Ramucirumab (IMC-1121B): A novel attack on angiogenesis

Future Oncology

Volumn 6, Issue 7, 2010, Pages 1085-1094

  Spratlin, Jennifer L ^a   Mulder, Karen E ^a   MacKey, John R ^a  

^a CROSS CANCER INSTITUTE   (Canada)

Author keywords

angiogenesis; antiangiogenic agent; IMC 1121B; monoclonal antibody; VEGFR2

Indexed keywords

ANGIOGENESIS INHIBITOR; BEVACIZUMAB; CEDIRANIB; IMC 1121B; MATRIX METALLOPROTEINASE; MONOCLONAL ANTIBODY; PLATELET DERIVED GROWTH FACTOR BETA RECEPTOR; RAMUCIRUMAB; SORAFENIB; SUNITINIB; TRANSFORMING GROWTH FACTOR; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; VANDETANIB; VASCULOTROPIN RECEPTOR 2;

ABDOMINAL CRAMP; ACUTE KIDNEY FAILURE; ALOPECIA; AMYLASE BLOOD LEVEL; ANEMIA; ANGIOGENESIS; ANOREXIA; ASTHENIA; BILIRUBIN BLOOD LEVEL; BLOOD VESSEL PERMEABILITY; BRAIN DISEASE; BRAIN HEMORRHAGE; BREAST CANCER; BRONCHOSPASM; BULLOUS SKIN DISEASE; CANCER IMMUNOTHERAPY; CANCER THERAPY; CARDIOPULMONARY INSUFFICIENCY; CLINICAL TRIAL; COLITIS; COLORECTAL CANCER; CONGESTIVE HEART FAILURE; DEEP VEIN THROMBOSIS; DESQUAMATION; DIARRHEA; DRUG MECHANISM; DRUG METABOLISM; DRUG SAFETY; DRUG TOLERABILITY; DUODENAL ULCER BLEEDING; DYSPHONIA; DYSPNEA; EDEMA; EPISTAXIS; FATIGUE; FEBRILE NEUTROPENIA; FISTULA; FLUSHING; FOLLICULITIS; GASTROINTESTINAL HEMORRHAGE; GLIOBLASTOMA; HAND FOOT SYNDROME; HEADACHE; HEART ARREST; HEART INFARCTION; HEART LEFT VENTRICLE EJECTION FRACTION; HEMOPTYSIS; HUMAN; HYPERTENSION; HYPERTENSIVE CRISIS; HYPOGLYCEMIA; HYPOPHOSPHATEMIA; HYPOTENSION; INTESTINE ISCHEMIA; INTESTINE OBSTRUCTION; INTESTINE PERFORATION; KIDNEY CARCINOMA; LEUKOPENIA; LIVER FAILURE; LUNG EMBOLISM; LUNG NON SMALL CELL CANCER; NAUSEA; NEUTROPENIA; NONHUMAN; PELVIC VENOUS THROMBOSIS; PERIPHERAL NEUROPATHY; PHLEBITIS; PLEURITIC PAIN; PNEUMOTHORAX; PRIORITY JOURNAL; PROCTALGIA; PROTEINURIA; RASH; RESPIRATORY FAILURE; RETROSTERNAL PAIN; REVIEW; SEPSIS; SIDE EFFECT; SKIN TOXICITY; SOLID TUMOR; SUPRAVENTRICULAR TACHYCARDIA; SYNCOPE; THORAX PAIN; THROMBOCYTOPENIA; TRIACYLGLYCEROL LIPASE BLOOD LEVEL; TUMOR BLEEDING; TUMOR FLARE; TUMOR NECROSIS; UVULA EDEMA; VOMITING; NEOVASCULARIZATION, PATHOLOGIC; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); SAFETY;

ANGIOGENESIS INHIBITORS; ANTIBODIES, MONOCLONAL; CLINICAL TRIALS, PHASE I AS TOPIC; CLINICAL TRIALS, PHASE II AS TOPIC; CLINICAL TRIALS, PHASE III AS TOPIC; HUMANS; NEOVASCULARIZATION, PATHOLOGIC; SAFETY;

