Phase I-II Study of Intratumoral Urelumab Combined With Nivolumab in Patients With Solid Tumors

Summary

Open label, phase I-II study to evaluate the safety and activity of intratumoral urelumab combined with systemic nivolumab in patients with advanced solid tumors. Serial tumor and blood samples will be obtained during the study to characterize the changes induced by treatment in the tumor microenvironment, as well as predictive biomarkers of response.

Timeline

Start

2019-01-30

Primary completion

2023-01-30

Completion

2023-01-30

Publications

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• Background Van De Voort TJ, Felder MA, Yang RK, Sondel PM, Rakhmilevich AL. Intratumoral delivery of low doses of anti-CD40 mAb combined with monophosphoryl lipid a induces local and systemic antitumor effects in immunocompetent and T cell-deficient mice. J Immunother. 2013 Jan;36(1):29-40. doi: 10.1097/CJI.0b013e3182780f61.
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• Background Tormo D, Checinska A, Alonso-Curbelo D, Perez-Guijarro E, Canon E, Riveiro-Falkenbach E, Calvo TG, Larribere L, Megias D, Mulero F, Piris MA, Dash R, Barral PM, Rodriguez-Peralto JL, Ortiz-Romero P, Tuting T, Fisher PB, Soengas MS. Targeted activation of innate immunity for therapeutic induction of autophagy and apoptosis in melanoma cells. Cancer Cell. 2009 Aug 4;16(2):103-14. doi: 10.1016/j.ccr.2009.07.004.
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• Background Barajas M, Mazzolini G, Genove G, Bilbao R, Narvaiza I, Schmitz V, Sangro B, Melero I, Qian C, Prieto J. Gene therapy of orthotopic hepatocellular carcinoma in rats using adenovirus coding for interleukin 12. Hepatology. 2001 Jan;33(1):52-61. doi: 10.1053/jhep.2001.20796.
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• Background Narvaiza I, Mazzolini G, Barajas M, Duarte M, Zaratiegui M, Qian C, Melero I, Prieto J. Intratumoral coinjection of two adenoviruses, one encoding the chemokine IFN-gamma-inducible protein-10 and another encoding IL-12, results in marked antitumoral synergy. J Immunol. 2000 Mar 15;164(6):3112-22. doi: 10.4049/jimmunol.164.6.3112.
• Background Park BH, Hwang T, Liu TC, Sze DY, Kim JS, Kwon HC, Oh SY, Han SY, Yoon JH, Hong SH, Moon A, Speth K, Park C, Ahn YJ, Daneshmand M, Rhee BG, Pinedo HM, Bell JC, Kirn DH. Use of a targeted oncolytic poxvirus, JX-594, in patients with refractory primary or metastatic liver cancer: a phase I trial. Lancet Oncol. 2008 Jun;9(6):533-42. doi: 10.1016/S1470-2045(08)70107-4. Epub 2008 May 19.
• Background Quetglas JI, Labiano S, Aznar MA, Bolanos E, Azpilikueta A, Rodriguez I, Casales E, Sanchez-Paulete AR, Segura V, Smerdou C, Melero I. Virotherapy with a Semliki Forest Virus-Based Vector Encoding IL12 Synergizes with PD-1/PD-L1 Blockade. Cancer Immunol Res. 2015 May;3(5):449-54. doi: 10.1158/2326-6066.CIR-14-0216. Epub 2015 Feb 17.
• Background Quetglas JI, Dubrot J, Bezunartea J, Sanmamed MF, Hervas-Stubbs S, Smerdou C, Melero I. Immunotherapeutic synergy between anti-CD137 mAb and intratumoral administration of a cytopathic Semliki Forest virus encoding IL-12. Mol Ther. 2012 Sep;20(9):1664-1675. doi: 10.1038/mt.2012.56. Epub 2012 Jun 26.
