@article{9d911378e5214bfeb2144ac1e451264d,
title = "A Phase II Study of Allogeneic GM-CSF–Transfected Pancreatic Tumor Vaccine (GVAX) with Ipilimumab as Maintenance Treatment for Metastatic Pancreatic Cancer",
abstract = "Purpose: This phase II study tested granulocyte-macrophage colony-stimulating factor (GM-CSF)-allogeneic pancreatic tumor cells (GVAX) and ipilimumab in metastatic pancreatic ductal adenocarcinoma (PDA) in the maintenance setting. Patients and Methods: Patients with PDA who were treated with front-line chemotherapy consisting of 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) in the metastatic setting and had ongoing response or stable disease after 8–12 doses were eligible. Patients were randomized 1:1 to treatment with GVAX and ipilimumab given every 3 weeks for four doses then every 8 weeks (Arm A) or to FOLFIRINOX continuation (Arm B). The primary objective was to compare overall survival (OS) between the two arms. Results: Eighty-two patients were included in the final analysis (Arm A: 40; Arm B: 42). The study was stopped for futility after interim analysis. Median OS was 9.38 months [95% confidence interval (CI), 5.0–12.2] for Arm A and 14.7 months (95% CI, 11.6–20.0) for Arm B (HR, 1.75; P = 0.019). Using immune-related response criteria, two partial responses (5.7%) were observed in Arm A and four (13.8%) in Arm B. GVAX {\th} ipilimumab promoted T-cell differentiation into effector memory phenotypes both in the periphery and in the tumor microenvironment and increased M1 macrophages in the tumor. Conclusions: GVAX and ipilimumab maintenance therapy did not improve OS over continuation of chemotherapy and resulted in a numerically inferior survival in metastatic PDA. However, clinical responses and biological effects on immune cells were observed. Further study of novel combinations in the maintenance treatment of metastatic PDA is feasible.",
author = "Wu, {Annie A.} and Bever, {Katherine M.} and Ho, {Won Jin} and Fertig, {Elana J.} and Nan Niu and Lei Zheng and Parkinson, {Rose M.} and Durham, {Jennifer N.} and Beth Onners and Ferguson, {Anna K.} and Cara Wilt and Ko, {Andrew H.} and Andrea Wang-Gillam and Laheru, {Daniel A.} and Anders, {Robert A.} and Thompson, {Elizabeth D.} and Sugar, {Elizabeth A.} and Jaffee, {Elizabeth M.} and Le, {Dung T.}",
note = "Funding Information: W.J. Ho reports other from Rodeo Therapeutics (royalties) outside the submitted work. E.J. Fertig reports personal fees from Champions Oncology outside the submitted work. L. Zheng reports other from Aduro (Licensign GVAX); grants from BMS, Merck, Amgen, iTeos, Inxmed, and Halozyme; grants and personal fees from NovaRock; personal fees from Biosion, Akrevia, Datarevive, QED, Xilio, and Natera; personal fees and other from Alphamab (stock); and personal fees and other from Mingruizhiyao (share) during the conduct of the study. A.H. Ko reports grants from Celgene (paid directly to institution), Roche/Genentech (paid directly to institution), Halozyme (paid directly to institution), Merrimack (paid directly to institution), Merck (paid directly to institution), BMS (paid directly to institution), Abgenomics (paid directly to institution), and personal fees from Erytech (data monitoring committee) outside the submitted work. A. Wang-Gillam reports personal fees from Ipsen (consultant), Jacobio (consultant), Merrimack (consultant), Tyme (consultant), BMS (consultant), AstraZeneca (consultant), Merck (consultant), Eisai (consultant), and Bayer (consultant) outside the submitted work. R.A. Anders reports grants and personal fees from Bristol Myers Squibb and FLX Bio; personal fees from Merk SD and AstraZeneca; and grants from SU2C and NIH during the conduct of the study. E.A. Sugar reports grants from NCI (salary support from NCI grants) during the conduct of the study. E.M. Jaffee reports a patent for GVAX/mesothelin issued, licensed, and with royalties paid from Aduro Biotech. D.T. Le reports grants and personal fees from BMS and grants from Aduro Biotech during the conduct of the study; grants and Funding Information: D.T. Le and E.M. Jaffee were funded by FDA/R01 (1RO1FD004819), NCI/NIH Spore in Gastrointestinal Cancer (P50CA062924 and CA62924), and the Viragh Family Foundation's Pancreatic Cancer Fund. E.M. Jaffee was also funded by the Broccoli Foundation and the Emerson Collective Cancer Research Fund. Publisher Copyright: {\textcopyright} 2020 American Association for Cancer Research.",
year = "2020",
month = oct,
day = "1",
doi = "10.1158/1078-0432.CCR-20-1025",
language = "English",
volume = "26",
pages = "5129--5139",
journal = "Clinical Cancer Research",
issn = "1078-0432",
number = "19",
}