EID: 77954682879     PISSN: 14796694     EISSN: 17448301     Source Type: Journal    
DOI: 10.2217/fon.10.75     Document Type: Review

References (67)

1. Klagsbrun M, DAmore PA: Vascular endothelial growth factor and its receptors. Cytokine Growth Factor Rev. 7(3), 259-270 (1996).
2. Neufeld G, Cohen T, Gengrinovitch S, Poltorak Z: Vascular endothelial growth factor (VEGF) and its receptors. FASEB J. 13(1), 9-22 (1999).
3. Ferrara N: Molecular and biological properties of vascular endothelial growth factor. J. Mol. Med. 77(7), 527-543 (1999). (Pubitemid 29426311)
4. Aguayo A, Kantarjian H, Manshouri T, et al.: Angiogenesis in acute and chronic leukemias and myelodysplastic syndromes. Blood 96(6), 2240-2245 (2000).
5. Carmeliet P, Jain RK: Angiogenesis in cancer and other diseases. Nature 407(6801), 249-257 (2000).
6. Leung DW, Cachianes G, Kuang WJ, Goeddel DV, Ferrara N: Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 246(4935), 1306-1309 (1989).
7. Inoue M, Hager JH, Ferrara N, Gerber HP, Hanahan D: VEGF-A has a critical, nonredundant role in angiogenic switching and pancreatic b cell carcinogenesis. Cancer Cell 1(2), 193-202 (2002).
8. De Vries C, Escobedo JA, Ueno H, Houck K, Ferrara N, Williams LT: The fms-like tyrosine kinase, a receptor for vascular endothelial growth factor. Science 255(5047), 989-991 (1992).
9. Shibuya M, Yamaguchi S, Yamane A, et al.: Nucleotide sequence and expression of a novel human receptor-type tyrosine kinase gene (FLT) closely related to the fms family. Oncogene 5(4), 519-524 (1990).
10. Plate KH, Breier G, Weich HA, Mennel HD, Risau W: Vascular endothelial growth factor and glioma angiogenesis: coordinate induction of VEGF receptors, distribution of VEGF protein and possible in vivo regulatory mechanisms. Int. J. Cancer 59(4), 520-529 (1994).
11. Li B, Fuh G, Meng G, et al.: Receptor-selective variants of human vascular endothelial growth factor. Generation and characterization. J. Biol. Chem. 275(38), 29823-29828 (2000).
12. Gille H, Kowalski J, Li B, et al.: Analysis of biological effects and signaling properties of Flt-1 (VEGFR-1) and KDR (VEGFR-2). A reassessment using novel receptor-specific vascular endothelial growth factor mutants. J. Biol. Chem. 276(5), 3222-3230 (2001).
13. Gerber HP, Ferrara N: The role of VEGF in normal and neoplastic hematopoiesis. J. Mol. Med. 81(1), 20-31 (2003).
14. Witte L, Hicklin DJ, Zhu Z, et al.: Monoclonal antibodies targeting the VEGF receptor-2 (Flk1/KDR) as an antiangiogenic therapeutic strategy. Cancer Metastasis Rev. 17(2), 155-161 (1998).
15. Zhu Z, Witte L: Inhibition of tumor growth and metastasis by targeting tumor-associated angiogenesis with antagonists to the receptors of vascular endothelial growth factor. Invest. New Drugs 17(3), 195-212 (1999).
16. Zhu Z, Bohlen P, Witte L: Clinical development of angiogenesis inhibitors to vascular endothelial growth factor and its receptors as cancer therapeutics. Curr. Cancer Drug Targets 2(2), 135-156 (2002).
17. Abdelrahim M, Konduri S, Basha R, Philip PA, Baker CH: Angiogenesis: an update and potential drug approaches (review). Int. J. Oncol. 36(1), 5-18 (2010).
18. Imclone Systems Ioncorprated: Investigators brochure (2008).
19. Hurwitz H, Fehrenbacher L, Novotny W, et al.: Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N. Engl. J. Med. 350(23), 2335-2342 (2004).
20. Saltz LB, Clarke S, Diaz-Rubio E, et al.: Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized Phase III study. J. Clin. Oncol. 26(12), 2013-2019 (2008).