• Background John LB, Howland LJ, Flynn JK, West AC, Devaud C, Duong CP, Stewart TJ, Westwood JA, Guo ZS, Bartlett DL, Smyth MJ, Kershaw MH, Darcy PK. Oncolytic virus and anti-4-1BB combination therapy elicits strong antitumor immunity against established cancer. Cancer Res. 2012 Apr 1;72(7):1651-60. doi: 10.1158/0008-5472.CAN-11-2788. Epub 2012 Feb 7.
• Background Puzanov I, Milhem MM, Minor D, Hamid O, Li A, Chen L, Chastain M, Gorski KS, Anderson A, Chou J, Kaufman HL, Andtbacka RH. Talimogene Laherparepvec in Combination With Ipilimumab in Previously Untreated, Unresectable Stage IIIB-IV Melanoma. J Clin Oncol. 2016 Aug 1;34(22):2619-26. doi: 10.1200/JCO.2016.67.1529. Epub 2016 Jun 13.
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• Background Cripe TP, Ngo MC, Geller JI, Louis CU, Currier MA, Racadio JM, Towbin AJ, Rooney CM, Pelusio A, Moon A, Hwang TH, Burke JM, Bell JC, Kirn DH, Breitbach CJ. Phase 1 study of intratumoral Pexa-Vec (JX-594), an oncolytic and immunotherapeutic vaccinia virus, in pediatric cancer patients. Mol Ther. 2015 Mar;23(3):602-8. doi: 10.1038/mt.2014.243. Epub 2014 Dec 22.
• Background Huang PI, Chang JF, Kirn DH, Liu TC. Targeted genetic and viral therapy for advanced head and neck cancers. Drug Discov Today. 2009 Jun;14(11-12):570-8. doi: 10.1016/j.drudis.2009.03.008. Epub 2009 Mar 17.
• Background Liu TC, Thorne SH, Kirn DH. Oncolytic adenoviruses for cancer gene therapy. Methods Mol Biol. 2008;433:243-58. doi: 10.1007/978-1-59745-237-3_15.
• Background Huarte E, Larrea E, Hernandez-Alcoceba R, Alfaro C, Murillo O, Arina A, Tirapu I, Azpilicueta A, Hervas-Stubbs S, Bortolanza S, Perez-Gracia JL, Civeira MP, Prieto J, Riezu-Boj JI, Melero I. Recombinant adenoviral vectors turn on the type I interferon system without inhibition of transgene expression and viral replication. Mol Ther. 2006 Jul;14(1):129-38. doi: 10.1016/j.ymthe.2006.02.015. Epub 2006 Apr 19.
• Background Kawai T, Akira S. Toll-like receptors and their crosstalk with other innate receptors in infection and immunity. Immunity. 2011 May 27;34(5):637-50. doi: 10.1016/j.immuni.2011.05.006.
• Background Takeuchi O, Akira S. MDA5/RIG-I and virus recognition. Curr Opin Immunol. 2008 Feb;20(1):17-22. doi: 10.1016/j.coi.2008.01.002. Epub 2008 Feb 12.
• Background Sharma P, Allison JP. The future of immune checkpoint therapy. Science. 2015 Apr 3;348(6230):56-61. doi: 10.1126/science.aaa8172.
• Background Topalian SL, Drake CG, Pardoll DM. Immune checkpoint blockade: a common denominator approach to cancer therapy. Cancer Cell. 2015 Apr 13;27(4):450-61. doi: 10.1016/j.ccell.2015.03.001. Epub 2015 Apr 6.
• Background Kohrt HE, Tumeh PC, Benson D, Bhardwaj N, Brody J, Formenti S, Fox BA, Galon J, June CH, Kalos M, Kirsch I, Kleen T, Kroemer G, Lanier L, Levy R, Lyerly HK, Maecker H, Marabelle A, Melenhorst J, Miller J, Melero I, Odunsi K, Palucka K, Peoples G, Ribas A, Robins H, Robinson W, Serafini T, Sondel P, Vivier E, Weber J, Wolchok J, Zitvogel L, Disis ML, Cheever MA; Cancer Immunotherapy Trials Network (CITN). Immunodynamics: a cancer immunotherapy trials network review of immune monitoring in immuno-oncology clinical trials. J Immunother Cancer. 2016 Mar 15;4:15. doi: 10.1186/s40425-016-0118-0. eCollection 2016.
