Phase 2, open-label, 1:1 randomized controlled trial exploring the efficacy of EMD 1201081 in combination with cetuximab in second-line cetuximab-naïve patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN)

Investigational New Drugs

Volumn 32, Issue 6, 2014, Pages 1278-1284

  Ruzsa, A ^a   Sen, M ^b   Evans, M ^c   Lee, L W ^d   Hideghety, K ^e   Rottey, S ^f   Klimak, P ^g   Holeckova, P ^h   Fayette, J ⁱ   Csoszi, T ^j   Erfan, J ^k   Forssmann, U ^l,m   Goddemeier, T ^m   Bexon, A ⁿ   Nutting, C ^o  

^a Zala Megyei Korhaz   (Hungary)

^b St James's Institute of Oncology   (United Kingdom)

^c VELINDRE CANCER CENTRE   (United Kingdom)

^d CHRISTIE HOSPITAL   (United Kingdom)

^e UNIVERSITY OF SZEGED   (Hungary)

^f GHENT UNIVERSITY HOSPITAL   (Belgium)

^g Nemocnice Kladno   (Czech Republic)

^h CHARLES UNIVERSITY   (Czech Republic)

ⁱ CENTRE LÉON BÉRARD   (France)

^j Jasz Nagykun Szolnok Megyei Hetenyi Geza Korhaz Rendelointezet ^*  (Hungary)

^k Josa Andras Teaching Hospital   (Hungary)

^l BAYER PHARMA AG   (Germany)

^m MERCK SERONO S A   (Switzerland)

ⁿ HYBRIDON INC   (United States)

^o ROYAL MARSDEN HOSPITAL   (United Kingdom)

more..

Author keywords

Cetuximab; Epidermal growth factor receptor neu receptor; Head and neck cancer; Oligonucleotide; Randomized phase 2; Recurrent metastatic; Squamous cell carcinoma; Toll like receptor 9

Indexed keywords

ANTINEOPLASTIC AGENT; CETUXIMAB; IMO-2055; MONOCLONAL ANTIBODY; OLIGONUCLEOTIDE;

CANCER STAGING; CARCINOMA, SQUAMOUS CELL; CLINICAL TRIAL; CONTROLLED STUDY; DISEASE FREE SURVIVAL; FEMALE; HEAD AND NECK NEOPLASMS; HUMAN; MALE; MIDDLE AGED; NEOPLASM RECURRENCE, LOCAL; PHASE 2 CLINICAL TRIAL; RANDOMIZED CONTROLLED TRIAL;

ANTIBODIES, MONOCLONAL, HUMANIZED; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; CARCINOMA, SQUAMOUS CELL; DISEASE-FREE SURVIVAL; FEMALE; HEAD AND NECK NEOPLASMS; HUMANS; MALE; MIDDLE AGED; NEOPLASM RECURRENCE, LOCAL; OLIGONUCLEOTIDES; RESPONSE EVALUATION CRITERIA IN SOLID TUMORS;

EID: 84938680387     PISSN: 01676997     EISSN: 15730646     Source Type: Journal    
DOI: 10.1007/s10637-014-0117-2     Document Type: Article

References (27)

