Maintenance treatment with the immunomodulator MGN1703, a Toll-like receptor 9 (TLR9) agonist, in patients with metastatic colorectal carcinoma and disease control after chemotherapy: A randomised, double-blind, placebo-controlled trial

Journal of Cancer Research and Clinical Oncology

Volumn 140, Issue 9, 2014, Pages 1615-1624

  Schmoll, Hans Joachim ^a   Wittig, Burghardt ^b   Arnold, Dirk ^c   Riera Knorrenschild, Jorge ^d   Nitsche, Dieter ^e   Kroening, Hendrik ^e   Mayer, Frank ^f   Andel, Johannes ^e   Ziebermayr, Reinhard ^e   Scheithauer, Werner ^g  

^a MARTIN LUTHER UNIVERSITÄT HALLE WITTENBERG   (Germany)

^b FREIE UNIVERSITÄT BERLIN   (Germany)

^c UNIVERSITY OF FREIBURG   (Germany)

^d UNIVERSITY HOSPITAL MARBURG   (Germany)

^e Hematology Oncology Gastroenterology Barmherziger Schwestern Linz ^*  (Austria)

^f UNIVERSITY HOSPITAL TÜBINGEN   (Germany)

^g MEDICAL UNIVERSITY OF VIENNA   (Austria)

Author keywords

Colorectal cancer; Immunomodulator; Maintenance; MGN1703; TLR9 agonist

Indexed keywords

ASPARTATE AMINOTRANSFERASE; BEVACIZUMAB; CAPECITABINE; CAPECITABINE PLUS OXALIPLATIN; CARCINOEMBRYONIC ANTIGEN; FLUOROPYRIMIDINE; FLUOROURACIL; FOLINIC ACID; IMMUNOMODULATING AGENT; IRINOTECAN; MGN 1703; OXALIPLATIN; PLACEBO; TOLL LIKE RECEPTOR AGONIST; UNCLASSIFIED DRUG;

ADULT; ARTICLE; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; CANCER CHEMOTHERAPY; CANCER CONTROL; CANCER IMMUNOTHERAPY; CANCER PATIENT; COLORECTAL CARCINOMA; CONTROLLED STUDY; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG ERUPTION; DRUG SAFETY; DRUG WITHDRAWAL; FATIGUE; FEMALE; FLU LIKE SYNDROME; FOLLOW UP; HUMAN; HYPERTENSION; ILEUS; IMMUNE SYSTEM; INDUCTION CHEMOTHERAPY; INJECTION SITE REACTION; MAINTENANCE CHEMOTHERAPY; MAJOR CLINICAL STUDY; MALE; METASTATIC COLORECTAL CANCER; METASTATIC COLORECTAL CARCINOMA; NATURAL KILLER T CELL; NEUTROPENIA; OVERALL SURVIVAL; PAIN; PARESTHESIA; PHASE 2 CLINICAL TRIAL; POLYNEUROPATHY; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; PROSPECTIVE STUDY; PRURITUS; RANDOMIZED CONTROLLED TRIAL; RETROSPECTIVE STUDY; SENSORY POLYNEUROPATHY; SEPSIS; SIDE EFFECT; TUMOR VOLUME; VIRUS PNEUMONIA;

ADULT; AGED; AGED, 80 AND OVER; COLORECTAL NEOPLASMS; DISEASE-FREE SURVIVAL; DOUBLE-BLIND METHOD; FEMALE; HUMANS; IMMUNOLOGIC FACTORS; MALE; MIDDLE AGED; RETROSPECTIVE STUDIES; TOLL-LIKE RECEPTOR 9;

EID: 84902676837     PISSN: 01715216     EISSN: 14321335     Source Type: Journal    
DOI: 10.1007/s00432-014-1682-7     Document Type: Article

References (33)

