Preclinical and clinical pharmacokinetic/pharmacodynamic considerations for antibody–drug conjugates

Expert Review of Clinical Pharmacology

Volumn 6, Issue 5, 2013, Pages 541-555

  Sapra, Puja ^a   Betts, Alison ^a   Boni, Joseph ^a  

^a PFIZER INC   (United States)

Author keywords

antibody drug conjugates; calicheamicin; clinical pharmacokinetics; pharmacokinetic pharmacodynamic modeling; tubulin inhibitors

Indexed keywords

ANTIBODY CONJUGATE; ANTINEOPLASTIC AGENT; CAC10-VCMMAE; MAYTANSINE; MONOCLONAL ANTIBODY; TRASTUZUMAB EMTANSINE;

ANALOGS AND DERIVATIVES; ANIMAL; BIOLOGICAL MODEL; CLINICAL TRIAL (TOPIC); DRUG SCREENING; HUMAN; TREATMENT OUTCOME;

ANIMALS; ANTIBODIES, MONOCLONAL, HUMANIZED; ANTINEOPLASTIC AGENTS; CLINICAL TRIALS AS TOPIC; DRUG EVALUATION, PRECLINICAL; HUMANS; IMMUNOCONJUGATES; MAYTANSINE; MODELS, BIOLOGICAL; TREATMENT OUTCOME;

EID: 84893848111     PISSN: 17512433     EISSN: 17512441     Source Type: Journal    
DOI: 10.1586/17512433.2013.827405     Document Type: Review

References (52)