• Background Melief CJ. Selective activation of oxygen-deprived tumor-infiltrating lymphocytes through local intratumoral delivery of CD137 monoclonal antibodies. Cancer Discov. 2012 Jul;2(7):586-7. doi: 10.1158/2159-8290.CD-12-0229.
• Background Fransen MF, van der Sluis TC, Ossendorp F, Arens R, Melief CJ. Controlled local delivery of CTLA-4 blocking antibody induces CD8+ T-cell-dependent tumor eradication and decreases risk of toxic side effects. Clin Cancer Res. 2013 Oct 1;19(19):5381-9. doi: 10.1158/1078-0432.CCR-12-0781. Epub 2013 Jun 20.
• Background Fransen MF, Sluijter M, Morreau H, Arens R, Melief CJ. Local activation of CD8 T cells and systemic tumor eradication without toxicity via slow release and local delivery of agonistic CD40 antibody. Clin Cancer Res. 2011 Apr 15;17(8):2270-80. doi: 10.1158/1078-0432.CCR-10-2888. Epub 2011 Mar 9.
• Background Fransen MF, Cordfunke RA, Sluijter M, van Steenbergen MJ, Drijfhout JW, Ossendorp F, Hennink WE, Melief CJ. Effectiveness of slow-release systems in CD40 agonistic antibody immunotherapy of cancer. Vaccine. 2014 Mar 26;32(15):1654-60. doi: 10.1016/j.vaccine.2014.01.056. Epub 2014 Feb 7.
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• Background Marabelle A, Kohrt H, Sagiv-Barfi I, Ajami B, Axtell RC, Zhou G, Rajapaksa R, Green MR, Torchia J, Brody J, Luong R, Rosenblum MD, Steinman L, Levitsky HI, Tse V, Levy R. Depleting tumor-specific Tregs at a single site eradicates disseminated tumors. J Clin Invest. 2013 Jun;123(6):2447-63. doi: 10.1172/JCI64859.
• Background Lehmann S, Perera R, Grimm HP, Sam J, Colombetti S, Fauti T, Fahrni L, Schaller T, Freimoser-Grundschober A, Zielonka J, Stoma S, Rudin M, Klein C, Umana P, Gerdes C, Bacac M. In Vivo Fluorescence Imaging of the Activity of CEA TCB, a Novel T-Cell Bispecific Antibody, Reveals Highly Specific Tumor Targeting and Fast Induction of T-Cell-Mediated Tumor Killing. Clin Cancer Res. 2016 Sep 1;22(17):4417-27. doi: 10.1158/1078-0432.CCR-15-2622. Epub 2016 Apr 26.
• Background Palazon A, Martinez-Forero I, Teijeira A, Morales-Kastresana A, Alfaro C, Sanmamed MF, Perez-Gracia JL, Penuelas I, Hervas-Stubbs S, Rouzaut A, de Landazuri MO, Jure-Kunkel M, Aragones J, Melero I. The HIF-1alpha hypoxia response in tumor-infiltrating T lymphocytes induces functional CD137 (4-1BB) for immunotherapy. Cancer Discov. 2012 Jul;2(7):608-23. doi: 10.1158/2159-8290.CD-11-0314. Epub 2012 Jun 19.
• Background Beatty GL, Torigian DA, Chiorean EG, Saboury B, Brothers A, Alavi A, Troxel AB, Sun W, Teitelbaum UR, Vonderheide RH, O'Dwyer PJ. A phase I study of an agonist CD40 monoclonal antibody (CP-870,893) in combination with gemcitabine in patients with advanced pancreatic ductal adenocarcinoma. Clin Cancer Res. 2013 Nov 15;19(22):6286-95. doi: 10.1158/1078-0432.CCR-13-1320. Epub 2013 Aug 27.
