Effects of antibody, drug and linker on the preclinical and clinical toxicities of antibody-drug conjugates

mAbs

Volumn 8, Issue 4, 2016, Pages 659-671

  Donaghy, Heather ^a  

^a Hanson Wade   (United Kingdom)

Author keywords

ADC; Antibody drug conjugate; Clinical trials; Payload; Therapeutic index; Toxicity

Indexed keywords

3 (2 PYRIDYLDITHIO)PROPIONIC ACID N HYDROXYSUCCINIMIDE ESTER; ALDOXORUBICIN; ANTIBODY; ANTIBODY CONJUGATE; ANTINEOPLASTIC AGENT; BIVATUZUMAB MERTANSINE; BRENTUXIMAB VEDOTIN; CALICHEAMICIN; CANCER ANTIBODY; CANTUZUMAB MERTANSINE; CANTUZUMAB RAVTANSINE; CARBONIC ACID; CYTOTOXIC AGENT; DNA SYNTHESIS INHIBITOR; DNA TOPOISOMERASE INHIBITOR; DOXORUBICIN; DUOCARMYCIN DERIVATIVE; GLEMBATUMUMAB VEDOTIN; HYDRAZONE DERIVATIVE; INOTUZUMAB OZOGAMICIN; LINKER; MICROTUBULE INHIBITOR; N SUCCINIMIDYL 4 (2 PYRIDYLDITHIO) PENTANOATE; PINATUZUMAB VEDOTIN; POLATUZUMAB VEDOTIN; PYRROLOBENZODIAZEPINE; SUCCINIMIDYL 4 (N MALEIMIDOMETHYL) CYCLOHEXANE 1 CARBOXYLATE; UNCLASSIFIED DRUG; UNINDEXED DRUG; VEDOTIN; VORSETUZUMAB MAFODOTIN; MONOCLONAL ANTIBODY;

ANTIBODY DEPENDENT CELLULAR CYTOTOXICITY; CANCER THERAPY; CLINICAL TRIAL (TOPIC); COVALENT BOND; DISULFIDE BOND; DOSIMETRY; DRUG DESIGN; DRUG SCREENING; DRUG TARGETING; ENDOTHELIUM CELL; EYE TOXICITY; GASTROINTESTINAL TOXICITY; HUMAN; HYDROGEN BOND; HYPERGLYCEMIA; LIVER TOXICITY; LIVER VENOOCCLUSIVE DISEASE; MAXIMUM TOLERATED DOSE; NEUTROPENIA; NONHUMAN; PERIPHERAL NEUROPATHY; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SKIN TOXICITY; THERAPEUTIC INDEX; THROMBOCYTOPENIA; ANIMAL; NEOPLASM;

ANIMALS; ANTIBODIES, MONOCLONAL; ANTINEOPLASTIC AGENTS; HUMANS; IMMUNOCONJUGATES; NEOPLASMS;

EID: 84962366882     PISSN: 19420862     EISSN: 19420870     Source Type: Journal    
DOI: 10.1080/19420862.2016.1156829     Document Type: Review

References (98)

1. R.J.Williams, T.Tse, K.DiPiazza, D.A.Zarin. Terminated trials in the ClinicalTrials.gov results database: Evaluation of availability of primary outcome data and reasons for termination. PLoS One 2015; 10:e0127242; PMID:26011295; http://dx.doi.org/10.1371/journal.pone.0127242
2. E.L.Sievers, P.D.Senter. Antibody-drug conjugates in cancer therapy. Annu Rev Med 2013; 64:15-29; PMID:23043493; http://dx.doi.org/10.1146/annurev-med-050311-201823
3. N.Jain, S.W.Smith, S.Ghone, B.Tomczuk. Current ADC linker chemistry. Pharm Res 2015; 32(11):3526-40; http://dx.doi.org/10.1007/s11095-015-1657-7
4. T.M.Cardillo, S.V.Govindan, R.M.Sharkey, P.Trisal, D.M.Goldenberg. Humanized anti-trop-2 IgG-SN-38 conjugate for effective treatment of diverse epithelial cancers: Preclinical studies in human cancer xenograft models and monkeys. Clin Cancer Res 2011; 17:3157-69; PMID:21372224; http://dx.doi.org/10.1158/1078-0432.CCR-10-2939
5. S.V.Govindan, T.M.Cardillo, S.J.Moon, H.J.Hansen, D.M.Goldenberg. CEACAM5-targeted therapy of human colonic and pancreatic cancer xenografts with potent labetuzumab-SN-38 immunoconjugates. Clin Cancer Res 2009; 15:6052-61; PMID:19789330; http://dx.doi.org/10.1158/1078-0432.CCR-09-0586
6. B.M.Tijink, J.Buter, R.de Bree, G.Giaccone, M.S.Lang, A.Staab, C.R.Leemans, G.A.van Dongen. 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; PMID:17062682
7. C.M.Annunziata, E.C.Kohn, P.LoRusso, N.D.Houston, R.L.Coleman, M.Buzoianu, G.Robbie, R.Lechleider. Phase 1, open-label study of MEDI-547 in patients with relapsed or refractory solid tumors. Invest New Drugs 2013; 31:77-84; PMID:22370972; http://dx.doi.org/10.1007/s10637-012-9801-2
