Investigational antibody-drug conjugates for hematological malignancies

Expert Opinion on Investigational Drugs

Volumn 20, Issue 1, 2011, Pages 75-85

  Polson, Andrew G ^a   Ho, William Y ^a   Ramakrishnan, Vanitha ^a  

^a GENENTECH INC   (United States)

Author keywords

ADCs; antibody drug conjugates; auristatin; calicheamicin; duocarmycin; Hodgkin's lymphoma; maytansine; multiple myeloma; NHL; non Hodgkin's lymphoma; ozogamicin

Indexed keywords

ANTINEOPLASTIC AGENT; AVE 9633; BLEOMYCIN; BORTEZOMIB; BR 96; BRENTUXIMAB VEDOTIN; CD33 ANTIGEN; CYCLOPHOSPHAMIDE; CYTARABINE; DACARBAZINE; DAUNORUBICIN; DEXAMETHASONE; DOXORUBICIN; DUOCARMYCIN DERIVATIVE; GEMTUZUMAB OZOGAMICIN; IMGN 901; IMMU 110; IMMUN 110; INOTUZUMAB OZOGAMICIN; LENALIDOMIDE; MDX 1206; MED 2460; NBT 062; PIBROZELESIN; PREDNISONE; RACHELMYCIN; RITUXIMAB; SAR 3419; SGN 35; SGN 75; UNCLASSIFIED DRUG; VINBLASTINE; VINCRISTINE SULFATE;

ACUTE GRANULOCYTIC LEUKEMIA; ACUTE KIDNEY FAILURE; ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION; AMINOTRANSFERASE BLOOD LEVEL; ANTIGEN EXPRESSION; ANTIMICROBIAL ACTIVITY; ANTINEOPLASTIC ACTIVITY; BLURRED VISION; BREAST CANCER; CANCER REGRESSION; CHRONIC LYMPHATIC LEUKEMIA; CLINICAL TRIAL; DIARRHEA; DRUG DOSE ESCALATION; DRUG FATALITY; DRUG FEVER; DRUG INDUCED HEADACHE; DRUG MEGADOSE; DRUG TOLERABILITY; DRUG WITHDRAWAL; EYE TOXICITY; FATIGUE; FEBRILE NEUTROPENIA; FOLLICULAR LYMPHOMA; GASTROINTESTINAL SYMPTOM; HEMATOLOGIC MALIGNANCY; HODGKIN DISEASE; HUMAN; HYPERBILIRUBINEMIA; HYPERGLYCEMIA; KERATITIS; KIDNEY CARCINOMA; LARGE CELL LYMPHOMA; LEUKOPENIA; LIVER TOXICITY; MELANOMA; METASTASIS; MULTIPLE CYCLE TREATMENT; MULTIPLE MYELOMA; NAUSEA; NEUROPATHY; NEUTROPENIA; NONHODGKIN LYMPHOMA; NONHUMAN; PERIPHERAL NEUROPATHY; PROSTATITIS; REVIEW; SIDE EFFECT; SKIN TOXICITY; SOLID TUMOR; THROMBOCYTOPENIA; TREATMENT DURATION; TREATMENT RESPONSE; VISUAL IMPAIRMENT; VOMITING;

ANIMALS; ANTIBODIES; ANTINEOPLASTIC AGENTS; CLINICAL TRIALS AS TOPIC; DRUG DELIVERY SYSTEMS; DRUG DESIGN; DRUG EVALUATION, PRECLINICAL; DRUGS, INVESTIGATIONAL; GENE EXPRESSION REGULATION, NEOPLASTIC; HEMATOLOGIC NEOPLASMS; HUMANS;

EID: 78650286160     PISSN: 13543784     EISSN: None     Source Type: Journal    
DOI: 10.1517/13543784.2011.539557     Document Type: Review

References (73)

