Pharmacokinetics and ADME characterizations of antibody-drug conjugates

Methods in Molecular Biology

Volumn 1045, Issue , 2013, Pages 117-131

  Lin, Kedan ^a   Tibbitts, Jay ^b   Shen, Ben Quan ^a  

^a GENENTECH INC   (United States)

^b UCB PHARMA   (Belgium)

Author keywords

Absorption, distribution, metabolism, and excretion (ADME); Antibody drug conjugates (ADCs); Clearance; Drug to antibody ratio (DAR); Optimization; Pharmacodynamics; Pharmacokinetics; Volume of distribution

Indexed keywords

ANTIBODY DRUG CONJUGATE; CALICHEAMICIN; CYTOTOXIC AGENT; DRUG ANTIBODY; GEMTUZUMAB OZOGAMICIN; MONOCLONAL ANTIBODY; UNCLASSIFIED DRUG;

ARTICLE; BIOLOGICAL ACTIVITY; CATABOLISM; DRUG ABSORPTION; DRUG CLEARANCE; DRUG DEGRADATION; DRUG DISTRIBUTION; DRUG EXCRETION; DRUG METABOLISM; DRUG RELEASE; ENZYMATIC DEGRADATION; GLOMERULUS FILTRATION; NONHUMAN; PINOCYTOSIS; PRIORITY JOURNAL; TISSUE DISTRIBUTION; URINARY EXCRETION;

EID: 84934438663     PISSN: 10643745     EISSN: None     Source Type: Book Series    
DOI: 10.1007/978-1-62703-541-5_7     Document Type: Article

References (50)