8. A.W.Tolcher, S.Sugarman, K.A.Gelmon, R.Cohen, M.Saleh, C.Isaacs, L.Young, D.Healey, N.Onetto, W.Slichenmyer. Randomized phase II study of BR96-doxorubicin conjugate in patients with metastatic breast cancer. J Clin Oncol 1999; 17:478-84; PMID:10080588
9. S.Panowksi, S.Bhakta, H.Raab, P.Polakis, J.R.Junutula. Site-specific antibody drug conjugates for cancer therapy. MAbs 2014; 6:34-45; PMID:24423619; http://dx.doi.org/10.4161/mabs.27022
10. B.Gorovits, C.Krinos-Fiorotti. Proposed mechanism of off-target toxicity for antibody-drug conjugates driven by mannose receptor uptake. Cancer Immunol Immunother 2013; 62:217-23; PMID:23223907; http://dx.doi.org/10.1007/s00262-012-1369-3
11. E.Komlodi-Pasztor, D.Sackett, J.Wilkerson, T.Fojo. Mitosis is not a key target of microtubule agents in patient tumors. Nat Rev Clin Oncol 2011; 8:244-50; PMID:21283127; http://dx.doi.org/10.1038/nrclinonc.2010.228
12. P.R.Hamann, L.M.Hinman, I.Hollander, C.F.Beyer, D.Lindh, R.Holcomb, W.Hallett, H.R.Tsou, J.Upeslacis, D.Shochat, et al. Gemtuzumab ozogamicin, a potent and selective anti-CD33 antibody-calicheamicin conjugate for treatment of acute myeloid leukemia. Bioconjug Chem 2002; 13:47-58; PMID:11792178
13. P.D.Senter. Potent antibody drug conjugates for cancer therapy. Curr Opin Chem Biol 2009; 13:235-44; PMID:19414278; http://dx.doi.org/10.1016/j.cbpa.2009.03.023
14. K.J.Hamblett, P.D.Senter, D.F.Chace, M.M.Sun, J.Lenox, C.G.Cerveny, K.M.Kissler, S.X.Bernhardt, A.K.Kopcha, R.F.Zabinski, et al. Effects of drug loading on the antitumor activity of a monoclonal antibody drug conjugate. Clin Cancer Res 2004; 10:7063-70; PMID:15501986
15. J.R.Junutula, H.Raab, S.Clark, S.Bhakta, D.D.Leipold, S.Weir, Y.Chen, M.Simpson, S.P.Tsai, M.S.Dennis, et al. Site-specific conjugation of a cytotoxic drug to an antibody improves the therapeutic index. Nat Biotechnol 2008; 26:925-32; PMID:18641636; http://dx.doi.org/10.1038/nbt.1480
16. H.Uppal, E.Doudement, K.Mahapatra, W.C.Darbonne, D.Bumbaca, B.Q.Shen, X.Du, O.Saad, K.Bowles, S.Olsen, et al. Potential mechanisms for thrombocytopenia development with trastuzumab emtansine (T-DM1). Clin Cancer Res 2015; 21:123-33; PMID:25370470; http://dx.doi.org/10.1158/1078-0432.CCR-14-2093
17. J.N.Thon, M.T.Devine, B.JurakBegonja.A, J.Tibbitts, J.E.Italiano, Jr. High-content live-cell imaging assay used to establish mechanism of trastuzumab emtansine (T-DM1)–mediated inhibition of platelet production. Blood 2012; 120:1975-84; PMID:22665936; http://dx.doi.org/10.1182/blood-2012-04-420968
18. A.Zeuner, M.Signore, D.Martinetti, M.Bartucci, C.Peschle, R.De Maria. Chemotherapy-induced thrombocytopenia derives from the selective death of megakaryocyte progenitors and can be rescued by stem cell factor. Cancer Res 2007; 67:4767-73; PMID:17510405
19. J.A.Thompson, R.Motzer, A.M.Molina, T.K.Choueiri, E.I.Heath, C.K.Kollmannsberger, B.G.Redman, R.S.Sangha, D.S.Ernst, R.Pili, et al. Phase I studies of anti-ENPP3 antibody drug conjugates (ADCs) in advanced refractory renal cell carcinomas (RRCC). ASCO Meeting Abstracts 2015; 33:2503
20. N.M.Tannir, A.Forero-Torres, R.Ramchandren, S.K.Pal, S.M.Ansell, J.R.Infante, S.de Vos, P.A.Hamlin, S.K.Kim, N.C.Whiting, et al. Phase I dose-escalation study of SGN-75 in patients with CD70-positive relapsed/refractory non-hodgkin lymphoma or metastatic renal cell carcinoma. Invest New Drugs 2014; 32:1246-57; PMID:25142258; http://dx.doi.org/10.1007/s10637-014-0151-0
21. H.K.Gan, K.P.Papadopoulos, L.Fichtel, A.B.Lassman, R.Merrell, M.J.Van Den Bent, P.Kumthekar, A.M.Scott, M.Pedersen, E.J.Gomez, et al. Phase I study of ABT-414 mono- or combination therapy with temozolomide (TMZ) in recurrent glioblastoma (GBM). ASCO Meeting Abstracts 2015; 33:2016