1. Ahmad-Nejad P, Häcker H, Rutz M, Bauer S, Vabulas RM, Wagner H (2002) Bacterial CpG-DNA and lipopolysaccharides activate Toll-like receptors at distinct cellular compartments. Eur J Immunol 32:1958-1968 (Pubitemid 34814552)
2. Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, Drake CG, Camacho LH, Kauh J, Odunsi K, Pitot HC, Hamid O, Bhatia S, Martins R, Eaton K, Chen S, Salay TM, Alaparthy S, Grosso JF, Korman AJ, Parker SM, Agrawal S, Goldberg SM, Pardoll DM, Gupta A, Wigginton JM (2012) Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med 366:2455-2465
3. Carpentier A, Laigle-Donadey F, Zohar S, Capelle L, Behin A, Tibi A, Martin-Duverneuil N, Sanson M, Lacomblez L, Taillibert S, Puybasset L, Van Effenterre R, Delattre JY, Carpentier AF (2006) Phase 1 trial of a CpG oligodeoxynucleotide for patients with recurrent glioblastoma. Neuro Oncol 8:60-66 (Pubitemid 43154452)
4. Chu E (2012) An update on the current and emerging targeted agents in metastatic colorectal cancer. Clin Colorectal Cancer 11:1-13
5. Chung KY, Gore I, Fong L, Venook A, Beck SB, Dorazio P, Criscitiello PJ, Healey DI, Huang B, Gomez-Navarro J, Saltz LB (2010) Phase II study of the anti-cytotoxic T-lymphocyte-associated antigen 4 monoclonal antibody, tremelimumab, in patients with refractory metastatic colorectal cancer. J Clin Oncol 28:3485-3490
6. Díaz-Rubio E, Gómez-España A, Massutí B, Sastre J, Abad A, Valladares M, Rivera F, Safont MJ, Martínez de Prado P, Gallén M, González E, Marcuello E, Benavides M, Fernández-Martos C, Losa F, Escudero P, Arrivi A, Cervantes A, Dueñas R, López-Ladrón A, Lacasta A, Llanos M, Tabernero JM, Antón A, Aranda E; Spanish Cooperative Group for the Treatment of Digestive Tumors (2012) First-line XELOX plus bevacizumab followed by XELOX plus bevacizumab or single-agent bevacizumab as maintenance therapy in patients with metastatic colorectal cancer: the phase III MACRO TD study. Oncologist 17:15-25
7. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45:228-247
8. Friedberg JW, Kim H, McCauley M, Hessel EM, Sims P, Fisher DC, Nadler LM, Coffman RL, Freedman AS (2005) Combination immunotherapy with a CpG oligonucleotide (1018 ISS) and rituximab in patients with non-Hodgkin lymphoma: increased interferon-alpha/beta-inducible gene expression, without significant toxicity. Blood 105:489-495 (Pubitemid 40070726)
9. Frohlich MW (2012) Sipuleucel-T for the treatment of advanced prostate cancer. Semin Oncol 39:245-252
10. Hales RK, Banchereau J, Ribas A, Tarhini A, Weber JS, Fox BA, Drake CG (2010) Assessing oncologic benefit in clinical trials of immunotherapy agents. Ann Oncol 21:1944-1951
11. Hirsh V, Paz-Ares L, Boyer M, Rosell R, Middleton G, Eberhardt WE, Szczesna A, Reiterer P, Saleh M, Arrieta O, Bajetta E, Webb RT, Raats J, Benner RJ, Fowst C, Meech SJ, Readett D, Schiller JH (2011) Randomized phase III trial of paclitaxel/carboplatin with or without PF-3512676 (Toll-like receptor 9 agonist) as first-line treatment for advanced non-small-cell lung cancer. J Clin Oncol 29:2667-2674
12. Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC, Akerley W, van den Eertwegh AJ, Lutzky J, Lorigan P, Vaubel JM, Linette GP, Hogg D, Ottensmeier CH, Lebbé C, Peschel C, Quirt I, Clark JI, Wolchok JD, Weber JS, Tian J, Yellin MJ, Nichol GM, Hoos A, Urba WJ (2010) Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 363:711-723
13. Kanzler H, Barrat FJ, Hessel EM, Coffman RL (2007) Therapeutic targeting of innate immunity with Toll-like receptor agonists and antagonists. Nat Med 13:552-559 (Pubitemid 46830615)
14. Kirkwood JM, Lorigan P, Hersey P, Hauschild A, Robert C, McDermott D, Marshall MA, Gomez-Navarro J, Liang JQ, Bulanhagui CA (2010) Phase II trial of tremelimumab (CP-675,206) in patients with advanced refractory or relapsed melanoma. Clin Cancer Res 39:245-252
15. Koeberle D, Betticher DC, Von Moos R, Dietrich D, Brauchli P, Baertschi D, Matter-Walstra K, Winterhalder RC, Borner MM, Anchisi S, Moosmann P, Kollar A, Saletti P, Roth A, Frueh M, Kueng M, Popescu RA, Schacher S, Hess V, Herrmann R (2013) Bevacizumab continuation versus no continuation after first-line chemo-bevacizumab therapy in patients with metastatic colorectal cancer: A randomized phase III noninferiority trial (SAKK 41/06). J Clin Oncol 31(suppl; abstr 3503)