• Background Dubrot J, Milheiro F, Alfaro C, Palazon A, Martinez-Forero I, Perez-Gracia JL, Morales-Kastresana A, Romero-Trevejo JL, Ochoa MC, Hervas-Stubbs S, Prieto J, Jure-Kunkel M, Chen L, Melero I. Treatment with anti-CD137 mAbs causes intense accumulations of liver T cells without selective antitumor immunotherapeutic effects in this organ. Cancer Immunol Immunother. 2010 Aug;59(8):1223-33. doi: 10.1007/s00262-010-0846-9. Epub 2010 Mar 25.
• Background Nowak AK, Cook AM, McDonnell AM, Millward MJ, Creaney J, Francis RJ, Hasani A, Segal A, Musk AW, Turlach BA, McCoy MJ, Robinson BW, Lake RA. A phase 1b clinical trial of the CD40-activating antibody CP-870,893 in combination with cisplatin and pemetrexed in malignant pleural mesothelioma. Ann Oncol. 2015 Dec;26(12):2483-90. doi: 10.1093/annonc/mdv387. Epub 2015 Sep 18.
• Background Vonderheide RH, Flaherty KT, Khalil M, Stumacher MS, Bajor DL, Hutnick NA, Sullivan P, Mahany JJ, Gallagher M, Kramer A, Green SJ, O'Dwyer PJ, Running KL, Huhn RD, Antonia SJ. Clinical activity and immune modulation in cancer patients treated with CP-870,893, a novel CD40 agonist monoclonal antibody. J Clin Oncol. 2007 Mar 1;25(7):876-83. doi: 10.1200/JCO.2006.08.3311.
• Background Bol KF, Schreibelt G, Gerritsen WR, de Vries IJ, Figdor CG. Dendritic Cell-Based Immunotherapy: State of the Art and Beyond. Clin Cancer Res. 2016 Apr 15;22(8):1897-906. doi: 10.1158/1078-0432.CCR-15-1399.
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• Background Bedrosian I, Mick R, Xu S, Nisenbaum H, Faries M, Zhang P, Cohen PA, Koski G, Czerniecki BJ. Intranodal administration of peptide-pulsed mature dendritic cell vaccines results in superior CD8+ T-cell function in melanoma patients. J Clin Oncol. 2003 Oct 15;21(20):3826-35. doi: 10.1200/JCO.2003.04.042.
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• Background Melero I, Duarte M, Ruiz J, Sangro B, Galofre J, Mazzolini G, Bustos M, Qian C, Prieto J. Intratumoral injection of bone-marrow derived dendritic cells engineered to produce interleukin-12 induces complete regression of established murine transplantable colon adenocarcinomas. Gene Ther. 1999 Oct;6(10):1779-84. doi: 10.1038/sj.gt.3301010.
• Background Nishioka Y, Hirao M, Robbins PD, Lotze MT, Tahara H. Induction of systemic and therapeutic antitumor immunity using intratumoral injection of dendritic cells genetically modified to express interleukin 12. Cancer Res. 1999 Aug 15;59(16):4035-41.
• Background Van Lint S, Renmans D, Broos K, Goethals L, Maenhout S, Benteyn D, Goyvaerts C, Du Four S, Van der Jeught K, Bialkowski L, Flamand V, Heirman C, Thielemans K, Breckpot K. Intratumoral Delivery of TriMix mRNA Results in T-cell Activation by Cross-Presenting Dendritic Cells. Cancer Immunol Res. 2016 Feb;4(2):146-56. doi: 10.1158/2326-6066.CIR-15-0163. Epub 2015 Dec 11.
• Background Mazzolini G, Alfaro C, Sangro B, Feijoo E, Ruiz J, Benito A, Tirapu I, Arina A, Sola J, Herraiz M, Lucena F, Olague C, Subtil J, Quiroga J, Herrero I, Sadaba B, Bendandi M, Qian C, Prieto J, Melero I. Intratumoral injection of dendritic cells engineered to secrete interleukin-12 by recombinant adenovirus in patients with metastatic gastrointestinal carcinomas. J Clin Oncol. 2005 Feb 10;23(5):999-1010. doi: 10.1200/JCO.2005.00.463. Epub 2004 Dec 14.