1. Carter PJ, Senter PD (2008) Antibody-drug conjugates for cancer therapy. Cancer J 14 (3):154-169
2. Schrama D, Reisfeld RA, Becker JC (2006) Antibody targeted drugs as cancer therapeutics. Nat Rev 5(2):147-159
3. Decarvalho S, Rand HJ, Lewis A (1964) Coupling of cyclic chemotherapeutic compounds to immune gamma-globulins. Nature 202:255-258
4. de Claro RA, McGinn KM, Kwitkowski VE, Bullock J, Khandelwal A, Habtemariam BA, Ouyang Y, Saber H, Lee K, Koti K, Rothmann MD, Shapiro M, Borrego F, Clouse K, Chen XH, Brown J, Akinsanya L, Kane RC, Kaminskas E, Farrell A, Pazdur R (2012) U.S. Food and Drug Administration approval summary: Brentuximab vedotin for the treatment of relapsed Hodgkin lymphoma or relapsed systemic anaplastic large cell lymphoma. Clin Cancer Res 18(21):5845-5849. doi:10.1158/ 1078-0432.CCR-12-1803
5. Blackwell K (2012) Primary results from EMILIA, a phase III study of trastuzumab emtansine (T-DM1) versus capecitabine (X) and lapatinib (L) in HER2-positive locally advanced or metastatic breast cancer (MBC) previously treated with trastuzumab (T) and a taxane. In: 2012 ASCO annual meeting 2012. J Clin Oncol vol 30, 2012 (suppl; abstr LBA1
6. Lobo ED, Hansen RJ, Balthasar JP (2004) Antibody pharmacokinetics and pharmacodynamics. J Pharm Sci 93(11):2645-2668. doi:10.1002/jps.20178
7. Deng R, Jin F, Prabhu S, Iyer S (2012) Monoclonal antibodies: What are the pharmacokinetic and pharmacodynamic considerations for drug development? Expert Opin Drug Metab Toxicol 8(2):141-160. doi:10.1517/ 17425255.2012.643868
8. Lin K, Tibbitts J (2012) Pharmacokinetic considerations for antibody drug conjugates. Pharm Res 29(9):2354-2366. doi:10.1007/ s11095-012-0800-y
9. Singh R, Erickson HK (2009) Antibodycytotoxic agent conjugates: Preparation and characterization. Methods Mol Biol 525:445-467, xiv. doi:10.1007/978-1-59745-554-1-23
10. Hamblett KJ, Senter PD, Chace DF, Sun MM, Lenox J, Cerveny CG, Kissler KM, Bernhardt SX, Kopcha AK, Zabinski RF, Meyer DL, Francisco JA (2004) Effects of drug loading on the antitumor activity of a monoclonal antibody drug conjugate. Clin Cancer Res 10 (20):7063-7070
11. Girish S, Gupta M, Wang B, Lu D, Krop IE, Vogel CL, Burris Iii HA, Lorusso PM, Yi JH, Saad O, Tong B, Chu YW, Holden S, Joshi A (2012) Clinical pharmacology of trastuzumab emtansine (T-DM1): An antibody-drug conjugate in development for the treatment of HER2-positive cancer. Cancer Chemother Pharmacol 69(5):1229-1240. doi:10.1007/ s00280-011-1817-3
12. Tabrizi M, Bornstein GG, Suria H (2010) Biodistribution mechanisms of therapeutic monoclonal antibodies in health and disease. AAPS J 12(1):33-43. doi:10.1208/s12248-009-9157-5
13. Mould DR, Green B (2010) Pharmacokinetics and pharmacodynamics of monoclonal antibodies: Concepts and lessons for drug development. BioDrugs 24(1):23-39. doi:10.2165/ 11530560-000000000-00000
14. Tabrizi MA, Tseng CM, Roskos LK (2006) Elimination mechanisms of therapeutic monoclonal antibodies. Drug Discov Today 11 (1-2):81-88
15. Boswell CA, Mundo EE, Zhang C, Bumbaca D, Valle NR, Kozak KR, Fourie A, Chuh J, Koppada N, Saad O, Gill H, Shen BQ, Rubinfeld B, Tibbitts J, Kaur S, Theil FP, Fielder PJ, Khawli LA, Lin K (2011) Impact of drug conjugation on pharmacokinetics and tissue distribution of anti-STEAP1 antibody-drug conjugates in rats. Bioconjug Chem 22(10):1994-2004. doi:10.1021/ bc200212a
16. Tolcher AW, Ochoa L, Hammond LA, Patnaik A, Edwards T, Takimoto C, Smith L, de Bono J, Schwartz G, Mays T, Jonak ZL, Johnson R, DeWitte M, Martino H, Audette C, Maes K, Chari RV, Lambert JM, Rowinsky EK (2003) Cantuzumab mertansine, a maytansinoid immunoconjugate directed to the CanAg antigen: A phase I, pharmacokinetic, and biologic correlative study. J Clin Oncol 21(2):211-222
17. Pastuskovas CV, Mallet W, Clark S, Kenrick M, Majidy M, Schweiger M, Van Hoy M, Tsai SP, Bennett G, Shen BQ, Ross S, Fielder P, Khawli L, Tibbitts J (2010) Effect of immune complex formation on the distribution of a novel antibody to the ovarian tumor antigen CA125. Drug Metab Dispos 38(12):2309-2319. doi:10.1124/dmd.110.034330
18. XieH, Audette C, Hoffee M, Lambert JM, Blattler WA (2004) Pharmacokinetics and biodistribution of the antitumor immunoconjugate, cantuzumab mertansine (huC242-DM1), and its two components in mice. J Pharmacol Exp Ther 308(3):1073-1082