22. C.H.Moskowitz, A.Forero-Torres, B.D.Shah, R.Advani, P.Hamlin, S.Kim, A.Kostic, L.Sandalic, B.Zhao, M.A.Fanale. Interim analysis of a phase 1 study of the antibody-drug conjugate SGN-CD19A in relapsed or refractory B-lineage non-hodgkin lymphoma. Blood 2014; 124:1741
23. C.H.Moskowitz, M.A.Fanale, B.D.Shah, R.H.Advani, R.Chen, S.Kim, A.Kostic, T.Liu, J.Peng, A.Forero-Torres. A phase 1 study of denintuzumab mafodotin (SGN-CD19A) in Relapsed/Refactory B-lineage non-hodgkin lymphoma. Blood 2015; 126:182
24. A.T.Fathi, U.Borate, D.J.DeAngelo, M.M.O'Brien, T.Trippett, B.D.Shah, G.A.Hale, J.M.Foran, L.B.Silverman, R.Tibes, et al. A phase 1 study of denintuzumab mafodotin (SGN-CD19A) in adults with relapsed or refractory B-lineage acute leukemia (B-ALL) and highly aggressive lymphoma. Blood 2015; 126:1328
25. A.Advani, B.Coiffier, M.S.Czuczman, M.Dreyling, J.Foran, E.Gine, C.Gisselbrecht, N.Ketterer, S.Nasta, A.Rohatiner, 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; PMID:20308665; http://dx.doi.org/10.1200/JCO.2009.25.1900
26. E.L.Sievers, R.A.Larson, E.A.Stadtmauer, E.Estey, B.Lowenberg, H.Dombret, C.Karanes, M.Theobald, J.M.Bennett, M.L.Sherman, et al. Efficacy and safety of gemtuzumab ozogamicin in patients with CD33-positive acute myeloid leukemia in first relapse. J Clin Oncol 2001; 19:3244-54; PMID:11432892
27. D.S.Hong, I.Garrido-Laguna, I.E.Krop, V.Subbiah, T.L.Werner, C.M.Cotter, E.P.Hamilton, K.Velastegui, D.Xuan, R.Bugarini, et al. First-in-human dose escalation, safety, and PK study of a novel EFNA4-ADC in patients with advanced solid tumors. ASCO Meeting Abstracts 2015; 33:2520
28. V.Dieras, N.Harbeck, G.T.Budd, J.K.Greenson, A.E.Guardino, M.Samant, N.Chernyukhin, M.C.Smitt, I.E.Krop. Trastuzumab emtansine in human epidermal growth factor receptor 2-positive metastatic breast cancer: An integrated safety analysis. J Clin Oncol 2014; 32:2750-7; PMID:25024070; http://dx.doi.org/10.1200/JCO.2013.54.4999
29. E.L.Sievers, F.R.Appelbaum, R.T.Spielberger, S.J.Forman, D.Flowers, F.O.Smith, K.Shannon-Dorcy, M.S.Berger, I.D.Bernstein. Selective ablation of acute myeloid leukemia using antibody-targeted chemotherapy: A phase I study of an anti-CD33 calicheamicin immunoconjugate. Blood 1999; 93:3678-84; PMID:10339474
30. S.Lapusan, M.B.Vidriales, X.Thomas, S.de Botton, A.Vekhoff, R.Tang, C.Dumontet, R.Morariu-Zamfir, J.M.Lambert, M.L.Ozoux, et al. Phase I studies of AVE9633, an anti-CD33 antibody-maytansinoid conjugate, in adult patients with relapsed/refractory acute myeloid leukemia. Invest New Drugs 2012; 30:1121-31; PMID:21519855; http://dx.doi.org/10.1007/s10637-011-9670-0
31. J.S.Eaton, P.E.Miller, M.J.Mannis, C.J.Murphy. Ocular adverse events associated with antibody-drug conjugates in human clinical trials. J Ocul Pharmacol Ther 2015; 31:589-604; PMID:26539624; http://dx.doi.org/10.1089/jop.2015.0064
32. M.M.Mita, A.D.Ricart, A.C.Mita, A.Patnaik, J.Sarantopoulos, K.Sankhala, R.J.Fram, A.Qin, J.Watermill, A.W.Tolcher. A phase I study of a CanAg-targeted immunoconjugate, huC242-DM4, in patients with can ag-expressing solid tumors. 2007; 25:2062
33. H.Borghaei, D.M.O'Malley, S.M.Seward, T.M.Bauer, R.P.Perez, A.M.Oza, W.Jeong, M.F.Michenzie, M.W.Kirby, G.Chandorkar, et al. Phase 1 study of IMGN853, a folate receptor alpha (FR{alpha})-targeting antibody-drug conjugate (ADC) in patients (pts) with epithelial ovarian cancer (EOC) and other FRA-positive solid tumors. ASCO Meeting Abstracts 2015; 33:5558
