Fractionated dosing improves preclinical therapeutic index of pyrrolobenzodiazepine-containing antibody drug conjugates

Clinical Cancer Research

Volumn 23, Issue 19, 2017, Pages 5858-5868

  Hinrichs, Mary Jane Masson ^a   Ryan, Pauline M ^a   Zheng, Bo ^a   Afif Rider, Shameen ^a   Yu, Xiang Qing ^a   Gunsior, Michele ^a   Zhong, Haihong ^a   Harper, Jay ^a   Bezabeh, Binyam ^a   Vashisht, Kapil ^a   Rebelatto, Marlon ^a   Reed, Molly ^a   Ryan, Patricia C ^a   Breen, Shannon ^a   Patel, Neki ^b   Chen, Cui ^a   Masterson, Luke ^b   Tiberghien, Arnaud ^b   Howard, Phillip W ^b   Dimasi, Nazzareno ^a   Dixit, Rakesh ^a   more..

^a MEDIMMUNE   (United States)

^b ASTRAZENECA   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIBODY DRUG CONJUGATE; BENZODIAZEPINE DERIVATIVE; PYRROLOBENZODIAZEPINE; UNCLASSIFIED DRUG; ANTIBODY CONJUGATE; MONOCLONAL ANTIBODY; PYRROLE DERIVATIVE; PYRROLO(2,1-C)(1,4)BENZODIAZEPINE; TRASTUZUMAB;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; AREA UNDER THE CURVE; ARTICLE; BODY WEIGHT; BREAST CANCER; CANCER INHIBITION; CANCER SURVIVAL; CONTROLLED STUDY; DOSAGE SCHEDULE COMPARISON; DOSE RESPONSE; DRUG EFFICACY; DRUG HALF LIFE; DRUG SAFETY; DRUG TOLERABILITY; FEMALE; MACACA FASCICULARIS; MALE; MAXIMUM PLASMA CONCENTRATION; MOUSE; NONHUMAN; OUTCOME ASSESSMENT; PRIORITY JOURNAL; PROSTATE CANCER; RAT; STOMACH CANCER; TOXICITY TESTING; ANIMAL; BREAST TUMOR; CHEMISTRY; DISEASE MODEL; DRUG SCREENING; HAPLORHINI; HUMAN; IMMUNOLOGY; PATHOLOGY; PROSTATE TUMOR; THERAPEUTIC INDEX; TUMOR CELL LINE;

ANIMALS; ANTIBODIES, MONOCLONAL; BENZODIAZEPINES; BREAST NEOPLASMS; CELL LINE, TUMOR; DISEASE MODELS, ANIMAL; DOSE-RESPONSE RELATIONSHIP, DRUG; FEMALE; HAPLORHINI; HUMANS; IMMUNOCONJUGATES; MALE; MICE; PROSTATIC NEOPLASMS; PYRROLES; RATS; THERAPEUTIC INDEX; TRASTUZUMAB; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 85032256094     PISSN: 10780432     EISSN: 15573265     Source Type: Journal    
DOI: 10.1158/1078-0432.CCR-17-0219     Document Type: Article

References (46)