16. Koopman M, Simkens L, May A, Mol L, van Tinteren H, Punt CJA, on behalf of the CAIRO3 Study Group (2014) Final results and subgroup analyses of the phase 3 CAIRO3 study: Maintenance treatment with capecitabine and bevacizumab versus observation after induction treatment with chemotherapy and bevacizumab in metastatic colorectal cancer (mCRC). J Clin Oncol 32(suppl 3; abstr LBA388)
17. Krieg AM (2002) CpG motifs in bacterial DNA and their immune effects. Annu Rev Immunol 20:709-760
18. Manegold C, van Zandwijk N, Szczesna A, Zatloukal P, Au JS, Blasinska-Morawiec M, Serwatowski P, Krzakowski M, Jassem J, Tan EH, Benner RJ, Ingrosso A, Meech SJ, Readett D, Thatcher N (2012) A phase III randomized study of gemcitabine and cisplatin with or without PF-3512676 (TLR9 agonist) as first-line treatment of advanced non-small-cell lung cancer. Ann Oncol 23:72-77
19. Pardoll D, Drake C (2012) Immunotherapy earns its spot in the ranks of cancer therapy. J Exp Med 209:201-209
20. Pashenkov M, Goëss G, Wagner C, Hörmann M, Jandl T, Moser A, Britten CM, Smolle J, Koller S, Mauch C, Tantcheva-Poor I, Grabbe S, Loquai C, Esser S, Franckson T, Schneeberger A, Haarmann C, Krieg AM, Stingl G, Wagner SN (2006) Phase II trial of a toll-like receptor 9-activating oligonucleotide in patients with metastatic melanoma. J Clin Oncol 24:5716-5724
21. Ramos FJ, Macarulla T, Capdevila J, Elez E, Tabernero J (2008) Understanding the predictive role of K-ras for epidermal growth factor receptor-targeted therapies in colorectal cancer. Clin Colorectal Cancer 7(Suppl 2):S52-S57
22. Robert C, Thomas L, Bondarenko I, O'Day S, Weber J, Garbe C, Lebbe C, Baurain JF, Testori A, Grob JJ, Davidson N, Richards J, Maio M, Hauschild A, Miller WH Jr, Gascon P, Lotem M, Harmankaya K, Ibrahim R, Francis S, Chen T, Humphrey R, Hoos A, Wolchok JD (2011) Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. N Engl J Med 364:2517-2526
23. Saif MW, Shah M (2009) K-ras mutations in colorectal cancer: a practice changing discovery. Clin Adv Hematol Oncol 7:45-53, 64
24. Schmidt M, Anton K, Nordhaus C, Junghans C, Wittig B, Worm M (2006a) Cytokine and Ig-production by CG-containing sequences with phosphorodiester backbone and dumbbell-shape. Allergy 61:56-63 (Pubitemid 43381192)
25. Schmidt M, Cristobal J, Sander A, Brzezicha B, König-Merediz SA, Wittig B (2006b) dSLIM immunomodulators induce anti-tumor responses both in vitro and in vivo. Mol Ther 13(suppl 1; abstr 426):S164
26. Schmidt M, Brzezicha B, Chen Y, König-Merediz SA, Wittig B (2008) dSLIM immunomodulators reduce tumor growth in various animal tumor models. Mol Ther 16(suppl 1; abstr 935):S1-S389
27. Strickler JH, Hurwitz HI (2012) Maintenance therapy for first-line metastatic colorectal cancer: activity and sustainability. Oncologist 17:9-10
28. Topalian SL, Hodi FS, Brahmer JR et al (2012) Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 366:2443-2454
29. Tournigand C, Samson B, Scheithauer W, Lledo G, Viret F, Andre T, Ramée JF, Tubiana-Mathieu N, Dauba J, Dupuis O, Rinaldi Y, Mabro M, Aucoin N, Khalil A, Latreille J, Louvet C, Brusquant D, Bonnetain F, Chibaudel B, De Gramont A (2012) Bevacizumab (Bev) with or without erlotinib as maintenance therapy, following induction first-line chemotherapy plus Bev, in patients (pts) with metastatic colorectal cancer (mCRC): Efficacy and safety results of the International GERCOR DREAM phase III trial. J Clin Oncol 30(suppl; abstr LBA3500)
30. Weber JS, Kahler KC, Hauschild A (2012) Management of immune-related adverse events and kinetics of response with ipilimumab. J Clin Oncol 30:2691-2697
31. Weihrauch MR, Ansén S, Jurkiewicz E, Geisen C, Xia Z, Anderson KS, Gracien E, Schmidt M, Wittig B, Diehl V, Wolf J, Bohlen H, Nadler LM (2005) Phase I/II combined chemoimmunotherapy with carcinoembryonic antigen-derived HLA-A2-restricted CAP-1 peptide and irinotecan, 5-fluorouracil, and leucovorin in patients with primary metastatic colorectal cancer. Clin Cancer Res 11:5993-6001 (Pubitemid 41170331)
32. Wittig B, Märten A, Dorbic T, Weineck S, Min H, Niemitz S, Trojaneck B, Flieger D, Kruopis S, Albers A, Löffel J, Neubauer A, Albers P, Müller S, Sauerbruch T, Bieber T, Huhn D, Schmidt-Wolf IG (2001) Therapeutic vaccination against metastatic carcinoma by expression-modulated and immunomodified autologous tumor cells: a first clinical phase I/II trial. Hum Gene Ther 12:267-278 (Pubitemid 32163898)
33. Wolchok JD, Hoos A, O'Day S, Weber JS, Hamid O, Lebbé C, Maio M, Binder M, Bohnsack O, Nichol G, Humphrey R, Hodi FS (2009) Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin Cancer Res 15:7412-7420