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• Background Melero I, Arina A, Murillo O, Dubrot J, Alfaro C, Perez-Gracia JL, Bendandi M, Hervas-Stubbs S. Immunogenic cell death and cross-priming are reaching the clinical immunotherapy arena. Clin Cancer Res. 2006 Apr 15;12(8):2385-9. doi: 10.1158/1078-0432.CCR-06-0314. No abstract available.
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• Background Chi KH, Liu SJ, Li CP, Kuo HP, Wang YS, Chao Y, Hsieh SL. Combination of conformal radiotherapy and intratumoral injection of adoptive dendritic cell immunotherapy in refractory hepatoma. J Immunother. 2005 Mar-Apr;28(2):129-35. doi: 10.1097/01.cji.0000154248.74383.5e.
• Background Breton G, Lee J, Zhou YJ, Schreiber JJ, Keler T, Puhr S, Anandasabapathy N, Schlesinger S, Caskey M, Liu K, Nussenzweig MC. Circulating precursors of human CD1c+ and CD141+ dendritic cells. J Exp Med. 2015 Mar 9;212(3):401-13. doi: 10.1084/jem.20141441. Epub 2015 Feb 16.
• Background Gorelik L, Flavell RA. Transforming growth factor-beta in T-cell biology. Nat Rev Immunol. 2002 Jan;2(1):46-53. doi: 10.1038/nri704.
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• Background Maus MV, June CH. Making Better Chimeric Antigen Receptors for Adoptive T-cell Therapy. Clin Cancer Res. 2016 Apr 15;22(8):1875-84. doi: 10.1158/1078-0432.CCR-15-1433.
• Background Rosenberg SA, Restifo NP. Adoptive cell transfer as personalized immunotherapy for human cancer. Science. 2015 Apr 3;348(6230):62-8. doi: 10.1126/science.aaa4967.
• Background Melero I, Rouzaut A, Motz GT, Coukos G. T-cell and NK-cell infiltration into solid tumors: a key limiting factor for efficacious cancer immunotherapy. Cancer Discov. 2014 May;4(5):522-6. doi: 10.1158/2159-8290.CD-13-0985.
• Background Arina A, Murillo O, Hervas-Stubbs S, Azpilikueta A, Dubrot J, Tirapu I, Huarte E, Alfaro C, Perez-Gracia JL, Gonzalez-Aseguinolaza G, Sarobe P, Lasarte JJ, Jamieson A, Prieto J, Raulet DH, Melero I. The combined actions of NK and T lymphocytes are necessary to reject an EGFP+ mesenchymal tumor through mechanisms dependent on NKG2D and IFN gamma. Int J Cancer. 2007 Sep 15;121(6):1282-95. doi: 10.1002/ijc.22795.
• Background Golden EB, Pellicciotta I, Demaria S, Barcellos-Hoff MH, Formenti SC. The convergence of radiation and immunogenic cell death signaling pathways. Front Oncol. 2012 Aug 7;2:88. doi: 10.3389/fonc.2012.00088. eCollection 2012.