34. A.Younes, S.Kim, J.Romaguera, A.Copeland, S.FarialSdC, L.W.Kwak, L.Fayad, F.Hagemeister, M.Fanale, S.Neelapu, et al. Phase I multidose-escalation study of the anti-CD19 maytansinoid immunoconjugate SAR3419 administered by intravenous infusion every 3 weeks to patients with Relapsed/Refractory B-cell lymphoma. J Clin Oncol 2012; 30(22):2776-82; http://dx.doi.org/10.1200/JCO.2011.39.4403
35. D.J.Renouf, J.P.Velazquez-Martin, R.Simpson, L.L.Siu, P.L.Bedard. Ocular toxicity of targeted therapies. J Clin Oncol 2012; 30:3277-86; PMID:22649132; http://dx.doi.org/10.1200/JCO.2011.41.5851
36. J.M.Cleary, D.A.Reardon, N.Azad, L.Gandhi, G.I.Shapiro, J.Chaves, M.Pedersen, P.Ansell, W.Ames, H.Xiong, et al. A phase 1 study of ABT-806 in subjects with advanced solid tumors. Invest New Drugs 2015; 33:671-8; PMID:25895099; http://dx.doi.org/10.1007/s10637-015-0234-6
37. K.J.Hamblett, C.J.Kozlosky, S.Siu, W.S.Chang, H.Liu, I.N.Foltz, E.S.Trueblood, D.Meininger, T.Arora, B.Twomey, et al. AMG 595, an anti-EGFRvIII antibody-drug conjugate, induces potent antitumor activity against EGFRvIII-expressing glioblastoma. Mol Cancer Ther 2015; 14(7):1614-24; PMID:25931519
38. A.Younes, N.L.Bartlett, J.P.Leonard, D.A.Kennedy, C.M.Lynch, E.L.Sievers, A.Forero-Torres. Brentuximab vedotin (SGN-35) for relapsed CD30-positive lymphomas. N Engl J Med 2010; 363:1812-21; PMID:21047225; http://dx.doi.org/10.1056/NEJMoa1002965
39. C.Vaklavas, A.Forero-Torres. Safety and efficacy of brentuximab vedotin in patients with hodgkin lymphoma or systemic anaplastic large cell lymphoma. Ther Adv Hematol 2012; 3:209-25; PMID:23606932; http://dx.doi.org/10.1177/2040620712443076
40. G.SeattleGenetics. Adcetris (brentuximab vedotin) prescribing information. 2015.
41. M.C.Palanca-Wessels, M.Czuczman, G.Salles, S.Assouline, L.H.Sehn, I.Flinn, M.R.Patel, R.Sangha, A.Hagenbeek, R.Advani, et al. Safety and activity of the anti-CD79B antibody-drug conjugate polatuzumab vedotin in relapsed or refractory B-cell non-hodgkin lymphoma and chronic lymphocytic leukaemia: A phase 1 study. Lancet Oncol 2015; 16:704-15; PMID:25925619; http://dx.doi.org/10.1016/S1470-2045(15)70128-2
42. D.A.Yardley, R.Weaver, M.E.Melisko, M.N.Saleh, F.P.Arena, A.Forero, T.Cigler, A.Stopeck, D.Citrin, I.Oliff, et al. EMERGE: A randomized phase II study of the antibody-drug conjugate glembatumumab vedotin in advanced glycoprotein NMB-expressing breast cancer. J Clin Oncol 2015; 33:1609-19; PMID:25847941; http://dx.doi.org/10.1200/JCO.2014.56.2959
43. A.Younes, A.K.Gopal, S.E.Smith, S.M.Ansell, J.D.Rosenblatt, K.J.Savage, R.Ramchandren, N.L.Bartlett, B.D.Cheson, S.de Vos, et al. Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory hodgkin's lymphoma. J Clin Oncol 2012; 30:2183-9; PMID:22454421; http://dx.doi.org/10.1200/JCO.2011.38.0410
44. A.Sauter, C.Kloft, S.Gronau, F.Bogeschdorfer, T.Erhardt, W.Golze, C.Schroen, A.Staab, H.Riechelmann, K.Hoermann. Pharmacokinetics, immunogenicity and safety of bivatuzumab mertansine, a novel CD44v6-targeting immunoconjugate, in patients with squamous cell carcinoma of the head and neck. Int J Oncol 2007; 30:927-35; PMID:17332932; http://dx.doi.org/10.3892/ijo.30.4.927
45. H.Riechelmann, A.Sauter, W.Golze, G.Hanft, C.Schroen, K.Hoermann, T.Erhardt, S.Gronau. Phase I trial with the CD44v6-targeting immunoconjugate bivatuzumab mertansine in head and neck squamous cell carcinoma. Oral Oncol 2008; 44:823-9; PMID:18203652; http://dx.doi.org/10.1016/j.oraloncology.2007.10.009
