Semi-mechanistic multiple-analyte pharmacokinetic model for an antibody-drug-conjugate in cynomolgus monkeys

Pharmaceutical Research

Volumn 32, Issue 6, 2015, Pages 1907-1919

  Lu, Dan ^a   Jin, Jin Yan ^a   Girish, Sandhya ^a   Agarwal, Priya ^a   Li, Dongwei ^a   Prabhu, Saileta ^a   Dere, Randall C ^a   Saad, Ola M ^a   Nazzal, Denise ^a   Koppada, Neelima ^a   Ramanujan, Saroja ^a   Ng, Chee M ^b,c  

^a GENENTECH INC   (United States)

^b UNIVERSITY OF PENNSYLVANIA   (United States)

^c CHILDREN S HOSPITAL OF PHILADELPHIA   (United States)

Author keywords

Antibody drug conjugate; Integrated modeling; Multiple analytes; Pharmacokinetics

Indexed keywords

ANTIBODY; VEDOTIN; ANTINEOPLASTIC AGENT; MONOCLONAL ANTIBODY; OLIGOPEPTIDE;

ARTICLE; CONJUGATE; DEGRADATION; DRUG CLEARANCE; DRUG ELIMINATION; DRUG RELEASE; IN VIVO STUDY; MACACA FASCICULARIS; NONHUMAN; PERIPHERAL VOLUME OF DISTRIBUTION; PRIORITY JOURNAL; SYSTEMIC CIRCULATION; ANIMAL; BIOLOGICAL MODEL; BIOTRANSFORMATION; BLOOD; INTRAVENOUS DRUG ADMINISTRATION; PROTEIN DEGRADATION;

ADMINISTRATION, INTRAVENOUS; ANIMALS; ANTIBODIES, MONOCLONAL, HUMANIZED; ANTINEOPLASTIC AGENTS; BIOTRANSFORMATION; MACACA FASCICULARIS; MODELS, BIOLOGICAL; OLIGOPEPTIDES; PROTEOLYSIS;

EID: 84935020488     PISSN: 07248741     EISSN: 1573904X     Source Type: Journal    
DOI: 10.1007/s11095-014-1585-y     Document Type: Article

References (30)