1. Sapra P, Shor B. Monoclonal antibody-based therapies in cancer: Advances and challenges. Pharmacol. Ther. 138 (3), 452–469 (2013).
2. Hamel E. Natural products which interact with tubulin in the vinca domain: maytansine, rhizoxin, phomopsin A, dolastatins 10 and 15 and halichondrin B. Pharmacol. Ther. 55 (1), 31–51 (1992).
3. Petersdorf S, Kopecky K, Stuart RK et al. Preliminary results of southwest oncology group study S0106: An international intergroup phase 3 randomized trial comparing the addition of gemtuzumab ozogamicin to standard induction therapy versus standard induction therapy followed by a second randomization to post-consolidation gemtuzumab ozogamicin versus no additional therapy for previously untreated acute myeloid leukemia. Blood (ASH Annual Meeting Abstracts) 114, abstract nr 790 (2009).
4. Press Release, American Society of Hematology. FDA Announcement of Pfizer Voluntary Withdrawal of Cancer Treatment Mylotarg From U.S. Market. June 21, 2010. [ http://www.hematology.org/News/2010/5381.aspx ]
5. Castaigne S, Pautas C, Terre C 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 379 (9825), 1508–1516 (2012).
6. Van Der Velden VH, Te Marvelde JG, Hoogeveen PG et al. 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 (2001).
7. Linenberger ML. CD33-directed therapy with gemtuzumab ozogamicin in acute myeloid leukemia: progress in understanding cytotoxicity and potential mechanisms of drug resistance. Leukemia 19 (2), 176–182 (2005).
8. Burnett AK, Russell NH, Hills RK et al. Addition of gemtuzumab ozogamicin to induction chemotherapy improves survival in older patients with acute myeloid leukemia. J. Clin. Oncol 30 (32), 3924–3931 (2012).
9. Burnett AK, Hills RK, Milligan D et al. Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial. J. Clin. Oncol. 29 (4), 369–377 (2011).
10. Sievers EL, Larson RA, Stadtmauer EA et al. Efficacy and safety of gemtuzumab ozogamicin in patients with CD33-positive acute myeloid leukemia in first relapse. J. Clin. Oncol. 19 (13), 3244–3254 (2001).
11. Dowell JA, Korth-Bradley J, Liu H, King SP, Berger MS. Pharmacokinetics of gemtuzumab ozogamicin, an antibody-targeted chemotherapy agent for the treatment of patients with acute myeloid leukemia in first relapse. J. Clin. Pharm. 41 (11), 1206–1214 (2001).
12. Korth-Bradley JM, Dowell JA, King SP, Liu H, Berger MS, Mylotarg Study G. Impact of age and gender on the pharmacokinetics of gemtuzumab ozogamicin. Pharmacotherapy 21 (10), 1175–1180 (2001).
13. Kobayashi Y, Tobinai K, Takeshita A et al. Phase I/II study of humanized anti-CD33 antibody conjugated with calicheamicin, gemtuzumab ozogamicin, in relapsed or refractory acute myeloid leukemia: final results of Japanese multicenter cooperative study. Int. J. Hematol. 89 (4), 460–469 (2009).
14. Buckwalter M, Dowell JA, Korth-Bradley J, Gorovits B, Mayer PR. Pharmacokinetics of gemtuzumab ozogamicin as a single-agent treatment of pediatric patients with refractory or relapsed acute myeloid leukemia. J. Clin. Pharmacol. 44 (8), 873–880 (2004).
15. Sievers EL, Appelbaum FR, Spielberger RT et al. Selective ablation of acute myeloid leukemia using antibody-targeted chemotherapy: a phase I study of an anti-CD33 calicheamicin immunoconjugate. Blood 93 (11), 3678–3684 (1999).
16. 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. 28 (12), 2085–2093 (2010).
17. Fayad L, Offner F, Smith MR et al. Safety and clinical activity of a combination therapy comprising two antibody-based targeting agents for the treatment of non-Hodgkin lymphoma: results of a phase I/II study evaluating the immunoconjugate inotuzumab ozogamicin with rituximab. J. Clin. Oncol. 31 (5), 573–583 (2013).
18. Mager DE, Jusko WJ. General pharmacokinetic model for drugs exhibiting target-mediated drug disposition. J. Oharmacokinet. Pharmacodyn. 28 (6), 507–532 (2001).
19. Meijer RT, Koopmans RP, Ten Berge IJ, Schellekens PT. Pharmacokinetics of murine anti-human CD3 antibodies in man are determined by the disappearance of target antigen. J. Pharmacol. Exp. Ther. 300 (1), 346–353 (2002).
20. Friberg LE, Henningsson A, Maas H, Nguyen L, Karlsson MO. Model of chemotherapy-induced myelosuppression with parameter consistency across drugs. J. Clin. Oncol. 20 (24), 4713–4721 (2002).
21. Mugundu G, Vandendries E, Boni J. Use of pharmacokinetic-pharmacodynamic modeling to characterize platelet response following inotuzumab ozogamicin treatment in patients with follicular or diffuse large B-cell non-Hodgkin’s lymphoma. Cancer Res. 72 (Suppl. 8), abstract nr 3767 (2012).
22. Luu K, Vandendries E, Volkert A, Ogura M, Goy A, Boni J. Antitumor response to inotuzumab ozogamicin (INO) in patients with refractory or relapsed indolent B-cell non-Hodgkin’s lymphomas (NHL): Pharmacokinetic-pharmacodynamic (PK-PD) modeling and interim results from a phase II study. Cancer Res. 72 (Suppl. 8), abstract nr 3776 (2012).
23. Kantarjian H, Thomas D, Jorgensen J et al. Inotuzumab ozogamicin, an anti-CD22-calecheamicin conjugate, for refractory and relapsed acute lymphocytic leukaemia: a phase 2 study. Lancet Oncol. 13 (4), 403–411 (2012).