1. Senter PD. Potent antibody drug conjugates for cancer therapy. Curr Opin Chem Biol 2009;13:235-44
2. Carter PJ, Senter PD. Antibody-drug conjugates for cancer therapy. Cancer J 2008;14:154-69
3. Polakis P. Arming antibodies for cancer therapy. Curr Opin Pharmacol 2005;5:382-7
4. Ducry L, Stump B. Antibody-drug conjugates: linking cytotoxic payloads to monoclonal antibodies. Bioconjug Chem 2010;21:5-13
5. Hamann PR, Hinman LM, Beyer CF, et al. An anti-CD33 antibody- calicheamicin conjugate for treatment of acute myeloid leukemia. Choice of linker. Bioconjug Chem 2002;13(1):40-6
6. Kovtun YV, Audette CA, Ye Y, et al. Antibody- drug conjugates designed to eradicate tumors with homogeneous and heterogeneous expression of the target antigen. Cancer Res 2006;66:3214-21
7. Sanderson RJ, Hering MA, James SF, et al. In vivo drug-linker stability of an anti-CD30 dipeptide-linked auristatin immunoconjugate. Clin Cancer Res 2005;11:843-52
8. Doronina SO, Mendelsohn BA, Bovee TD, et al. Enhanced activity of monomethylauristatin F through monoclonal antibody delivery: effects of linker technology on efficacy and toxicity. Bioconjug Chem 2006;17:114-24
9. Erickson HK, Park PU, Widdison WC, et al. Antibody- maytansinoid conjugates are activated in targeted cancer cells by lysosomal degradation and linker-dependent intracellular processing. Cancer Res 2006;66:4426-33
10. Garnett MC. Targeted drug conjugates: principles and progress. Adv Drug Deliv Rev 2001;53:171-216
11. Lambert JM. Drug-conjugated monoclonal antibodies for the treatment of cancer. Curr Opin Pharmacol 2005;5:543-9
12. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2009. CA Cancer J Clin 2009;59:225-49
13. Linenberger ML. CD33-directed therapy with gemtuzumab ozogamicin in acute myeloid leukemia: progress in understanding cytotoxicity and potential mechanisms of drug resistance. Leukemia 2005;19:176-82
14. Zein N, Poncin M, Nilakantan R, Ellestad GA. Calicheamicin gamma 1I and DNA: molecular recognition process responsible for site-specificity. Science 1989;244:697-9
15. Jedema I, Barge RMY, van der Velden VHJ, et al. Internalization and cell cycle-dependent killing of leukemic cells by Gemtuzumab Ozogamicin: rationale for efficacy in CD33-negative malignancies with endocytic capacity. Leukemia 2004;18:316-25
16. Shapiro M. Pfizer Prepares for Voluntary Withdrawal of U.S. New Drug Application and for Discontinuation of Commercial Availability of Mylotarg for Relapsed Acute Myeloid Leukemia. Ew York, NY: Pfizer, Inc., 2010. Available from: http://media.pfizer. com/files/products/mylotarg-hcp-letter. pdf [Last accessed 19 November 2010
17. Legrand O, Vidriales MB, Thomas X, et al. An open label, dose escalation study of AVE9633 administered as a single agent by intravenous (IV) infusion weekly for 2 weeks in 4-week cycle to patients with relapsed or refractory CD33-positive acute myeloid leukemia (AML). ASH Annual Meeting Abstracts 2007;110(11):1850
18. Connors JM. Evolving approaches to primary treatment of Hodgkin lymphoma. Hematology Am Soc Hematol Educ Program 2005:239-44
19. Pinter-Brown LC. SGN-30: a basis for the effective treatment of CD30 positive hematopoietic malignancies. Expert Opin Investig Drugs 2008;17(12):1883-7
20. Cerveny CG, Law C-L, McCormick RS, et al. Signaling via the anti-CD30 mAb SGN-30 sensitizes Hodgkin's disease cells to conventional chemotherapeutics. Leukemia 2005;19:1648-55
21. Younes A, Forero-Torres A, Bartlett NL, et al. Objective responses in a phase I dose-escalation study of SGN-35, a novel antibody-drug conjugate (ADC) targeting CD30, in patients with relapsed or refractory Hodgkin lymphoma. J Clin Oncol 2008;26(20 Suppl):abstract 8526