21. Giantonio BJ, Catalano PJ, Meropol NJ, et al.: Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200. J. Clin. Oncol. 25(12), 1539-1544 (2007).
22. Sandler A, Gray R, Perry MC, et al.: Paclitaxel- carboplatin alone or with bevacizumab for non-small-cell lung cancer. N. Engl. J. Med. 355(24), 2542-2550 (2006).
23. Kumar R, Knick VB, Rudolph SK, et al.: Pharmacokinetic-pharmacodynamic correlation from mouse to human with pazopanib, a multikinase angiogenesis inhibitor with potent antitumor and antiangiogenic activity. Mol. Cancer Ther. 6(7), 2012-2021 (2007).
24. Friedman HS, Prados MD, Wen PY, et al.: Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J. Clin. Oncol. 27(28), 4733-4740 (2009).
25. Rini BI, Halabi S, Rosenberg JE, et al.: Bevacizumab plus interferon a compared with interferon a monotherapy in patients with metastatic renal cell carcinoma: CALGB 90206. J. Clin. Oncol. 26(33), 5422-5428 (2008).
26. Motzer RJ, Hutson TE, Tomczak P, et al.: Sunitinib versus interferon a in metastatic renal-cell carcinoma. N. Engl. J. Med. 356(2), 115-124 (2007). (Pubitemid 46089672)
27. Demetri GD, van Oosterom AT, Garrett CR, et al.: Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet 368(9544), 1329-1338 (2006).
28. Escudier B, Eisen T, Stadler WM, et al.: Sorafenib in advanced clear-cell renal-cell carcinoma. N. Engl. J. Med. 356(2), 125-134 (2007).
29. Llovet J, Ricci S, Mazzaferro V, et al.: Sorafenib improves survival in advanced hepatocellular carcinoma (HCC): results of a Phase III randomized placebo-controlled trial (SHARP trial). J. Clin. Oncol. 2007 ASCO Annual Meeting Proceedings Part I 25(Suppl. 18), LBA1 (2007).
30. Mendel DB, Laird AD, Xin X, et al.: In vivo antitumor activity of su11248, a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor and platelet-derived growth factor receptors: determination of a pharmacokinetic/ pharmacodynamic relationship. Clin. Cancer Res. 9(1), 327-337 (2003).
31. Chow LQ, Eckhardt SG: Sunitinib: from rational design to clinical efficacy. J. Clin. Oncol. 25(7), 884-896 (2007).
32. Bergers G, Brekken R, McMahon G, et al.: Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis. Nat. Cell Biol. 2(10), 737-744 (2000).
33. Motzer RJ, Hutson TE, Tomczak P, et al.: Overall survival and updated results for sunitinib compared with interferon a in patients with metastatic renal cell carcinoma. J. Clin. Oncol. 27(22), 3584-3590 (2009).
34. Chang YS, Adnane J, Trail PA, et al.: Sorafenib (BAY 43-9006) inhibits tumor growth and vascularization and induces tumor apoptosis and hypoxia in RCC xenograft models. Cancer Chemother. Pharmacol. 59(5), 561-574 (2007).
35. Strumberg D: Preclinical and clinical development of the oral multikinase inhibitor sorafenib in cancer treatment. Drugs Today (Barc.) 41(12), 773-784 (2005). (Pubitemid 43333354)
36. Posey JA, Ng TC, Yang B, et al.: A Phase I study of antikinase insert domain-containing receptor antibody, IMC-1C11, in patients with liver metastases from colorectal carcinoma. Clin. Cancer Res. 9(4), 1323-1332 (2003).
37. Jayson GC, Ton C, Parker GJ, et al.: Phase I and DCE-MRI evaluation of CDP791, a di-Fab PEG conjugate that inhibits VEGFR2. J. Clin. Oncol. 2007 ASCO Annual Meeting Proceedings Part I 25(Suppl. 18), 3523 (2007).
38. Ton NC, Parker GJ, Jackson A, et al.: Phase I evaluation of CDP791, a pegylated di-Fab́ conjugate that binds vascular endothelial growth factor receptor 2. Clin. Cancer Res. 13(23), 7113-7118 (2007).