24. O’Brien S, Thomas DA, Jorgensen JL et al. Experience with 2 dose schedules of inotuzumab ozogamicin, single dose, and weekly, in refractory-relapsed Acute Lymphocytic Leukemia (ALL). ASH Ann. Meet. Abstr. 120 (21), 671 (2012).
25. + rituximab in relapsed DLBCL patients followed by stem cell transplantation: Preliminary safety and efficacy. ASH Ann. Meet. Abstr. 116 (21), 2883 - (2010).
26. Ogura M, Uchida T, Macdonald DA et al. An Open-Label, Phase I study of R-CVP in combination with inotuzumab ozogamicin in patients with relapsed/refractory CD22-positive B-cell non-hodgkin lymphoma. ASH Ann. Meet. Abstr. 118 (21), 3715 - (2011).
27. De Claro RA, Mcginn K, Kwitkowski V et al. 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 (2012).
28. Younes A, Bartlett NL, Leonard JP et al. Brentuximab vedotin (SGN-35) for relapsed CD30-positive lymphomas. N. Engl. J. Med. 363 (19), 1812–1821 (2010).
29. Fanale MA, Forero-Torres A, Rosenblatt JD et al. A phase I weekly dosing study of brentuximab vedotin in patients with relapsed/refractory CD30-positive hematologic malignancies. Clin. Cancer Res. 18 (1), 248–255 (2012).
30. Younes A, Gopal AK, Smith SE et al. Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin’s lymphoma. J. Clin. Oncol. 30 (18), 2183–2189 (2012).
31. Pro B, Advani R, Brice P et al. Brentuximab vedotin (SGN-35) in patients with relapsed or refractory systemic anaplastic large-cell lymphoma: results of a phase II study. J. Clin. Oncol. 30 (18), 2190–2196 (2012).
32. Younes A, Connors JM, Park SI, Hunder NNH, Ansell SM. Frontline therapy with brentuximab vedotin combined with ABVD or AVD in patients with newly diagnosed advanced stage Hodgkin lymphoma. Blood (ASH Annual Meeting Abstracts) 118, abstract 955 (2011).
33. Chen R, Palmer JM, Thomas SH et al. Brentuximab vedotin enables successful reduced-intensity allogeneic hematopoietic cell transplantation in patients with relapsed or refractory Hodgkin lymphoma. Blood 119 (26), 6379–6381 (2012).
34. Lee JJ, Swain SM. Peripheral neuropathy induced by microtubule-stabilizing agents. J. Clin. Oncol. 24 (10), 1633–1642 (2006).
35. Swain SM, Arezzo JC. Neuropathy associated with microtubule inhibitors: diagnosis, incidence, and management. Clin. Adv. Hematol. Oncol. 6 (6), 455–467 (2008).
36. 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. 28 (16), 2698–2704 (2010).
37. Beeram M, Krop IE, Burris HA et al. A phase 1 study of weekly dosing of trastuzumab emtansine (T-DM1) in patients with advanced human epidermal growth factor 2-positive breast cancer. Cancer 118 (23), 5733–5740. (2012).
38. Burris HA, Rugo HS, Vukelja SJ et al. 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 (2011).
39. Krop IE, Lorusso P, Miller KD et al. A phase II study of trastuzumab emtansine in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer who were previously treated with trastuzumab, lapatinib, an anthracycline, a taxane, and capecitabine. J. Clin. Oncol. 30 (26), 3234–3241 (2012).
40. Hurvitz SA, Dirix L, Kocsis J 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. 31 (9), 1157–1163 (2013).
41. Verma S, Miles D, Gianni L et al. Trastuzumab emtansine for HER2-positive advanced breast cancer. N. Engl. J. Med. 367 (19), 1783–1791 (2012).
42. Bender BC, Schaedeli-Stark F, Koch R et al. A population pharmacokinetic/pharmacodynamic model of thrombocytopenia characterizing the effect of trastuzumab emtansine (T-DM1) on platelet counts in patients with HER2-positive metastatic breast cancer. Cancer Chemother. Pharm. 70 (4), 591–601 (2012).
43. Kola I, Landis J. Can the pharmaceutical industry reduce attrition rates? Nat. Rev. Drug Discov. 3 (8), 711–715 (2004).
44. Arrowsmith J. Trial watch: Phase II failures: 2008–2010. Nat. Rev. Drug Discov. 10 (5), 328–329 (2011).
45. Rajman I. PK/PD modelling and simulations: utility in drug development. Drug Discov. Today 13 (7–8), 341–346 (2008).
46. Gobburu JV, Lesko LJ. Quantitative disease, drug, and trial models. Ann. Rev. Pharm. Toxicol. 49, 291–301 (2009).
47. Van Der Graaf PH, Gabrielsson J. Pharmacokinetic-pharmacodynamic reasoning in drug discovery and early development. Fut. Med. Chem. 1 (8), 1371–1374 (2009).
48. Agoram BM, Martin SW, Van Der Graaf PH. The role of mechanism-based pharmacokinetic-pharmacodynamic (PK-PD) modelling in translational research of biologics. Drug Discov. Today 12 (23–24), 1018–1024 (2007).
49. Jumbe NL, Xin Y, Leipold DD et al. Modeling the efficacy of trastuzumab-DM1, an antibody drug conjugate, in mice. J. Pharm. Pharm. 37 (3), 221–242 (2010).
50. Simeoni M, Magni P, Cammia C et al. Predictive pharmacokinetic-pharmacodynamic modeling of tumor growth kinetics in xenograft models after administration of anticancer agents. Cancer Res. 64 (3), 1094–1101 (2004).
51. Haddish-Berhane N, Shah DK, Ma D et al. On translation of antibody drug conjugates efficacy from mouse experimental tumors to the clinic: a PK/PD approach. J. Pharm. Pharm. (2013) (In Press).
52. Shah DK, Haddish-Berhane N, Betts A. Bench to bedside translation of antibody drug conjugates using a multiscale mechanistic PK/PD model: a case study with brentuximab-vedotin. J. Pharm. Pharm. 39 (6), 643–659 (2012).