22. Fanale M, Bartlett NL, Forero-Torres A, et al. The antibody-drug conjugate brentuximab vedotin (SGN-35) induced multiple objective responses in patients with relapsed or refractory CD30-positive lymphomas in a phase 1 weekly dosing study. ASH Annual Meeting Abstracts 2009;114(22):2731
23. Bartlett NL, Grove LE, Kennedy DA, et al. Objective responses with brentuximab vedotin (SGN-35) retreatment in CD30-positive hematologic malignancies: a case series. J Clin Oncol 2010;28(15S):abstract 8062
24. Tse KF, Jeffers M, Pollack VA, et al. CR011, a fully human monoclonal antibody-auristatin E conjugate, for the treatment of melanoma. Clin Cancer Res 2006;12:1373-82
25. Burris H, Saleh M, Bendell J, et al. A phase (Ph) I/II study of CR011-VcMMAE, an antibody-drug conjugate, in patients (Pts) with locally advanced or metastatic breast cancer (MBC). Cancer Res 2009;69(24 Suppl):abstract nr 6096
26. Naumovski L, Junutula JR. Glembatumumab vedotin, a conjugate of an anti-glycoprotein non-metastatic melanoma protein B mAb and monomethyl auristatin E for the treatment of melanoma and breast cancer. Curr Opin Mol Ther 2010;12:248-57
27. Solal-Celigny P. Safety of rituximab maintenance therapy in follicular lymphomas. Leuk Res 2006;30(Suppl 1):S16-21
28. Billadeau DD, Leibson PJ. ITAMs versus ITIMs: striking a balance during cell regulation. J Clin Investig 2002;109:161-8
29. Tedder TF, Tuscano J, Sato S, Kehrl JH. CD22, a B lymphocyte-specific adhesion molecule that regulates antigen receptor signaling. Annu Rev Immunol 1997;15:481-504
30. DiJoseph JF, Goad ME, Dougher MM, et al. Potent and specific antitumor efficacy of CMC-544, a CD22-targeted immunoconjugate of calicheamicin, against systemically disseminated B-cell lymphoma. Clin Cancer Res 2004;10:8620-9
31. Dijoseph JF, Dougher MM, Kalyandrug LB, et al. Antitumor efficacy of a combination of CMC-544 (inotuzumab ozogamicin), a CD22-targeted cytotoxic immunoconjugate of calicheamicin, and rituximab against non-Hodgkin's B-cell lymphoma. Clin Cancer Res 2006;12:242-9
32. Dang N, Smith M, Offner F, et al. Anti-CD22 immunoconjugate inotuzumab ozogamicin (CMC-544) + rituximab: clinical activity including survival in patients with recurrent/refractory follicular or 'aggressive' lymphoma. ASH Annual Meeting Abstracts. Blood 2009;114(22):abstract 584
33. Fayad L, Patel H, Verhoef G, et al. Safety and clinical activity of the anti-CD22 immunoconjugate inotuzumab ozogamicin (CMC-544) in combination with rituximab in follicular lymphoma or diffuse large B-Cell lymphoma: preliminary report of a phase 1/2 study. ASH Annual Meeting Abstracts 2008;112(11):266
34. Ogura M, Tobinai K, Hatake K, et al. Phase I study of inotuzumab ozogamicin (CMC-544) in Japanese patients with follicular lymphoma pretreated with rituximab-based therapy. Cancer Sci 2010;101:1840-5
35. Rajvanshi P, Shulman HM, Sievers EL, McDonald GB. Hepatic sinusoidal obstruction after gemtuzumab ozogamicin (Mylotarg) therapy. Blood 2002;99:2310-14
36. Advani A, Coiffier B, Czuczman MS, et al. Safety, pharmacokinetics, and preliminary clinical activity of inotuzumab ozogamicin, a novel immunoconjugate for the treatment of B-cell non-Hodgkin's lymphoma: results of a phase I study. J Clin Oncol 2010;28:2085-93
37. Barclay AN, Brown M, Law SKA, et al. The leucocyte antigen facts book. Academic Press, San Diego, CA; 1997