46. U.Rupp, E.Schoendorf-Holland, M.Eichbaum, F.Schuetz, I.Lauschner, P.Schmidt, A.Staab, G.Hanft, J.Huober, H.P.Sinn, et al. Safety and pharmacokinetics of bivatuzumab mertansine in patients with CD44v6-positive metastatic breast cancer: Final results of a phase I study. Anticancer Drugs 2007; 18:477-85; PMID:17351401; http://dx.doi.org/10.1097/CAD.0b013e32801403f4
47. J.W.Lee, H.D.Han, M.M.Shahzad, S.W.Kim, L.S.Mangala, A.M.Nick, C.Lu, R.R.Langley, R.Schmandt, H.S.Kim, et al. EphA2 immunoconjugate as molecularly targeted chemotherapy for ovarian carcinoma. J Natl Cancer Inst 2009; 101:1193-205; PMID:19641174; http://dx.doi.org/10.1093/jnci/djp231
48. H.Inrhaoun, T.Kullmann, I.Elghissassi, H.Mrabti, H.Errihani. Treatment of chemotherapy-induced nausea and vomiting. J Gastrointest Cancer 2012; 43:541-6; PMID:22733566; http://dx.doi.org/10.1007/s12029-012-9401-6
49. N.Bouganim, G.Dranitsaris, S.Hopkins, L.Vandermeer, L.Godbout, S.Dent, P.Wheatley-Price, C.Milano, M.Clemons. Prospective validation of risk prediction indexes for acute and delayed chemotherapy-induced nausea and vomiting. Curr Oncol 2012; 19:e414-21; PMID:23300365; http://dx.doi.org/10.3747/co.19.1074
50. R.J.Gibson, D.M.Keefe. Cancer chemotherapy-induced diarrhoea and constipation: Mechanisms of damage and prevention strategies. Support Care Cancer 2006; 14:890-900; PMID:16604351; http://dx.doi.org/10.1007/s00520-006-0040-y
51. D.J.DeAngelo, M.Stelljes, G.Martinelli, H.Kantarjian, M.Liedtke, W.Stock, N.Goekbuget, K.Wang, L.Pacagnella, B.Sleight, et al. Efficacy and safety of inotuzumab ozogamicin (INO) vs standard of care (SOC) in salvage 1 or 2 patients with acute lymphoblastic leukemia (ALL): An ongoing global phase 3 study. 2015.
52. J.M.McKoy, C.Angelotta, C.L.Bennett, M.S.Tallman, M.Wadleigh, A.M.Evens, T.M.Kuzel, S.M.Trifilio, D.W.Raisch, J.Kell, et al. Gemtuzumab ozogamicin-associated sinusoidal obstructive syndrome (SOS): An overview from the research on adverse drug events and reports (RADAR) project. Leuk Res 2007; 31:599-604; PMID:16959316
53. C.Nabhan, L.Rundhaugen, M.Jatoi, M.B.Riley, L.Boehlke, L.C.Peterson, M.S.Tallman. Gemtuzumab ozogamicin (MylotargTM) is infrequently associated with sinusoidal obstructive syndrome/veno-occlusive disease. Ann Oncol 2004; 15:1231-6; PMID:15277263; http://dx.doi.org/10.1093/annonc/mdh324
54. A.W.Tolcher, L.Ochoa, L.A.Hammond, A.Patnaik, T.Edwards, C.Takimoto, L.Smith, J.de Bono, G.Schwartz, T.Mays, et al. Cantuzumab mertansine, a maytansinoid immunoconjugate directed to the CanAg antigen: A phase I, pharmacokinetic, and biologic correlative study. J Clin Oncol 2003; 21:211-22; PMID: 12525512; http://dx/doi.org/10.1200/JCO.2003.05.137
55. K.A.Poon, K.Flagella, J.Beyer, J.Tibbitts, S.Kaur, O.Saad, J.H.Yi, S.Girish, N.Dybdal, T.Reynolds. Preclinical safety profile of trastuzumab emtansine (T-DM1): Mechanism of action of its cytotoxic component retained with improved tolerability. Toxicol Appl Pharmacol 2013; 273:298-313; PMID:24035823; http://dx.doi.org/10.1016/j.taap.2013.09.003
56. N.H.Dang, M.Ogura, S.Castaigne, L.Fayad, M.Jerkeman, J.A.Radford, A.Pezzutto, I.Bondarenko, D.A.Stewart, M.Shnaidman, et al. Randomized, phase 3 trial of inotuzumab ozogamicin plus rituximab (R-InO) versus chemotherapy for relapsed/refractory aggressive B-cell non-hodgkin lymphoma (B-NHL). ASCO Meeting Abstracts 2014; 32:8529
57. A.Younes, J.M.Connors, S.I.Park, M.Fanale, M.M.O'Meara, N.N.Hunder, D.Huebner, S.M.Ansell. Brentuximab vedotin combined with ABVD or AVD for patients with newly diagnosed hodgkin's lymphoma: A phase 1, open-label, dose-escalation study. Lancet Oncol 2013; 14:1348-56; PMID:24239220; http://dx.doi.org/10.1016/S1470-2045(13)70501-1