1. Kadcyla. (ado-trastuzumab emtansine) [package insert]. South San Francisco, CA: Genentech, Inc.; 2013.
2. Adcetris. (Brentuximab vedotin, SGN-35) [package insert]. Bothell, WA: Seattle Genetics, Inc.; 2011.
3. Prabhu S, Boswell CA, Leipold D, Khawli LA, Li D, Lu D, et al. Antibody delivery of drugs and radionuclides: factors influencing clinical pharmacology. Ther Deliv. 2011;2(6):769-91.
4. Hughes B. Antibody-drug conjugates for cancer: poised to deliver? Nat Rev Drug Discov. 2010;9(9):665-7.
5. Palanca-Wessels MC, Flinn IW, Sehn LH, Patel M, Sangha R, Czuczman MS, et al. A Phase I Study of the Anti-CD79b Antibody-Drug Conjugate (ADC) DCDS4501A Targeting CD79b in Relapsed or Refractory B-Cell Non-Hodgkin's Lymphoma (NHL). Blood. 2012;120(14).
6. Shen BQ, Bumbaca D, Saad O, Yue Q, Pastuskovas CV, Khojasteh SC, et al. Catabolic fate and pharmacokinetic characterization of trastuzumab emtansine (T-DM1): an emphasis on preclinical and clinical catabolism. Curr Drug Metab. 2012;13(7):901-10.
7. Lu D, Sahasranaman S, Zhang Y, Girish S. Strategies to address drug interaction potential for antibody-drug conjugates in clinical development. Bioanalysis. 2013;5(9):1115-30.
8. Shen BQ, Xu K, Liu L, Raab H, Bhakta S, Kenrick M, et al. Conjugation sitemodulates the in vivo stability and therapeutic activity of antibody-drug conjugates. Nat Biotechnol. 2012;30(2):184-9.
9. Bender B, Leipold DD, Xu K, Shen BQ, Tibbitts J, Friberg LE. A mechanistic pharmacokinetic model elucidating the disposition of trastuzumab emtansine (T-DM1), an antibody-drug conjugate (ADC) for treatment of metastatic breast cancer. AAPS J. 2014;16(5):994-1008.
10. Lu D, Joshi A, Wang B, Olsen S, Yi JH, Krop IE, et al. An integrated multiple-analyte pharmacokineticmodel to characterize trastuzumab emtansine (T-DM1) clearance pathways and to evaluate reduced pharmacokinetic sampling in patients with HER2-positive metastatic breast cancer. Clin Pharmacokinet. 2013;52(8):657-72.
11. Chudasama VL, Schaedeli Stark F, Harrold JM, Tibbitts J, Girish SR, Gupta M, et al. Semi-mechanistic population pharmacokinetic model of multivalent trastuzumab emtansine in patients with metastatic breast cancer. Clin Pharmacol Ther. 2012;92(4):520-7.
12. Dornan D, Bennett F, Chen Y, Dennis M, Eaton D, Elkins K, 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(13):2721-9.
13. Polson AG, Yu SF, Elkins K, Zheng B, Clark S, Ingle GS, et al. Antibody-drug conjugates targeted to CD79 for the treatment of non-Hodgkin lymphoma. Blood. 2007;110(2):616-23.
14. Polson AG, Calemine-Fenaux J, Chan P, Chang W, Christensen E, Clark S, et al. Antibody-drug conjugates for the treatment of non-Hodgkin's lymphoma: target and linker-drug selection. Cancer Res. 2009;69(6):2358-64.
15. Zheng B, Fuji RN, Elkins K, Yu SF, Fuh FK, Chuh J, et al. In vivo effects of targeting CD79b with antibodies and antibody-drug conjugates. Mol Cancer Ther. 2009;8(10):2937-46.
16. Kaur S, Xu K, Saad OM, Dere RC, Carrasco-Triguero M. Bioanalytical assay strategies for the development of antibody-drug conjugate biotherapeutics. Bioanalysis. 2013;5(2):201-26.
17. Bauer RJ, Guzy S. Monte Carlo Parametric Expectation Maximization (MC-PEM) method for analyzing population pharmacokinetic/pharmacodynamic (PK/PD) data. In: D'Argenio DZ, editor. Advanced methods of pharmacokinetic and pharamcodynamic system analysis. Boston: Kluwer Academic Publishers; 2004. p. 135-63.
18. Ng CM, Joshi A, Dedrick RL, Garovoy MR, Bauer RJ. Pharmacokinetic-pharmacodynamic-efficacy analysis of efalizumab in patients withmoderate to severe psoriasis. PharmRes. 2005;22(7): 1088-100.
19. Schwarz GE. Estimating the dimension of a model. Ann Stat. 1978;6(2):461-4.
20. Ng CM, Bai S, Takimoto CH, TangMT, TolcherAW.Mechanismbased receptor-binding model to describe the pharmacokinetic and pharmacodynamic of an anti-alpha5beta1 integrin monoclonal antibody (volociximab) in cancer patients. Cancer Chemother Pharmacol. 2010;65(2):207-17.
21. Dirks NL, Meibohm B. Population pharmacokinetics of therapeutic monoclonal antibodies. Clin Pharmacokinet. 2010;49(10):633-59.
22. Gregersen MI, Sear H, Rawson RA, Chien S, Saiger GL. Cell volume, plasma volume, total blood volume and F cells factor in the rhesus monkey. Am J Physiol. 1959;196(1):184-7.
23. Adem YT, Schwarz KA, Duenas E, Patapoff TW, Galush WJ, Esue O. Auristatin antibody drug conjugate physical instability and the role of drug payload. Bioconjug Chem. 2014;25(4): 656-64.
24. Hamblett KJ, Senter PD, Chace DF, Sun MM, Lenox J, Cerveny CG, et al. Effects of drug loading on the antitumor activity of a monoclonal antibody drug conjugate. Clin Cancer Res Off J Am Assoc Cancer Res. 2004;10(20):7063-70.
25. Leipold D, Bender B, Xu K, Theil FP, Tibbitts J. Understanding the deconjugation of Trastuzumab-MCCDM1 through application of a multi-compartmental model of individual drug:antibody species in cynomolgus monkey [abstract no. 2914]. American Association for Cancer Research (AACR) Meeting; Apr 18; Denver, CO2009.
26. Beal SL. Ways to fit a PK model with some data below the quantification limit. J Pharmacokinet Pharmacodyn. 2001;28(5):481-504.
27. Ng CM, Loyet KM, Iyer S, Fielder PJ, Deng R. Modeling approach to investigate the effect of neonatal Fc receptor binding affinity and anti-therapeutic antibody on the pharmacokinetic of humanized monoclonal anti-tumor necrosis factor-alpha IgG antibody in cynomolgus monkey. Eur J PharmSciOff J Eur Fedr PharmSci. 2014;51: 51-8.
28. Shah DK, King LE, Han X, Wentland JA, Zhang Y, Lucas J, et al. A priori prediction of tumor payload concentrations: preclinical case study with an auristatin-based anti-5T4 antibody-drug conjugate. AAPS J. 2014;16(3):452-63.
29. Chen Y, Samineni D,Mukadam S, Wong H, Shen BQ, Lu D, et al. Physiologically Based PharmacokineticModeling as a Tool to Predict Drug Interactions for Antibody-Drug Conjugates. Clin Pharmacokinet. 2014.
30. FDA. The U.S. FDA clinical pharmacology and biopharmaceutics review for Brentuximab vedotin. 2011 [cited 2014 July 7]; Available from: http://www.accessdata.fda.gov/drugsatfda-docs/nda/2011/125388Orig1s000ClinPharmR.pdf.