• Background Kepp, O., L. Senovilla, I. Vitale, E. Vacchelli, S. Adjemian, P. Agostinis, L. Apetoh, F. Aranda, V. Barnaba, N. Bloy, L. Bracci, K. Breckpot, D. Brough, A. Buque, M. G. Castro, M. Cirone, M. I. Colombo, I. Cremer, S. Demaria, L. Dini, A. G. Eliopoulos, A. Faggioni, S. C. Formenti, J. Fucikova, L. Gabriele, U. S. Gaipl, J. Galon, A. Garg, F. Ghiringhelli, N. A. Giese, Z. S. Guo, A. Hemminki, M. Herrmann, J. W. Hodge, S. Holdenrieder, J. Honeychurch, H. M. Hu, X. Huang, T. M. Illidge, K. Kono, M. Korbelik, D. V. Krysko, S. Loi, P. R. Lowenstein, E. Lugli, Y. Ma, F. Madeo, A. A. Manfredi, I. Martins, D. Mavilio, L. Menger, N. Merendino, M. Michaud, G. Mignot, K. L. Mossman, G. Multhoff, R. Oehler, F. Palombo, T. Panaretakis, J. Pol, E. Proietti, J. E. Ricci, C. Riganti, P. Rovere-Querini, A. Rubartelli, A. Sistigu, M. J. Smyth, J. Sonnemann, R. Spisek, J. Stagg, A. Q. Sukkurwala, E. Tartour, A. Thorburn, S. H. Thorne, P. Vandenabeele, F. Velotti, S. T. Workenhe, H. Yang, W. X. Zong, L. Zitvogel, G. Kroemer, and L. Galluzzi. 2014. Consensus guidelines for the detection of immunogenic cell death. Oncoimmunology 3: e955691
• Background Antoniades J, Brady LW, Lightfoot DA. Lymphangiographic demonstration of the abscopal effect in patients with malignant lymphomas. Int J Radiat Oncol Biol Phys. 1977 Jan-Feb;2(1-2):141-7. doi: 10.1016/0360-3016(77)90020-7. No abstract available.
• Background Deng L, Liang H, Burnette B, Beckett M, Darga T, Weichselbaum RR, Fu YX. Irradiation and anti-PD-L1 treatment synergistically promote antitumor immunity in mice. J Clin Invest. 2014 Feb;124(2):687-95. doi: 10.1172/JCI67313. Epub 2014 Jan 2.
• Background Ruocco MG, Pilones KA, Kawashima N, Cammer M, Huang J, Babb JS, Liu M, Formenti SC, Dustin ML, Demaria S. Suppressing T cell motility induced by anti-CTLA-4 monotherapy improves antitumor effects. J Clin Invest. 2012 Oct;122(10):3718-30. doi: 10.1172/JCI61931. Epub 2012 Sep 4.
• Background Twyman-Saint Victor C, Rech AJ, Maity A, Rengan R, Pauken KE, Stelekati E, Benci JL, Xu B, Dada H, Odorizzi PM, Herati RS, Mansfield KD, Patsch D, Amaravadi RK, Schuchter LM, Ishwaran H, Mick R, Pryma DA, Xu X, Feldman MD, Gangadhar TC, Hahn SM, Wherry EJ, Vonderheide RH, Minn AJ. Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer. Nature. 2015 Apr 16;520(7547):373-7. doi: 10.1038/nature14292. Epub 2015 Mar 9.
• Background Postow MA, Callahan MK, Barker CA, Yamada Y, Yuan J, Kitano S, Mu Z, Rasalan T, Adamow M, Ritter E, Sedrak C, Jungbluth AA, Chua R, Yang AS, Roman RA, Rosner S, Benson B, Allison JP, Lesokhin AM, Gnjatic S, Wolchok JD. Immunologic correlates of the abscopal effect in a patient with melanoma. N Engl J Med. 2012 Mar 8;366(10):925-31. doi: 10.1056/NEJMoa1112824.
• Background Shi L, Chen L, Wu C, Zhu Y, Xu B, Zheng X, Sun M, Wen W, Dai X, Yang M, Lv Q, Lu B, Jiang J. PD-1 Blockade Boosts Radiofrequency Ablation-Elicited Adaptive Immune Responses against Tumor. Clin Cancer Res. 2016 Mar 1;22(5):1173-1184. doi: 10.1158/1078-0432.CCR-15-1352.
• Background Mozzillo N, Simeone E, Benedetto L, Curvietto M, Giannarelli D, Gentilcore G, Camerlingo R, Capone M, Madonna G, Festino L, Caraco C, Di Monta G, Marone U, Di Marzo M, Grimaldi AM, Mori S, Ciliberto G, Ascierto PA. Assessing a novel immuno-oncology-based combination therapy: Ipilimumab plus electrochemotherapy. Oncoimmunology. 2015 May 22;4(6):e1008842. doi: 10.1080/2162402X.2015.1008842. eCollection 2015 Jun.