1. Ahmed SM, Cohen EEW (2007) Treatment of squamous cell carcinoma of the head and neck in the metastatic and refractory settings: advances in chemotherapy and the emergence of small molecule epidermal growth factor receptor kinase inhibitors. Curr Cancer Drug Targets 7:666-73
2. Globocan 2012: http://globocan.iarc.fr/old/bar-sex-site-prev.asp?selection=11100&selection=13010&selection=21030&title=Larynx%2C+Lip%2C+oral+cavity%2C+Other+pharynx&statistic=1&populations=6&window=1&grid=1&info=1&color1=5&color1e=&color2=4&color2e=&submit=%C2%A0Execute; downloaded 13 April 2014
3. Bernier J, Domenge C, Ozsahin M, Matuszewska K, Lefèbvre JL, Greiner RH (2004) Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med 350:1945-1952. doi: 10.1056/NEJMoa032641
4. Cooper JS, Pajak TF, Forastiere AA, Jacobs J, Campbell BH, Saxman SB (2004) Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med 350:1937-1944. doi: 10.1056/NEJMoa032646
5. Zimmermann M, Zouhair A, Azria D, Ozsahin M (2006) The epidermal growth factor receptor (EGFR) in head and neck cancer: its role and treatment implications. Radiat Oncol 1:11. doi: 10.1186/1748-717X-1-11 DOI:10.1186%2F1748-717X-1-11#pmc-ext
6. Bonner JA, Harari PM, Giralt J, Cohen RB, Jones CU, Sur RK (2010) Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival. Lancet Oncol 11(1):21-28
7. Vermorken JB, Mesia R, Rivera F, Remenar E, Kawecki A, Rottey S (2008) Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med 359:1116-11127. doi: 10.1056/NEJMoa0802656
8. Vermorken JB, Trigo J, Hitt R, Koralewski P, Diaz-Rubio E, Rolland F (2007) Open-label, uncontrolled, multicenter phase II study to evaluate the efficacy and toxicity of cetuximab as a single agent in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck who failed to respond to platinum-based therapy. J Clin Oncol 25:2171-2177
9. Damiano V, Caputo R, Bianco R, D'Armiento FP, Leonardi A, De Placido S (2006) Novel toll-like receptor 9 agonist induces epidermal growth factor receptor (EGFR) inhibition and synergistic antitumor activity with EGFR inhibitors. Clin Cancer Res 12:577-583
10. Takeda K, Akira S (2005) Toll-like receptors in innate immunity. Int Immunol 17(1):1-14
11. Wickelgren I (2006) Targeting the tolls. Science 312:184-187
12. Wang D, Li Y, Yu D, Song SS, Kandimalla ER, Agrawal S (2004) Immunopharmacological and antitumor effects of second-generation immunomodulatory oligonucleotides containing synthetic CpR motifs. Int J Oncol 24:901-908
13. Damiano V, Caputo R, Garofalo S, Bianco R, Rosa R, Merola G et al (2007) TLR9 agonist acts by different mechanisms synergizing with bevacizumab in sensitive and cetuximab-resistant colon cancer xenografts. PNAS 104(30):12468-12473
14. Rosa R, Melisi D, Damiano V, Bianco R, Garofalo S, Gelardi T et al (2011) Toll-like receptor 9 agonist IMO cooperates with cetuximab in K-ras mutant colorectal and pancreatic cancers. Clin Cancer Res 17(20):6531-6541. doi: 10.1158/1078-0432.CCR-10-3376
15. Moore DJ, Hwang J, McGreivy J, Park S, Malik S, Martin RR et al (2005) Phase I trial of escalating doses of the TLR9 agonist HYB2055 in patients with advanced solid tumors. J Clin Oncol 23(16S):2503
16. Kuzel T, Dutcher J, Ebbinghaus S, Gordon, M, Grubbs, S, Khan, K, et al. (2009) A phase 2 multicenter, randomized, open-label study of two dose levels of IMO-2055 in patients with metastatic or recurrent renal cell carcinoma. Poster presented at the 8th International Kidney Cancer Symposium, Sep 25-26 2009, Chicago, IL, USA
17. Malik S, Hwang J, Cotarla I, Sullivan T, Karr R, Marshall J et al (2007) Initial phase 1 results of gemcitabine, carboplatin and IMO-2055, a toll like receptor 9 (TLR9) agonist, in patients (pts) with advanced solid tumors. J Thor Oncol 2(8):S726-S727. doi: 10.1097/01.JTO.0000284088.13204.12
18. Smith DA, Conkling P, Richards DA, Flores MR, Nemunaitis JJ, Boyd TE et al. (2012) Efficacy and safety of IMO-2055, a novel T LR9 agonist, in combination with erlotinib (E) and bevacizumab (bev) in patients (pts) with advanced or metastatic non-small cell lung cancer (NSCLC) who have progressed following prior chemotherapy. J Clin Oncol 30, (suppl; abstr e18047)
19. Machiels JP, Kaminsky MC, Keller U, Brümmendorf TH, Goddemeier T, Forssmann U, et al.. (2013) Phase Ib trial of IMO-2055 in combination with 5-FU, cisplatin and cetuximab as first-line palliative treatment in patients with recurrent/metastatic squamous cell carcinoma of the head and neck. Invest New Drugs: Feb 10 [Epub ahead of print]
20. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L et al (2000) New Guidelines to evaluate the response to treatment in solid tumors (RECIST Guidelines). J Natl Cancer Inst 92:205-216. doi: 10.1093/jnci/92.3.205
21. CTCAE (Common Terminology Criteria for Adverse Events) (2003), Version 3.0, 12 December 2003
22. Manegold C, van Zandwijk N, Szczesna A, Zatloukal P, Au JS, Blasinska-Morawiec M et al (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(1):72-77. doi: 10.1093/annonc/mdr030
23. Hirsh V, Boyer M, Rosell R, Rosell R, Middleton G, Eberhardt WE, et al. (2008) Randomized phase III trial of paclitaxel/carboplatin with or without PF-3512676 as first line treatment of advanced non-small cell lung cancer (NSCLC). J Clin Oncol 26: (May 20 suppl; abstr 8016)
24. Manegold C, Gravenor D, Woytowitz D, Mezger J, Hirsh V, Albert G et al (2008) Randomized phase II trial of a toll-like receptor 9 agonist oligodeoxynucleotide, PF-3512676, in combination with first-line taxane plus platinum chemotherapy for advanced-stage Non-small-cell lung cancer. J Clin Oncol 26(24):3979-3986
25. Hirsh V, Paz-Ares L, Boyer M, Rosell R, Middleton G, Eberhardt WE et al (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(19):2667-2674. doi: 10.1200/JCO.2010.32.8971
26. Rodriguez-Torres M, Ghalib RH, Gordon SC, E Lawitz, Patel K, Pruitt R, et al. (2010) IMO-2125, A TLR9 Agonist, Induces Immune Responses Which Correlate With Reductions In Viral Load In Null Responder HCV Patients. Hepatology, 52 (4 - Suppl), October abstr 33, 336A
27. Dynavax-FDA advisory committee briefing materials provided prior to the 15 November 2012 meeting of the Vaccines and Related Biological Products Advisory Committee