39. Spratlin JL, Cohen RB, Eadens M, et al.: Phase I pharmacologic and biologic study of ramucirumab (IMC-1121b), a fully human immunoglobulin G1 monoclonal antibody targeting the vascular endothelial growth factor receptor-2. J. Clin. Oncol. 28(5), 780-787 (2010).
40. Chiorean E, Sweeney C, Hurwitz H, et al.: Phase I dose-escalation study of the antiVEGFR-2 recombinant human IGG1 monoclonal antibody (mAb) IMC-1121b, administered every other week (q2w) or every 3 weeks (q3w) in patients (pts) with advanced cancers, abstract B15. In: Molecular Targets and Cancer Therapeutics. American Association of Clinical Research, CA, USA (2007).
41. Lu D, Jimenez X, Zhang H, Bohlen P, Witte L, Zhu Z: Selection of high affinity human neutralizing antibodies to VEGFR2 from a large antibody phage display library for antiangiogenesis therapy. Int. J. Cancer 97(3), 393-399 (2002).
42. De Haard HJ, van Neer N, Reurs A, et al.: A large non-immunized human Fab fragment phage library that permits rapid isolation and kinetic analysis of high affinity antibodies. J. Biol. Chem. 274(26), 18218-18230 (1999).
43. Lu D, Shen J, Vil MD, et al.: Tailoring in vitro selection for a picomolar affinity human antibody directed against vascular endothelial growth factor receptor 2 for enhanced neutralizing activity. J. Biol. Chem. 278(44), 43496-43507 (2003). (Pubitemid 37345973)
44. Skobe M, Rockwell P, Goldstein N, Vosseler S, Fusenig NE: Halting angiogenesis suppresses carcinoma cell invasion. Nat. Med. 3(11), 1222-1227 (1997).
45. Prewett M, Huber J, Li Y, et al.: Antivascular endothelial growth factor receptor (fetal liver kinase 1) monoclonal antibody inhibits tumor angiogenesis and growth of several mouse and human tumors. Cancer Res. 59(20), 5209-5218 (1999).
46. Bruns CJ, Liu W, Davis DW, et al.: Vascular endothelial growth factor is an in vivo survival factor for tumor endothelium in a murine model of colorectal carcinoma liver metastases. Cancer 89(3), 488-499 (2000).
47. Hicklin DJ, Witte L, Zhu Z, et al.: Monoclonal antibody strategies to block angiogenesis. Drug Discov. Today 6(10), 517-528 (2001).
48. Imclone Systems Incorporated: Investigators brochure (2009).
49. Zhu Z, Hattori K, Zhang H, et al.: Inhibition of human leukemia in an animal model with human antibodies directed against vascular endothelial growth factor receptor 2. Correlation between antibody affinity and biological activity. Leukemia 17(3), 604-611 (2003). (Pubitemid 36395655)
50. Garcia J, Hudes G, Choueiri T, et al.: Phase II study of IMC-1121b in patients with metastatic renal cell carcinoma (mRCC) following failure of VEGFR-2 tyrosine kinase inhibitor (TKI) therapy: interim results (IMCl CP12-0605/nct00515697). Presented at: European Society for Medical Oncology Congress 2009. Berlin, Germany, 20-24 September 2009.
51. Jayson GC, Zweit J, Jackson A, et al.: Molecular imaging and biological evaluation of humv833 antiVEGF antibody: implications for trial design of antiangiogenic antibodies. J. Natl Cancer Inst. 94(19), 1484-1493 (2002).
52. Thomas AL, Morgan B, Horsfield MA, et al.: Phase I study of the safety, tolerability, pharmacokinetics, and pharmacodynamics of PTK787/ZK 222584 administered twice daily in patients with advanced cancer. J. Clin. Oncol. 23(18), 4162-4171 (2005).