19. Sapra P, Stein R, Pickett J, Qu Z, Govindan SV, Cardillo TM, Hansen HJ, Horak ID, Griffiths GL, Goldenberg DM (2005) Anti-CD74 antibody-doxorubicin conjugate, IMMU-110, in a human multiple myeloma xenograft and in monkeys. Clin Cancer Res 11(14):5257-5264. doi:10.1158/1078-0432.CCR-05-0204
20. Henry MD, Wen S, Silva MD, Chandra S, Milton M, Worland PJ (2004) A prostate-specific membrane antigen-targeted monoclonal antibody-chemotherapeutic conjugate designed for the treatment of prostate cancer. Cancer Res 64(21):7995-8001
21. Rupp U, Schoendorf-Holland E, Eichbaum M, Schuetz F, Lauschner I, Schmidt P, Staab A, Hanft G, Huober J, Sinn HP, Sohn C, Schneeweiss A (2007) Safety and pharmacokinetics of bivatuzumab mertansine in patients with CD44v6-positive metastatic breast cancer: Final results of a phase I study. Anticancer Drugs 18(4):477-485
22. Tijink BM, Buter J, de Bree R, Giaccone G, Lang MS, Staab A, Leemans CR, van Dongen GA (2006) 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 12(20 Pt 1):6064-6072
23. BurrisHA3rd, Rugo HS, Vukelja SJ, Vogel CL, Borson RA, Limentani S, Tan-Chiu E, Krop IE, Michaelson RA, Girish S, Amler L, Zheng M, Chu YW, Klencke B, O'Shaughnessy JA (2011) Phase II study of the antibody drug conjugate trastuzumab-DM1 for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer after prior HER2-directed therapy. J Clin Oncol 29(4):398-405. doi:10.1200/JCO.2010.29.5865
24. Advani A, Coiffier B, Czuczman MS, Dreyling M, Foran J, Gine E, Gisselbrecht C, Ketterer N, Nasta S, Rohatiner A, Schmidt-Wolf IG, Schuler M, Sierra J, Smith MR, Verhoef G, Winter JN, Boni J, Vandendries E, Shapiro M, Fayad L (2010) 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 28(12):2085-2093. doi:10.1200/JCO.2009. 25.1900
25. Sanderson RJ, Hering MA, James SF, Sun MM, Doronina SO, Siadak AW, Senter PD, Wahl AF (2005) In vivo drug-linker stability of an anti-CD30 dipeptide-linked auristatin immunoconjugate. Clin Cancer Res 11(2 Pt 1):843-852, doi:11/2/843 [pii]
26. DornanD, Bennett F, Chen Y,DennisM, Eaton D, Elkins K, French D, Go MA, Jack A, Junutula JR, Koeppen H, Lau J, McBride J, Rawstron A, Shi X, Yu N, Yu SF, Yue P, Zheng B, Ebens A, Polson AG (2009) Therapeutic potential of an anti-CD79b antibody-drug conjugate, anti-CD79b-vc-MMAE, for the treatment of non-Hodgkin lymphoma. Blood 114 (13):2721-2729, doi:blood-2009-02-205500 [pii]10.1182/blood-2009-02-205500
27. Lewis Phillips GD, Li G, Dugger DL, Crocker LM, Parsons KL, Mai E, Blattler WA, Lambert JM, ChariRV, LutzRJ,WongWL, JacobsonFS, Koeppen H, Schwall RH, Kenkare-Mitra SR, Spencer SD, Sliwkowski MX (2008) Targeting HER2-positive breast cancer with trastuzumab-DM1, an antibody-cytotoxic drug conjugate. Cancer Res 68(22):9280-9290
28. Shen BQ, Bumbaca D, Saad O, Yue Q, Pastuskovas CV, Khojasteh SC, Tibbitts J, Kaur S, Wang B, Chu YW, Lorusso PM, Girish S (2012) Catabolic fate and pharmacokinetic characterization of trastuzumab emtansine (T-DM1): An emphasis on preclinical and clinical catabolism. Curr Drug Metab 13(7):901-910
29. van Der Velden VH, te Marvelde JG, Hoogeveen PG, Bernstein ID, Houtsmuller AB, Berger MS, van Dongen JJ (2001) Targeting of the CD33-calicheamicin immunoconjugate Mylotarg (CMA-676) in acute myeloid leukemia: In vivo and in vitro saturation and internalization by leukemic and normal myeloid cells. Blood 97 (10):3197-3204
30. Ducry L, Stump B (2010) Antibody-drug conjugates: Linking cytotoxic payloads to monoclonal antibodies. Bioconjug Chem 21 (1):5-13. doi:10.1021/bc9002019
31. Erickson HK, Park PU,Widdison WC, Kovtun YV, Garrett LM, Hoffman K, Lutz RJ, Goldmacher VS, Blattler WA (2006) Antibody-maytansinoid conjugates are activated in targeted cancer cells by lysosomal degradation and linker-dependent intracellular processing. Cancer Res 66(8):4426-4433
32. Alley SC, Benjamin DR, Jeffrey SC, Okeley NM, Meyer DL, Sanderson RJ, Senter PD (2008) Contribution of linker stability to the activities of anticancer immunoconjugates. Bioconjug Chem 19(3):759-765
33. Alley SC, Zhang X, Okeley NM, Anderson M, Law CL, Senter PD, Benjamin DR (2009) The pharmacologic basis for antibody-Auristatin conjugate activity. J Pharmacol Exp Ther 330 (3):932-938