38. Al-Katib AM, Aboukameel A, Mohammad R, et al. Superior antitumor activity of SAR3419 to rituximab in xenograft models for non-Hodgkin's lymphoma. Clin Cancer Res 2009;15:4038-45
39. Younes A, Gordon L, Kim S, et al. Phase I multi-dose escalation study of the anti-CD19 maytansinoid immunoconjugate SAR3419 administered by intravenous (IV) infusion every 3 weeks to patients with relapsed/refractory B-Cell non-hodgkin's lymphoma (NHL). ASH Annual Meeting Abstracts 2009;114(22):585
40. Gerber H-P, Kung-Sutherland M, Stone I, et al. Potent antitumor activity of the anti-CD19 auristatin antibody drug conjugate hBU12-vcMMAE against rituximab-sensitive and -resistant lymphomas. Blood 2009;113:4352-61
41. Alberts SR, Erlichman C, Reid JM, et al. Phase I study of the duocarmycin semisynthetic derivative KW-2189 given daily for five days every six weeks. Clin Cancer Res 1998;4:2111-17
42. Derwin D, Passmore D, Sung J, et al. Activation of antibody drug conjugate MDX-1203 by human carboxylesterase. Meeting of the American Association for Cancer Research 2010 [abstract 2575]. Available from: http://www. ibclifesciences.com/upload/wysiwyg/drug-discovery-series/D10201/ Passmore-Activation-of-Antibody.pdf [Last accessed 19 November 2010]
43. Rao C, Pan C, Vangipuram R, et al. Efficacy and toxicity of an anti-CD19 antibody drug conjugate. Annual Meeting of the American Association for Cancer Research; 2010; Washington, DC; 2010. p. 2452
44. Arens R, Schepers K, Nolte MA, et al. Tumor rejection induced by CD70-mediated quantitative and qualitative effects on effector CD8+ T cell formation. J Exp Med 2004;199:1595-605
45. Lens SM, Drillenburg P, den Drijver BF, et al. Aberrant expression and reverse signalling of CD70 on malignant B cells. Br J Haematol 1999;106:491-503
46. Oflazoglu E, Stone IJ, Gordon K, et al. Potent anticarcinoma activity of the humanized anti-CD70 antibody h1F6 conjugated to the tubulin inhibitor auristatin via an uncleavable linker. Clin Cancer Res 2008;14:6171-80
47. Wischhusen J, Jung G, Radovanovic I, et al. Identification of CD70-mediated apoptosis of immune effector cells as a novel immune escape pathway of human glioblastoma. Cancer Res 2002;62:2592-9
48. Alley SC, Benjamin DR, Jeffrey SC, et al. Contribution of linker stability to the activities of anticancer immunoconjugates. Bioconjug Chem 2008;19:759-65
49. Dijoseph JF, Dougher MM, Armellino DC, et al. CD20-specific antibody-targeted chemotherapy of non-Hodgkin's B-cell lymphoma using calicheamicin-conjugated rituximab. Cancer Immunol Immunother 2007;5:1107-17
50. Law C-L, Cerveny CG, Gordon KA, et al. Efficient elimination of B-lineage lymphomas by anti-CD20-auristatin conjugates. Clin Cancer Res 2004;10:7842-51
51. Polson AG, Calemine-Fenaux J, Chan P, et al. Antibody- drug conjugates for the treatment of non-Hodgkin's lymphoma: target and linker-drug selection. Cancer Res 2009;69:2358-64
52. Krop IE, Beeram M, Modi S, et al. Phase I study of trastuzumab-DM1, an HER2 antibody-drug conjugate, given every 3 weeks to patients with HER2-positive metastatic breast cancer. J Clin Oncol 2010;28:2698-704
53. Polson AG, Yu SF, Elkins K, et al. Antibody-drug conjugates targeted to CD79 for the treatment of non-Hodgkin's lymphoma. Blood 2007;110:616-23
54. Zheng B, Fuji RN, Elkins K, et al. In vivo effects of targeting CD79b with antibodies and antibody-drug conjugates. Mol Cancer Ther 2009;8:2937-46
55. Lin P, Owens R, Tricot G, Wilson CS. Flow cytometric immunophenotypic analysis of 306 cases of multiple myeloma. Am J Clin Pathol 2004;121:482-8