• Background Korangy, F., M. ElGindi, D. Pratt, D. Venzon, A. Duffy, O. Makarova-Rusher, S. Kerkar, D. Kleiner, B. Wood, and T. Greten. 2016. Tremelimimab activates CD4 and CD8+T cells in patients with hepatocellular carcinoma. Cancer immunology research 4
• Background Barker HE, Paget JT, Khan AA, Harrington KJ. The tumour microenvironment after radiotherapy: mechanisms of resistance and recurrence. Nat Rev Cancer. 2015 Jul;15(7):409-25. doi: 10.1038/nrc3958.
• Background Sandoval F, Terme M, Nizard M, Badoual C, Bureau MF, Freyburger L, Clement O, Marcheteau E, Gey A, Fraisse G, Bouguin C, Merillon N, Dransart E, Tran T, Quintin-Colonna F, Autret G, Thiebaud M, Suleman M, Riffault S, Wu TC, Launay O, Danel C, Taieb J, Richardson J, Zitvogel L, Fridman WH, Johannes L, Tartour E. Mucosal imprinting of vaccine-induced CD8(+) T cells is crucial to inhibit the growth of mucosal tumors. Sci Transl Med. 2013 Feb 13;5(172):172ra20. doi: 10.1126/scitranslmed.3004888.
• Background Mikhak Z, Strassner JP, Luster AD. Lung dendritic cells imprint T cell lung homing and promote lung immunity through the chemokine receptor CCR4. J Exp Med. 2013 Aug 26;210(9):1855-69. doi: 10.1084/jem.20130091. Epub 2013 Aug 19.
• Background Kaufman HL, Amatruda T, Reid T, Gonzalez R, Glaspy J, Whitman E, Harrington K, Nemunaitis J, Zloza A, Wolf M, Senzer NN. Systemic versus local responses in melanoma patients treated with talimogene laherparepvec from a multi-institutional phase II study. J Immunother Cancer. 2016 Mar 15;4:12. doi: 10.1186/s40425-016-0116-2. eCollection 2016.
• Background Melero I, Berman DM, Aznar MA, Korman AJ, Perez Gracia JL, Haanen J. Evolving synergistic combinations of targeted immunotherapies to combat cancer. Nat Rev Cancer. 2015 Aug;15(8):457-72. doi: 10.1038/nrc3973.
• Background Whiteside TL, Demaria S, Rodriguez-Ruiz ME, Zarour HM, Melero I. Emerging Opportunities and Challenges in Cancer Immunotherapy. Clin Cancer Res. 2016 Apr 15;22(8):1845-55. doi: 10.1158/1078-0432.CCR-16-0049.
• Background Berraondo P, Ochoa MC, Rodriguez-Ruiz ME, Minute L, Lasarte JJ, Melero I. Immunostimulatory Monoclonal Antibodies and Immunomodulation: Harvesting the Crop. Cancer Res. 2016 May 15;76(10):2863-7. doi: 10.1158/0008-5472.CAN-15-3279. Epub 2016 May 2.
• Sanmamed MF, de Andrea CE, Ruiz-Guillamon D, Rodriguez-Ruiz ME, Ortego I, Eguren-Santamaria I, Benito A, Lopez-Janeiro A, Gonzalez Gomariz J, Villalba-Esparza M, Molina A, Krasko A, Ponz-Sarvise M, Lopez-Picazo JM, Gomis G, Molero-Glez P, Alexandru R, Perez-Dominguez P, Rodriguez I, Sanchez-Gregorio S, Perez-Gracia JL, Melero I. Safety, Feasibility, and Pharmacodynamic Activity of Intratumoral Injections of the Agonist Anti-CD137 (4-1BB) mAb Urelumab in Combination with Nivolumab. Clin Cancer Res. 2026 Mar 16;32(6):1036-1045. doi: 10.1158/1078-0432.CCR-25-2502.

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Indications