58. S.Bristol-MyersSquibb. Blenoxane (bleomycin sulfate), prescribing information. 1999.
59. NCT01712490. Phase 3 frontline therapy trial in patients with advanced classical hodgkin lymphoma.
60. Pfizer. CAMPTOSAR (irinotecan hydrochloride) prescribing information. 2014.
61. E.Dotan, A.Starodub, J.Berlin, C.H.Lieu, M.J.Guarino, J.Marshall, J.R.Hecht, S.J.Cohen, W.A.Messersmith, P.P.Maliakal, et al. A new anti-CEA-SN-38 antibody-drug conjugate (ADC), IMMU-130, is active in controlling metastatic colorectal cancer (mCRC) in patients (pts) refractory or relapsing after irinotecan-containing chemotherapies: Initial results of a phase I/II study. ASCO Meeting Abstracts 2015; 33:2505
62. K.N.Moore, J.Ponte, P.LoRusso, M.J.Birrer, T.M.Bauer, H.Borghaei, D.M.O'Malley, R.Ruiz-Soto, R.Lutz, L.Malik. Relationship of pharmacokinetics (PK), toxicity, and initial evidence of clinical activity with IMGN853, a folate receptor alpha (FRa) targeting antibody drug conjugate in patients (pts) with epithelial ovarian cancer (EOC) and other FRa-positive solid tumors. ASCO Meeting Abstracts 2014; 32:5571
63. K.N.Moore, L.P.Martin, S.M.Seward, T.M.Bauer, D.M.O'Malley, R.P.Perez, A.M.Oza, W.Jeong, M.W.Kirby, Y.Zhou, et al. Preliminary single agent activity of IMGN853, a folate receptor alpha (FR{alpha})-targeting antibody-drug conjugate (ADC), in platinum-resistant epithelial ovarian cancer (EOC) patients (pts): Phase I trial. ASCO Meeting Abstracts 2015; 33:5518
64. V.Ribrag, J.Dupuis, H.Tilly, F.Morschhauser, F.Laine, R.Houot, C.Haioun, C.Copie, A.Varga, J.Lambert, et al. A dose-escalation study of SAR3419, an anti-CD19 antibody maytansinoid conjugate, administered by intravenous infusion once weekly in patients with relapsed/refractory B-cell non-hodgkin lymphoma. Clin Cancer Res 2014; 20:213-20; PMID:24132920; http://dx.doi.org/10.1158/1078-0432.CCR-13-0580
65. S.Castaigne, C.Pautas, C.Terre, E.Raffoux, D.Bordessoule, J.N.Bastie, O.Legrand, X.Thomas, P.Turlure, O.Reman, et al. Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia (ALFA-0701): A randomised, open-label, phase 3 study. Lancet 2012; 379:1508-16; http://dx.doi.org/10.1016/S0140-6736(12)60485-1
66. P.Sapra, A.Betts, J.Boni. Preclinical and clinical pharmacokinetic/pharmacodynamic considerations for antibody-drug conjugates. Expert Rev Clin Pharmacol 2013; 6:541-55; PMID:23978126; http://dx.doi.org/10.1586/17512433.2013.827405
67. F.Donate, A.Raitano, K.Morrison, Z.An, L.Capo, H.Avina, S.Karki, K.Morrison, P.Yang, J.Ou, et al. AGS16F is a novel antibody drug conjugate directed against ENPP3 for the treatment of renal cell carcinoma. Clin Cancer Res 2015;
68. P.Hossler, S.F.Khattak, Z.J.Li. Optimal and consistent protein glycosylation in mammalian cell culture. Glycobiology 2009; 19:936-49; PMID:19494347; http://dx.doi.org/10.1093/glycob/cwp079
69. P.A.Ott, O.Hamid, A.C.Pavlick, H.Kluger, K.B.Kim, P.D.Boasberg, R.Simantov, E.Crowley, J.A.Green, T.Hawthorne, et al. Phase I/II study of the antibody-drug conjugate glembatumumab vedotin in patients with advanced melanoma. J Clin Oncol 2014; 32:3659-66; PMID:25267741; http://dx.doi.org/10.1200/JCO.2013.54.8115
70. A.Bardia, L.T.Vahdat, J.R.Diamond, A.Starodub, R.L.Moroose, S.J.Isakoff, A.J.Ocean, J.Berlin, W.A.Messersmith, S.S.Thomas, et al. Therapy of refractory/relapsed metastatic triple-negative breast cancer (TNBC) with an anti-trop-2-SN-38 antibody-drug conjugate (ADC), sacituzumab govitecan (IMMU-132): Phase I/II clinical experience. ASCO Meeting Abstracts 2015; 33:1016
71. M.J.Guarino, A.Starodub, G.A.Masters, R.S.Heist, W.A.Messersmith, A.Bardia, A.J.Ocean, S.S.Thomas, P.P.Maliakal, W.A.Wegener, et al. Therapy of advanced metastatic lung cancer with an anti-trop-2-SN-38 antibody-drug conjugate (ADC), sacituzumab govitecan (IMMU-132): Phase I/IIclinical experience. ASCO Meeting Abstracts 2015; 33:2504
72. A.Starodub, A.J.Ocean, W.A.Messersmith, V.J.Picozzi, M.J.Guarino, A.Bardia, S.S.Thomas, J.Berlin, M.A.Shah, P.P.Maliakal, et al. Therapy of gastrointestinal malignancies with an anti-trop-2-SN-38 antibody drug conjugate (ADC) (sacituzumab govitecan): Phase I/IIclinical experience. ASCO Meeting Abstracts 2015; 33:3546
73. P.Strop, K.Delaria, D.Foletti, J.M.Witt, A.Hasa-Moreno, K.Poulsen, M.G.Casas, M.Dorywalska, S.Farias, A.Pios, et al. Site-specific conjugation improves therapeutic index of antibody drug conjugates with high drug loading. Nat Biotechnol 2015; 33:694-6; PMID:26154005; http://dx.doi.org/10.1038/nbt.3274