53. Liu G, Rugo HS, Wilding G, et al.: Dynamic contrast-enhanced magnetic resonance imaging as a pharmacodynamic measure of response after acute dosing of ag-013736, an oral angiogenesis inhibitor, in patients with advanced solid tumors: results from a Phase I study. J. Clin. Oncol. 23(24), 5464-5473 (2005).
54. Morgan B, Thomas AL, Drevs J, et al.: Dynamic contrast-enhanced magnetic resonance imaging as a biomarker for the pharmacological response of PTK787/ ZK 222584, an inhibitor of the vascular endothelial growth factor receptor tyrosine kinases, in patients with advanced colorectal cancer and liver metastases: results from two Phase I studies. J. Clin. Oncol. 21(21), 3955-3964 (2003).
55. Gordon MS, Margolin K, Talpaz M, et al.: Phase I safety and pharmacokinetic study of recombinant human antivascular endothelial growth factor in patients with advanced cancer. J. Clin. Oncol. 19(3), 843-850 (2001).
56. Strumberg D, Richly H, Hilger RA, et al.: Phase I clinical and pharmacokinetic study of the novel raf kinase and vascular endothelial growth factor receptor inhibitor BAY 43-9006 in patients with advanced refractory solid tumors. J. Clin. Oncol. 23(5), 965-972 (2005).
57. Moore M, Hirte HW, Siu L, et al.: Phase I study to determine the safety and pharmacokinetics of the novel raf kinase and VEGFR inhibitor BAY 43-9006, administered for 28 days on/7 days off in patients with advanced, refractory solid tumors. Ann. Oncol. 16(10), 1688-1694 (2005).
58. Awada A, Hendlisz A, Gil T, et al.: Phase I safety and pharmacokinetics of BAY 43-9006 administered for 21 days on/7 days off in patients with advanced, refractory solid tumours. Br J. Cancer 92(10), 1855-1861 (2005).
59. Faivre S, Delbaldo C, Vera K, et al.: Safety, pharmacokinetic, and antitumor activity of su11248, a novel oral multitarget tyrosine kinase inhibitor, in patients with cancer. J. Clin. Oncol. 24(1), 25-35 (2006).
60. Britten CD, Kabbinavar F, Hecht JR, et al.: A Phase I and pharmacokinetic study of sunitinib administered daily for 2 weeks, followed by a 1-week off period. Cancer Chemother. Pharmacol. 61(3), 515-524 (2007).
61. Holden SN, Eckhardt SG, Basser R, et al.: Clinical evaluation of ZD6474, an orally active inhibitor of VEGF and EGF receptor signaling, in patients with solid, malignant tumors. Ann. Oncol. 16(8), 1391-1397 (2005).
62. Drevs J, Siegert P, Medinger M, et al.: Phase I clinical study of AZD2171, an oral vascular endothelial growth factor signaling inhibitor, in patients with advanced solid tumors. J. Clin. Oncol. 25(21), 3045-3054 (2007).
63. Ryan CJ, Stadler WM, Roth B, et al.: Phase I dose escalation and pharmacokinetic study of AZD2171, an inhibitor of the vascular endothelial growth factor receptor tyrosine kinase, in patients with hormone refractory prostate cancer (HRPC). Invest. New Drugs 25(5), 445-451 (2007).
64. Ritter MR, Butschek RA, Friedlander M, Friedlander SF: Pathogenesis of infantile haemangioma: new molecular and cellular insights. Expert Rev. Mol. Med. 9(32), 1-19 (2007).
65. Wilhelm SM, Carter C, Tang L, et al.: BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res. 64(19), 7099-7109 (2004).
66. Clark JW, Eder JP, Ryan D, Lathia C, Lenz HJ: Safety and pharmacokinetics of the dual action Raf kinase and vascular endothelial growth factor receptor inhibitor, BAY 43-9006, in patients with advanced, refractory solid tumors. Clin. Cancer Res. 11(15), 5472-5480 (2005).
67. Tamura T, Minami H, Yamada Y, et al.: A Phase I dose-escalation study of ZD6474 in Japanese patients with solid, malignant tumors. J. Thorac. Oncol. 1(9), 1002-1009 (2006). (Pubitemid 47181370)