Safety and activity of the first-in-class Sym004 anti-EGFR antibody mixture in patients with refractory colorectal cancer

Cancer Discovery

Volumn 5, Issue 6, 2015, Pages 598-609

  Dienstmann, Rodrigo ^a,b   Patnaik, Amita ^c   Garcia Carbonero, Rocio ^a   Cervantes, Andrés ^d   Benavent, Marta ^a   Roselló, Susana ^d   Tops, Bastiaan B J ^e   van der Post, Rachel S ^e   Argilés, Guillem ^a   Skartved, Niels J Ø ^f   Hansen, Ulla H ^f   Hald, Rikke ^f   Pedersen, Mikkel W ^f   Kragh, Michael ^f   Horak, Ivan D ^f   Braun, Stephan ^f   Van Cutsem, Eric ^g   Tolcher, Anthony W ^c   Tabernero, Josep ^a  

^a INSTITUTO DE SALUD CARLOS III   (Spain)

^b USA   (United States)

^c South Texas Accelerated Research Therapeutics (START)   (United States)

^d UNIVERSITY OF VALENCIA   (Spain)

^e RADBOUD UNIVERSITY MEDICAL CENTER   (Netherlands)

^f Symphogen AS   (Denmark)

^g UNIVERSITY OF LEUVEN   (Belgium)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIHISTAMINIC AGENT; ANTIPYRETIC AGENT; APC PROTEIN; B RAF KINASE; CETUXIMAB; EPIDERMAL GROWTH FACTOR RECEPTOR 2; EPIDERMAL GROWTH FACTOR RECEPTOR 3; EPIDERMAL GROWTH FACTOR RECEPTOR 4; FUTUXIMAB; GLUCOCORTICOID; K RAS PROTEIN; KI 67 ANTIGEN; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; PANITUMUMAB; PHOSPHATIDYLINOSITOL 3, 4, 5 TRISPHOSPHATE 3 PHOSPHATASE; PHOSPHATIDYLINOSITOL 4, 5 BISPHOSPHATE 3 KINASE; PROTEIN P53; RAF PROTEIN; S6 KINASE; SCATTER FACTOR RECEPTOR; SMAD4 PROTEIN; UNCLASSIFIED DRUG; ANTINEOPLASTIC AGENT; EPIDERMAL GROWTH FACTOR RECEPTOR; LIGAND; MONOCLONAL ANTIBODY; PHOSPHATIDYLINOSITOL 3 KINASE; PIK3CA PROTEIN, HUMAN; SYM004 ANTIBODY;

ADULT; AGED; ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER INHIBITION; CLINICAL ARTICLE; COLORECTAL CANCER; COLORECTAL CANCER CELL LINE; COMPUTER ASSISTED TOMOGRAPHY; CONTROLLED STUDY; DIARRHEA; DOSE RESPONSE; DRUG DOSE ESCALATION; DRUG HALF LIFE; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; DRY SKIN; ENZYME LINKED IMMUNOSORBENT ASSAY; FEMALE; FLUORESCENCE IN SITU HYBRIDIZATION; GENE AMPLIFICATION; GENE MUTATION; HISTOPATHOLOGY; HUMAN; HUMAN CELL; HUMAN TISSUE; HYPOMAGNESEMIA; IMMUNOGENICITY; INFUSION RELATED REACTION; MALE; METASTATIC COLORECTAL CANCER; MIDDLE AGED; MUCOSA INFLAMMATION; MULTICENTER STUDY; NUCLEAR MAGNETIC RESONANCE IMAGING; ONCOGENE H RAS; ONCOGENE N RAS; PHARMACOKINETIC ASSAY; PHASE 1 CLINICAL TRIAL; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; PRURITUS; RASH; SKIN TOXICITY; TREATMENT RESPONSE; TUMOR BIOPSY; VERY ELDERLY; ANTAGONISTS AND INHIBITORS; CLINICAL TRIAL; COLORECTAL NEOPLASMS; GENETICS; METABOLISM; METASTASIS; MUTATION; ONCOGENE RAS; PATHOLOGY; TREATMENT OUTCOME; TUMOR CELL LINE;