74. R.P.Lyon, T.D.Bovee, S.O.Doronina, P.J.Burke, J.H.Hunter, H.D.Neff-LaFord, M.Jonas, M.E.Anderson, J.R.Setter, P.D.Senter. Reducing hydrophobicity of homogeneous antibody-drug conjugates improves pharmacokinetics and therapeutic index. Nat Biotechnol 2015; 33:733-5; PMID:26076429; http://dx.doi.org/10.1038/nbt.3212
75. F.Lhospice, D.Bregeon, C.Belmant, P.Dennler, A.Chiotellis, E.Fischer, L.Gauthier, A.Boedec, H.Rispaud, S.Savard-Chambard, et al. Site-specific conjugation of monomethyl auristatin E to anti-CD30 antibodies improves their pharmacokinetics and therapeutic index in rodent models. Mol Pharm 2015; 12:1863-71; PMID:25625323
76. D.A.Kennedy, S.C.Alley, B.Zhao, E.J.Feldman, M.O'Meara, M.Sutherland. SGN-CD33A: Preclinical and phase 1 interim clinical trial results of a CD33-directed PBD dimer antibody-drug conjugate for the treatment of acute myeloid leukemia (AML). 2015:DDT02-04.
77. Bayer Health Care. Clinical study report no. PH-37705. 2014.
78. A.L.Coveler, D.D.Von Hoff, A.H.Ko, N.C.Whiting, B.Zhao, B.M.Wolpin. A phase I study of ASG-5ME, a novel antibody-drug conjugate, in pancreatic ductal adenocarcinoma. ASCO Meeting Abstracts 2013; 31:176
79. J.Bendell, M.Saleh, A.A.N.Rose, P.M.Siegel, L.Hart, S.Sirpal, S.Jones, J.Green, E.Crowley, R.Simantov, et al. Phase I/II study of the antibody-drug conjugate glembatumumab vedotin in patients with locally advanced or metastatic breast cancer. J Clin Oncol 2014; 32:3619-25; PMID:25267761; http://dx.doi.org/10.1200/JCO.2013.52.5683
80. C.Cruz Zambrano, K.Almhanna, W.A.Messersmith, J.Rodon Ahnert, D.P.Ryan, J.E.Faris, J.Jung, A.Fasanmade, T.Wyant, T.Kalebic. MLN0264, an investigational antiguanylyl cyclase C (GCC) antibody-drug conjugate (ADC), in patients (pts) with advanced gastrointestinal (GI) malignancies: Phase I study. ASCO Meeting Abstracts 2014; 32:3546
81. D.P.Petrylak, P.W.Kantoff, A.E.Mega, N.J.Vogelzang, J.Stephenson, M.T.Fleming, N.Stambler, M.Petrini, S.Blattman, R.J.Israel. Prostate-specific membrane antigen antibody drug conjugate (PSMA ADC): A phase I trial in metastatic castration-resistant prostate cancer (mCRPC) previously treated with a taxane. ASCO Meeting Abstracts 2013; 31:5018
82. D.P.Petrylak, N.J.Vogelzang, G.S.Chatta, M.T.Fleming, D.C.Smith, L.J.Appleman, A.Hussain, M.Modiano, P.Singh, S.T.Tagawa, et al. A phase 2 study of prostate specific membrane antigen antibody drug conjugate (PSMA ADC) in patients (pts) with progressive metastatic castration-resistant prostate cancer (mCRPC) following abiraterone and/or enzalutamide (abi/enz). ASCO Meeting Abstracts 33:144
83. A.I.Chen, D.Lebovic, M.W.Brunvand, A.Goy, J.E.Chang, E.Hochberg, S.Yalamanchili, R.Kahn, D.Lu, A.Chai, et al. Final results of a phase I study of the anti-CD22 antibody-drug conjugate (ADC) DCDT2980S with or without rituximab (RTX) in patients (pts) with relapsed or refractory (R/R) B-cell non-Hodgkin/textquoterights lymphoma (NHL). Blood 2013; 122:4399
84. R.Advani, D.Lebovic, M.Brunvand, A.I.Chen, A.Goy, J.E.Chang, L.S.Maeda, W.Ho, R.Kahn, D.Lu, et al. A phase I study of DCDT2980S, an antibody-drug conjugate (ADC) targeting CD22, in relapsed or refractory B-cell non-hodgkin's lymphoma (NHL). Blood 2015; 120:59
85. J.R.Infante, S.K.Sandhu, C.M.McNeil, O.Kabbarah, C.Li, W.Zhong, J.Asundi, K.Wood, Y.Chu, O.Hamid. Abstract CT233: A first-in-human phase I study of the safety and pharmacokinetic (PK) activity of DEDN6526A, an anti-endothelin B receptor (ETBR) antibody-drug conjugate (ADC), in patients with metastatic or unresectable melanoma. Cancer Res 2014; 74:CT233; http://dx.doi.org/10.1158/1538-7445.AM2014-CT233
86. C.D.Weekes, L.E.Lamberts, M.J.Borad, J.Voortman, R.R.McWilliams, J.R.Diamond, E.De Vries, H.M.W.Verheul, C.H.Lieu, H.Yue, et al. A phase I study of DMOT4039A, an antibody-drug conjugate (ADC) targeting mesothelin (MSLN), in patients (pts) with unresectable pancreatic (PC) or platinum-resistant ovarian cancer (OC). ASCO Meeting Abstracts 2014; 32:2529
87. J.Liu, K.Moore, M.Birrer, S.Berlin, U.Matulonis, J.Infante, J.Xi, R.Kahn, Y.Wang, K.Wood, et al. Abstract LB-290: Targeting MUC16 with the antibody-drug conjugate (ADC) DMUC5754A in patients with platinum-resistant ovarian cancer: A phase I study of safety and pharmacokinetics. Cancer Res 2013; 73:LB-290