34. Erickson HK, Lambert JM (2012) ADME of antibody-maytansinoid conjugates. AAPS J. doi:10.1208/s12248-012-9386-x
35. Boswell CA, Mundo EE, Zhang C, Stainton SL, Yu SF, Lacap JA, Mao W, Kozak KR, Fourie A, Polakis P, Khawli LA, Lin K (2012) Differential effects of predosing on tumor and tissue uptake of an 111in-labeled anti-TENB2 antibody-drug conjugate. J Nucl Med. doi:10.2967/jnumed.112.103168
36. Boswell CA, Mundo EE, Firestein R, Zhang C, MaoW, Gill H, Young C, Ljumanovic N, Stainton S, Ulufatu S, Fourie A, Kozak KR, Fuji R, Polakis P, Khawli LA, Lin K (2012) An integrated approach to identify normal tissue expression of targets for antibody drug conjugates: Case study of TENB2. Br J Pharmacol. doi:10.1111/j.1476-5381.2012.02138.x
37. Lin YS, Nguyen C, Mendoza JL, Escandon E, Fei D, Meng YG, Modi NB (1999) Preclinical pharmacokinetics, interspecies scaling, and tissue distribution of a humanized monoclonal antibody against vascular endothelial growth factor. J Pharmacol Exp Ther 288(1):371-378
38. Braeckman R (ed) (2000) Pharmacokinetics and pharmacodynamics of protein therapeutics, vol 101. Peptide and Protein Drug Analysis. Marcel Dekker, New York
39. Sands H, Jones PL (1987) Methods for the study of the metabolism of radiolabeled monoclonal antibodies by liver and tumor. J Nucl Med 28(3):390-398
40. Erickson HK, Widdison WC, Mayo MF, Whiteman K, Audette C, Wilhelm SD, Singh R (2010) Tumor delivery and in vivo processing of disulfide-linked and thioether-linked antibody-maytansinoid conjugates. Bioconjug Chem 21(1):84-92
41. OkeleyNM,Miyamoto JB, Zhang X, Sanderson RJ, Benjamin DR, Sievers EL, Senter PD, Alley SC (2010) Intracellular activation of SGN-35, a potent anti-CD30 antibody-drug conjugate. Clin Cancer Res 16(3):888-897
42. Sutherland MS, Sanderson RJ, Gordon KA, Andreyka J, Cerveny CG, Yu C, Lewis TS, Meyer DL, Zabinski RF, Doronina SO, Senter PD, Law CL, Wahl AF (2006) Lysosomal trafficking and cysteine protease metabolism confer target-specific cytotoxicity by peptidelinked anti-CD30-Auristatin conjugates. J Biol Chem 281(15):10540-10547
43. Austin CD, Wen X, Gazzard L, Nelson C, Scheller RH, Scales SJ (2005) Oxidizing potential of endosomes and lysosomes limits intracellular cleavage of disulfide-based antibody-drug conjugates. Proc Natl Acad Sci USA 102(50):17987-17992. doi:10.1073/ pnas.0509035102
44. Girish S, Martin SW, Peterson MC, Zhang LK, Zhao H, Balthasar J, Evers R, Zhou H, Zhu M, Klunk L, Han C, Berglund EG, Huang SM, Joshi A (2011) AAPS workshop report: Strategies to address therapeutic protein-drug interactions during clinical development. AAPS J 13(3):405-416. doi:10.1208/s12248-011-9285-6
45. Lu D, Girish S, Theil F, Joshi A (2012) Pharmacokinetic and pharmacodynamic-based drug interactions for therapeutic proteins. In: Zhou H, Meibohm B (eds) Drug-drug interaction for therapeutic biologics
46. Baillie TA, Cayen MN, Fouda H, Gerson RJ, Green JD, Grossman SJ, Klunk LJ, LeBlanc B, Perkins DG, Shipley LA (2002) Drug metabolites in safety testing. Toxicol Appl Pharmacol 182(3):188-196
47. Smith DA, Obach RS (2009) Metabolites in safety testing (MIST): Considerations of mechanisms of toxicity with dose, abundance, and duration of treatment. Chem Res Toxicol 22(2):267-279. doi:10.1021/tx800415j
48. Bjornsson TD, Callaghan JT, Einolf HJ, Fischer V, Gan L, Grimm S, Kao J, King SP, Miwa G, Ni L, Kumar G, McLeod J, Obach RS, Roberts S, Roe A, Shah A, Snikeris F, Sullivan JT, Tweedie D, Vega JM, Walsh J, Wrighton SA (2003) The conduct of in vitro and in vivo drug-drug interaction studies: A Pharmaceutical Research and Manufacturers of America (PhRMA) perspective. Drug Metab Dispos 31(7):815-832. doi:10.1124/ dmd.31.7.815
49. Drug interaction studies -study design, data analysis, implications for dosing, and labeling recommendations (Draft guidance) (2012) http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/ Guidances/UCM292362.pdf
50. Younes A, Bartlett NL, Leonard JP, Kennedy DA, Lynch CM, Sievers EL, Forero-Torres A (2010) Brentuximab vedotin (SGN-35) for relapsed CD30-positive lymphomas. N Eng J Med 363(19):1812-1821. doi:10.1056/ NEJMoa1002965