ADULT; AGED; AGED, 80 AND OVER; ANTIBODIES, MONOCLONAL; ANTINEOPLASTIC AGENTS; CELL LINE, TUMOR; COLORECTAL NEOPLASMS; DOSE-RESPONSE RELATIONSHIP, DRUG; FEMALE; GENE AMPLIFICATION; GENES, RAS; HUMANS; LIGANDS; MALE; MIDDLE AGED; MUTATION; NEOPLASM METASTASIS; PHOSPHATIDYLINOSITOL 3-KINASES; PROTO-ONCOGENE PROTEINS B-RAF; RECEPTOR, EPIDERMAL GROWTH FACTOR; TREATMENT OUTCOME;

EID: 84932608425     PISSN: 21598274     EISSN: 21598290     Source Type: Journal    
DOI: 10.1158/2159-8290.CD-14-1432     Document Type: Article

References (28)

1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin 2015;65:5.29.
2. Van Cutsem E, Kohne CH, Hitre E, Zaluski J, Chang Chien CR, Makhson A, et al. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med 2009; 360: 1408. 17.
3. Douillard JY, Siena S, Cassidy J, Tabernero J, Burkes R, Barugel M, et al. Randomized, phase III trial of panitumumab with infusional fl uorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as fi rst line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study. J Clin Oncol 2010; 28: 4697. 705.
4. Douillard JY, Oliner KS, Siena S, Tabernero J, Burkes R, Barugel M, et al. Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer. N Engl J Med 2013; 369: 1023.34.
5. Amado R, Wolf M, Peeters M, Van Cutsem E, Siena S, Freeman D, et al. Wild-type KRAS is required for panitumumab effi cacy in patients with metastatic colorectal cancer. J Clin Oncol 2008; 26: 1626. 34.
6. Karapetis C, Khambata-Ford S, Jonker D, O’Callaghan C, Tu D, Tebbutt N, et al. K-ras mutations and benefi t from cetuximab in advanced colorectal cancer. N Engl J Med 2008; 359: 1757. 65.
7. Lida M, Brand TM, Starr MM, Li C, Huppert EJ, Luthar N, et al. Sym004, a novel EGFR antibody mixture, can overcome acquired resistance to cetuximab. Neoplasia 2013; 15: 1196. 206.
8. Diaz LA Jr, Williams RT, Wu J, Kinde I, Hecht JR, Berlin J, et al. The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancers. Nature 2012; 486: 537. 40.
9. Misale S, Yaeger R, Hobor S, Scala E, Janakiraman M, Liska D, et al. Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer. Nature 2012; 486: 532. 6.
10. Troiani T, Martinelli E, Napolitano S, Vitagliano D, Ciuffreda LP, Costantino S, et al. Increased TGF-α as a mechanism of acquired resistance to the anti-EGFR inhibitor cetuximab through EGFR-MET interaction and activation of MET signaling in colon cancer cells. Clin Cancer Res 2013; 19: 6751. 65.
11. Hobor S , Van Emburgh BO , Crowley E , Misale S , Di Nicolantonio F , Bardelli A. TGFalpha and amphiregulin paracrine network promotes resistance to EGFR blockade in colorectal cancer cells. Clin Cancer Res 2014; 20: 6429. 38.
12. Kawakami H , Okamoto I, Yonesaka K, Okamoto K, Shibata K, Shinkai Y, et al. The anti-HER3 antibody patritumab abrogates cetuximab resistance mediated by heregulin in colorectal cancer cells. Oncotarget 2014; 5: 11847. 56.
13. Tabernero J , Cervantes A, Rivera F, Martinelli E, Rojo F, von Heydebreck A, et al. Pharmacogenomic and pharmacoproteomic studies of cetuximab in metastatic colorectal cancer: biomarker analysis of a phase I dose-escalation study. J Clin Oncol 2010; 28: 1181. 9.