56. Tassone P, Gozzini A, Goldmacher V, et al. In vitro and in vivo activity of the maytansinoid immunoconjugate huN901-N2¢-deacetyl-N2¢-(3- mercapto-1-oxopropyl)-maytansine against CD56+ multiple myeloma cells. Cancer Res 2004;64:4629-36
57. Ikeda H, Hideshima T, Fulciniti M, et al. The monoclonal antibody nBT062 conjugated to cytotoxic maytansinoids has selective cytotoxicity against CD138 positive multiple myeloma cells in vitro and in vivo. Clin Cancer Res 2009;15:4028-37
58. Polson AG, Sliwkowski MX. Toward an effective targeted chemotherapy for multiple myeloma. Clin Cancer Res 2009;15:3906-7
59. Chanan-Khan AA, Jagannath S, Heffner LT, et al. Phase I study of BT062 given as repeated single dose once every 3 weeks in patients with relapsed or relapsed/refractory multiple myeloma. ASH Annual Meeting Abstracts 2009;114(22):1862
60. Chanan-Khan AA, Gharibo M, Jagannath S, et al. Phase I study of IMGN901 in patients with relapsed and relapsed/refractory CD56-positive multiple myeloma. ASH Annual Meeting Abstracts 2008;112(11):3689
61. Chanan-Khan A, Wolf J, Gharibo M, et al. Phase I study of IMGN901, used as monotherapy, in patients with heavily pre-treated CD56-positive multiple myeloma - a preliminary safety and efficacy analysis. ASH Annual Meeting Abstracts 2009;114(22):2883
62. Polson AG, Zheng B, Elkins K, et al. FcRL5 as a target of antibody-drug conjugates for the treatment of multiple myeloma. ASH Annual Meeting Abstracts 2009;114(22):3836
63. Sapra P, Stein R, Pickett J, et al. Anti-CD74 antibody-doxorubicin conjugate, IMMU-110, in a human multiple myeloma xenograft and in monkeys. Clin Cancer Res 2005;11:5257-64
64. Burton JD, Ely S, Reddy PK, et al. CD74 is expressed by multiple myeloma and is a promising target for therapy. Clin Cancer Res 2004;10:6606-11
65. Tijink BM, Buter J, de Bree R, et al. A Phase I dose escalation study with anti-CD44v6 bivatuzumab mertansine in patients with incurable squamous cell carcinoma of the head and neck or esophagus. Clin Cancer Res 2006;12:6064-72
66. Tolcher AW, Sugarman S, Gelmon KA, et al. Randomized phase II study of BR96-doxorubicin conjugate in patients with metastatic breast cancer. J Clin Oncol 1999;17:478-84
67. Dornan D, Bennett F, Chen Y, et al. Therapeutic potential of an anti-CD79b antibody-drug conjugate, anti-CD79b-vc-MMAE, for the treatment of non-Hodgkin lymphoma. Blood 2009;114:2721-9
68. Boghaert ER, Khandke K, Sridharan L, et al. Tumoricidal effect of calicheamicin immuno-conjugates using a passive targeting strategy. Int J Oncol 2006;28:675-84
69. Van Der Velden VHJ, Boeckx N, Jedema I, et al. High CD33-antigen loads in peripheral blood limit the efficacy of gemtuzumab ozogamicin (Mylotarg) treatment in acute myeloid leukemia patients. Leukemia 2004;18:983-8
70. Polson AG, Williams M, Gray AM, et al. Anti-CD22-MCC-DM1: an antibody-drug conjugate with a stable linker for the treatment of non-Hodgkin's lymphoma. Leukemia 2010;24:1566-73
71. Walter RB, Gooley TA, van der Velden VHJ, et al. CD33 expression and P-glycoprotein-mediated drug efflux inversely correlate and predict clinical outcome in patients with acute myeloid leukemia treated with gemtuzumab ozogamicin monotherapy. Blood 2007;109:4168-70
72. Walter RB, Raden BW, Hong TC, et al. Multidrug resistance protein attenuates gemtuzumab ozogamicin-induced cytotoxicity in acute myeloid leukemia cells. Blood 2003;102:1466-73
73. Tang R, Cohen S, Perrot J-Y, et al. P-gp activity is a critical resistance factor against AVE9633 and DM4 cytotoxicity in leukaemia cell lines, but not a major mechanism of chemoresistance in cells from acute myeloid leukaemia patients. BMC Cancer 2009;9:199