88. I.Genentech. Kadcyla prescribing information. 2015.
89. M.D.Galsky, M.Eisenberger, S.Moore-Cooper, W.K.Kelly, S.F.Slovin, A.DeLaCruz, Y.Lee, I.J.Webb, H.I.Scher. Phase I trial of the prostate-specific membrane antigen-directed immunoconjugate MLN2704 in patients with progressive metastatic castration-resistant prostate cancer. J Clin Oncol 2008; 26:2147-54; PMID:18362364; http://dx.doi.org/10.1158/1078-0432.CCR-15-1542
90. J.G.Berdeja. Lorvotuzumab mertansine: Antibody-drug-conjugate for CD56+ multiple myeloma. Front Biosci (Landmark Ed) 2014; 19:163-70; PMID:24389179
91. D.S.Thompson, A.Patnaik, J.C.Bendell, K.Papadopoulos, J.R.Infante, R.A.Mastico, D.Johnson, A.Qin, J.J.O'Leary, A.W.Tolcher. A phase I dose-escalation study of IMGN388 in patients with solid tumors. ASCO Meeting Abstracts 2010; 28:3058
92. K.R.Kelly, A.Chanan-Khan, L.T.Heffner, G.Somlo, D.S.Siegel, T.Zimmerman, A.Karnad, N.C.Munshi, S.Jagannath, A.L.Greenberg, et al. Indatuximab ravtansine (BT062) in combination with lenalidomide and low-dose dexamethasone in patients with relapsed and/or refractory multiple myeloma: Clinical activity in patients already exposed to lenalidomide and bortezomib. Blood 2014; 124:4736
93. S.Jagannath, A.Chanan-Khan, L.T.Heffner, D.Avigan, T.M.Zimmerman, S.Lonial, R.J.Lutz, A.Engling, C.Uherek, F.Osterroth, et al. BT062, an antibody-drug conjugate directed against CD138, shows clinical activity in patients with relapsed or Relapsed/Refractory multiple myeloma. ASH Annual Meeting Abstracts 2011; 118:305
94. M.N.Saleh, S.Sugarman, J.Murray, J.B.Ostroff, D.Healey, D.Jones, C.R.Daniel, D.LeBherz, H.Brewer, N.Onetto, et al. Phase I trial of the anti-lewis Y drug immunoconjugate BR96-doxorubicin in patients with lewis Y-expressing epithelial tumors. J Clin Oncol 2000; 18:2282-92; PMID:10829049
95. T.K.Owonikoko, A.Hussain, W.M.Stadler, D.C.Smith, M.Sznol, A.M.Molina, P.Gulati, A.Shah, C.M.Ahlers, J.Cardarelli, et al. A phase 1 multicenter open-label dose-escalation study of BMS-936561 (MDX-1203) in clear cell renal cell carcinoma (ccRCC) and B-cell non hodgkin lymphoma (B-NHL). ASCO Meeting Abstracts 2014; 32:2558
96. I.E.Krop, S.B.Kim, A.Gonzalez-Martin, P.M.LoRusso, J.M.Ferrero, M.Smitt, R.Yu, A.C.Leung, H.Wildiers. TH3RESA study collaborators. Trastuzumab emtansine versus treatment of physician's choice for pretreated HER2-positive advanced breast cancer (TH3RESA): A randomised, open-label, phase 3 trial. Lancet Oncol 2014; 15:689-99; PMID:24793816
97. S.A.Hurvitz, L.Dirix, J.Kocsis, G.V.Bianchi, J.Lu, J.Vinholes, E.Guardino, C.Song, B.Tong, V.Ng, et al. Phase II randomized study of trastuzumab emtansine versus trastuzumab plus docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer. J Clin Oncol 2013; 31:1157-63; PMID:23382472; http://dx.doi.org/10.1200/JCO.2012.44.9694
98. S.Verma, D.Miles, L.Gianni, I.E.Krop, M.Welslau, J.Baselga, M.Pegram, D.Y.Oh, V.Dieras, E.Guardino, et al. Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med 2012; 367:1783-91; PMID:23020162; http://dx.doi.org/10.1056/NEJMoa1209124