14. Montagut C, Dalmases A, Bellosillo B, Crespo M, Pairet S, Iglesias M, et al. Identifi cation of a mutation in the extracellular domain of the Epidermal Growth Factor Receptor conferring cetuximab resistance in colorectal cancer. Nat Med 2012; 18: 221. 3.
15. Arena S, Bellosillo B, Siravegna G, Martinez A, Canadas I, Lazzari L, et al. Emergence of multiple EGFR extracellular mutations during cetuximab treatment in colorectal cancer. Clin Cancer Res 2015 Jan 26. [Epub ahead of print].
16. Huang S, Churong L, Armstrong EA, Peet CR, Saker J, Amler L C, et al. Dual targeting of EGFR and HER3 with MEHD7945A overcomes acquired resistance to EGFR inhibitors and radiation. Cancer Res 2012; 73: 824. 33.
17. Pedersen MW , Jacobsen HJ, Koefoed K, Hey A, Pyke C, Haurum JS, et al. Sym004: a novel synergistic anti-epidermal growth factor receptor antibody mixture with superior anticancer effi cacy. Cancer Res 2010; 70: 588. 97
18. Koefoed K, Steinaa L, Søderberg JN, Kjær I, Jacobsen HJ, Meijer PJ, et al. Rational identifi cation of an optimal antibody mixture for targeting the epidermal growth factor receptor. MAbs 2011; 3: 584-95.
19. Skartved NJ, Jacobsen HJ, Pedersen MW, Jensen PF, Sen JW, Jørgensen TK, et al. Preclinical pharmacokinetics and safety of Sym004: a synergistic antibody mixture directed against epidermal growth factor receptor. Clin Cancer Res 2011; 17: 5962-72.
20. Saif MW, Kaley K, Chu E, Copur MS. Safety and effi cacy of panitumumab therapy after progression with cetuximab: experience at two institutions. Clin Colorectal Cancer 2010; 9: 315-8.
21. Wadlow RC, Hezel AF, Abrams TA, Blaszkowsky LS, Fuchs CS, Kulke- MH, et al. Panitumumab in patients with KRAS wild-type colorectal cancer after progression on cetuximab. Oncologist 2012; 17: 14.
22. Peeters M, Oliner KS, Parker A, Siena S, Van Cutsem E, Huang J, et al. Massively parallel tumor multigene sequencing to evaluate response to panitumumab in a randomized phase III study of metastatic colorectal cancer. Clin Cancer Res 2013; 19: 1902-12.
23. S adanandam A, Lyssiotis CA, Homicsko K, Collisson EA, Gibb WJ, Wullschleger S , et al. A colorectal cancer classifi cation system that associates cellular phenotype and responses to therapy. Nat Med 2013; 19: 619-25.
24. Ebi H, Corcoran RB, Singh A, Chen Z, Song Y, Lifshits E, et al. Receptor tyrosine kinases exert dominant control over PI3K signaling in human KRAS mutant colorectal cancers. J Clin Invest 2011; 121: 4311-21.
25. Julien S, Merino-Trigo A, Lacroix L, Pocard M, Goéré D, Mariani P, et al. Characterization of a large panel of patient-derived tumor xenografts representing the clinical heterogeneity of human colorectal cancer. Clin Cancer Res 2012; 18: 5314-28.
26. Brattain MG, Levine AE, Chakrabarty S, Yeoman LC, Willson JK, Long B Heterogeneity of human colon carcinoma. Cancer Metastasis Rev 1984; 3: 177-91.
27. Shankar G, Devanarayan V, Amaravadi L, Barrett YC, Bowsher R, Finco-Kent D, et al. Recommendations for the validation of immunoassays used for detection of host antibodies against biotechnology products. J Pharm Biomed Anal 2008; 48: 1267-81.
28. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009; 45: 228-47.