, Imclone, Merck, Merck Serono, Millenium, Novartis, Roche, Sanofi, Symphogen and Taiho. R. G. -C. , T. M. , D. P. and H. O. declare no competing interests.

Figures

Fig. 1
Fig. 1
Kaplan–Meier estimates of survival by Bayesian vs. frequentist analysis, with 95% Hall–Wellner confidence bands and numbers at risk. overall survival by a Bayesian analysis, b frequentist analysis and c progression-free survival by frequentist analysis. Data for one patient was missing from the progression-free survival analysis. CI=confidence interval; GAL=galunisertib; GEM=gemcitabine; No.=number; PLC=placebo
Fig. 2
Fig. 2
Kaplan–Meier estimates of survival by potential predictive factor, with 95% Hall–Wellner confidence bands and numbers at risk. Overall survival by plasma level of a follicle-stimulating hormone, b interferon-gamma induced protein 10, c macrophage inflammatory protein-1 alpha, and d plasminogen activator inhibitor 1. CL=confidence limits; GAL=galunisertib; GEM=gemcitabine; No.=number; PLC=placebo
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References

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