Lag-3 and Gemcitabine for Treatment of Advanced Pancreas Cancer

Summary

The overall purpose of this research is to evaluate the safety and toxicity of an investigational medication, IMP321, in patients being treated with gemcitabine. IMP321 is a synthetic protein (made in the laboratory to simulate a protein that your body makes on its own) and was designed to stimulate the immune system with the overall objective of improving the body's capacity to react to your pancreas cancer.

Timeline

Start

2009-02

Primary completion

2010-02

Completion

2012-09

Publications

• Background Storniolo AM, Allerheiligen SR, Pearce HL. Preclinical, pharmacologic, and phase I studies of gemcitabine. Semin Oncol. 1997 Apr;24(2 Suppl 7):S7-2-S7-7.
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• Background Buisson S, Triebel F. MHC class II engagement by its ligand LAG-3 (CD223) leads to a distinct pattern of chemokine and chemokine receptor expression by human dendritic cells. Vaccine. 2003 Feb 14;21(9-10):862-8. doi: 10.1016/s0264-410x(02)00533-9.
• Background Andreae S, Buisson S, Triebel F. MHC class II signal transduction in human dendritic cells induced by a natural ligand, the LAG-3 protein (CD223). Blood. 2003 Sep 15;102(6):2130-7. doi: 10.1182/blood-2003-01-0273. Epub 2003 May 29.
• Background El Mir S, Triebel F. A soluble lymphocyte activation gene-3 molecule used as a vaccine adjuvant elicits greater humoral and cellular immune responses to both particulate and soluble antigens. J Immunol. 2000 Jun 1;164(11):5583-9. doi: 10.4049/jimmunol.164.11.5583.
• Background Prigent P, El Mir S, Dreano M, Triebel F. Lymphocyte activation gene-3 induces tumor regression and antitumor immune responses. Eur J Immunol. 1999 Dec;29(12):3867-76. doi: 10.1002/(SICI)1521-4141(199912)29:123.0.CO;2-E.
• Background Cappello P, Triebel F, Iezzi M, Caorsi C, Quaglino E, Lollini PL, Amici A, Di Carlo E, Musiani P, Giovarelli M, Forni G. LAG-3 enables DNA vaccination to persistently prevent mammary carcinogenesis in HER-2/neu transgenic BALB/c mice. Cancer Res. 2003 May 15;63(10):2518-25.
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• Background Hannier S, Tournier M, Bismuth G, Triebel F. CD3/TCR complex-associated lymphocyte activation gene-3 molecules inhibit CD3/TCR signaling. J Immunol. 1998 Oct 15;161(8):4058-65.
• Background Workman CJ, Vignali DA. The CD4-related molecule, LAG-3 (CD223), regulates the expansion of activated T cells. Eur J Immunol. 2003 Apr;33(4):970-9. doi: 10.1002/eji.200323382.
• Background Macon-Lemaitre L, Triebel F. The negative regulatory function of the lymphocyte-activation gene-3 co-receptor (CD223) on human T cells. Immunology. 2005 Jun;115(2):170-8. doi: 10.1111/j.1365-2567.2005.02145.x.
• Background Huang CT, Workman CJ, Flies D, Pan X, Marson AL, Zhou G, Hipkiss EL, Ravi S, Kowalski J, Levitsky HI, Powell JD, Pardoll DM, Drake CG, Vignali DA. Role of LAG-3 in regulatory T cells. Immunity. 2004 Oct;21(4):503-13. doi: 10.1016/j.immuni.2004.08.010.
• Background Workman CJ, Vignali DA. Negative regulation of T cell homeostasis by lymphocyte activation gene-3 (CD223). J Immunol. 2005 Jan 15;174(2):688-95. doi: 10.4049/jimmunol.174.2.688.
• Background Triebel F, Hacene K, Pichon MF. A soluble lymphocyte activation gene-3 (sLAG-3) protein as a prognostic factor in human breast cancer expressing estrogen or progesterone receptors. Cancer Lett. 2006 Apr 8;235(1):147-53. doi: 10.1016/j.canlet.2005.04.015. Epub 2005 Jun 8.
• Background Lienhardt C, Azzurri A, Amedei A, Fielding K, Sillah J, Sow OY, Bah B, Benagiano M, Diallo A, Manetti R, Manneh K, Gustafson P, Bennett S, D'Elios MM, McAdam K, Del Prete G. Active tuberculosis in Africa is associated with reduced Th1 and increased Th2 activity in vivo. Eur J Immunol. 2002 Jun;32(6):1605-13. doi: 10.1002/1521-4141(200206)32:63.0.CO;2-6.
• Background Immutep. 2006. ImmuFact IMP321 Product Information Brochure.
• Background Fougeray S, Brignone C, Triebel F. A soluble LAG-3 protein as an immunopotentiator for therapeutic vaccines: Preclinical evaluation of IMP321. Vaccine. 2006 Jun 29;24(26):5426-33. doi: 10.1016/j.vaccine.2006.03.050. Epub 2006 Mar 31.
• Background Tseng JF, Willett CG, Fernandez-del Castillo C, Ryan DP, Clark JW, Zhu AX, Rattner DW, Winkelmann JL, Warshaw AL. Patients undergoing treatment for pancreatic adenocarcinoma can mount an effective immune response to vaccinations. Pancreatology. 2005;5(1):67-74. doi: 10.1159/000084492. Epub 2005 Mar 15.
• Background Co, E.L.a., Gemcitabine Product Info. 2003.
• Background Series, M.H., 2003. MICROMEDEX, Greenwood Village, Colorado
• Background Hawkins WG, Gold JS, Dyall R, Wolchok JD, Hoos A, Bowne WB, Srinivasan R, Houghton AN, Lewis JJ. Immunization with DNA coding for gp100 results in CD4 T-cell independent antitumor immunity. Surgery. 2000 Aug;128(2):273-80. doi: 10.1067/msy.2000.107421.
• Background Ko K, Yamazaki S, Nakamura K, Nishioka T, Hirota K, Yamaguchi T, Shimizu J, Nomura T, Chiba T, Sakaguchi S. Treatment of advanced tumors with agonistic anti-GITR mAb and its effects on tumor-infiltrating Foxp3+CD25+CD4+ regulatory T cells. J Exp Med. 2005 Oct 3;202(7):885-91. doi: 10.1084/jem.20050940. Epub 2005 Sep 26.
• Background Moore MJ, Goldstein D, Hamm J, Figer A, Hecht JR, Gallinger S, Au HJ, Murawa P, Walde D, Wolff RA, Campos D, Lim R, Ding K, Clark G, Voskoglou-Nomikos T, Ptasynski M, Parulekar W; National Cancer Institute of Canada Clinical Trials Group. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group. J Clin Oncol. 2007 May 20;25(15):1960-6. doi: 10.1200/JCO.2006.07.9525. Epub 2007 Apr 23.

Drugs

Indications