1. Mullard A. Maturing antibody-drug conjugate pipeline hits 30. Nat Rev Drug Discov 2013;12:329–32.
2. Sassoon I, Blanc V. Antibody–drug conjugate (ADC) clinical pipeline: a review. In:Ducry L, editor.Antibody-drug conjugates. Totowa, NJ: Humana Press; 2013. p. 1–27.
3. Donaghy H.Effects of antibody, drug and linker on the preclinical and clinical toxicities of antibody-drug conjugates. mAbs 2016;8:659–71.
4. Castaigne S, Pautas C, Terre C, Raffoux E, Bordessoule D, Bastie JN, 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.
5. Deslandes A.Comparative clinical pharmacokinetics of antibody-drug conjugates in first-in-human Phase 1 studies. mAbs 2014;6:859–70.
6. Beeram M, Krop IE, Burris HA, Girish SR, Yu W, Lu MW, 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 2012;118:5733–40.
7. Fanale MA, Forero-Torres A, Rosenblatt JD, Advani RH, Franklin AR, Kennedy DA, et al. A phase I weekly dosing study of brentuximab vedotin in patients with relapsed/refractory CD30-positive hematologic malignancies. Clin Cancer Res 2012;18:248–55.
8. Younes A, Kim S, Romaguera J, Copeland A, Farial Sde C, Kwak LW, et al. Phase I multidose-escalation study of the anti-CD19 maytansinoid immu-noconjugate SAR3419 administered by intravenous infusion every 3 weeks to patients with relapsed/refractory B-cell lymphoma. J Clin Oncol 2012;30:2776–82.
9. Ribrag V, Dupuis J, Tilly H, Morschhauser F, Laine F, Houot R, 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.
10. Taksin AL, Legrand O, Raffoux E, de Revel T, Thomas X, Contentin N, et al. High efficacy and safety profile of fractionated doses of Mylotarg as induction therapy in patients with relapsed acute myeloblastic leukemia: a prospective study of the alfa group. Leukemia 2006;21:66–71.
11. Peterlin P, Guillaume T, Delaunay J, Mohty M, Garnier A, Mahe B, et al. Similarity of fractionated versus single dose(s) of gemtuzumab ozogamicin as part of the MIDAM salvage regimen in relapsed/refractory acute myeloid leukemia patients. Sem Hematol 2016;53:216–7.
12. Peterlin P, Guillaume T, Delaunay J, Mohty M, Garnier A, Rialland F, et al. No advantages of fractionated versus single dose(s) of gemtuzumab ozogamicin (GO) as part of the midam salvage regimen in relapsed/refractory acute myeloid leukemia (AML) patients. Blood 2015;126:2520.
13. Wilkinson GP, Taylor JP, Shnyder S, Cooper P, Howard PW, Thurston DE, et al. Preliminary pharmacokinetic and bioanalytical studies of SJG-136 (NSC 694501), a sequence-selective pyrrolobenzodiazepine dimer DNA-cross-linking agent. Invest New Drugs 2004;22:231–40.
14. Rudin CM, Pietanza MC, Bauer TM, Spigel DR, Ready N, Morgensztern D, et al. Safety and efficacy of single-agent rovalpituzumab tesirine (SC16LD6.5), a delta-like protein 3 (DLL3)-targeted antibody-drug conjugate (ADC) in recurrent or refractory small cell lung cancer (SCLC). J Clin Oncol 2016;34(Suppl/abstr LBA8505).
15. Stein AS, Walter RB, Erba HP, Fathi AT, Advani AS, Lancet JE, et al. A phase 1 trial of SGN-CD33A as monotherapy in patients with CD33-positive acute myeloid leukemia (AML). Blood 2015;126:324.
16. Jackson D, Gooya J, Mao S, Kinneer K, Xu L, Camara M, et al. A human antibody-drug conjugate targeting EphA2 inhibits tumor growth in vivo. Cancer Res 2008;68:9367–74.
17. Thompson P, Fleming R, Bezabeh B, Huang F, Mao S, Chen C, et al. Rational design, biophysical and biological characterization of site-specific antibody-tubulysin conjugates with improved stability, efficacy and pharmacokinetics. J Controlled Rel 2016;236:100–16.
18. Dimasi N, Fleming R, Zhong H, Bezabeh B, Kinneer K, Christie RJ, et al. Efficient preparation of site-specific antibody–drug conjugates using cysteine insertion. Mol Pharm 2017;14:1501–16.
19. Sapra P, Damelin M, DiJoseph J, Marquette K, Geles KG, Golas J, et al. Long-term tumor regression induced by an antibody–drug conjugate that targets 5T4, an oncofetal antigen expressed on tumor-initiating cells. Mol Cancer Therap 2013;12:38–47.
20. Tiberghien AC, Levy J-N, Masterson LA, Patel NV, Adams LR, Corbett S, et al. Design and synthesis of tesirine, a clinical antibody–drug conjugate pyrrolobenzodiazepine dimer payload. ACS Med Chem Lett 2016;7:983–87.
21. Hartley JA, Spanswick VJ, Brooks N, Clingen PH, McHugh PJ, Hoch-hauser D, et al. SJG-136 (NSC 694501), a novel rationally designed DNA minor groove interstrand cross-linking agent with potent and broad spectrum antitumor activity. Part 1: Cellular pharmacology, in vitro and initial in vivo antitumor activity. Cancer Res 2004;64: 6693–9.
22. Rahman KM, Thompson AS, James CH, Narayanaswamy M, Thurston DE. The pyrrolobenzodiazepine dimer SJG-136 forms sequence-dependent intrastrand DNA cross-links and monoalkylated adducts in addition to interstrand cross-links. J Am Chem Soc 2009;131:13756–66.
23. Ullman-Cullere MH, Foltz CJ. Body condition scoring: a rapid and accurate method for assessing health status in mice. Lab Anim Sci 1999;49:319–23.
24. Clinical Laboratory Parameters for Crl:CD(SD) Rats [Internet]. Charles River Laboratories. 2006 [cited 2016]. Available from:http://www.criver. com/files/pdfs/rms/cd/rm_rm_r_clinical_parameters_cd_rat_06.aspx.
25. Kaplan N, Fatima A, Peng H, Bryar PJ, Lavker RM, Getsios S. EphA2/Ephrin-A1 signaling complexes restrict corneal epithelial cell migration. Invest Ophthal Visual Sci 2012;53:936–45.
26. Dave A, Martin S, Kumar R, Craig JE, Burdon KP, Sharma S. Epha2 mutations contribute to congenital cataract through diverse mechanisms. Mol Vision 2016;22:18–30.
27. Mager DE.Target-mediated drug disposition and dynamics. Biochem Pharmacol 2006;72:1–10.
28. Preclinical safety evaluation of biotechnology-derived pharmaceuticals ICH harmonized tripartite guideline S6(R1), 2011. Available at http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Safety/S6_R1/Step4/S6_R1_Guideline.pdf.
29. Bachelder RE, Bilancieri J, Lin W, Letvin NL. A human recombinant Fab identifies a human immunodeficiency virus type 1-induced conformational change in cell surface-expressed CD4. J Virol 1995;69: 5734–42.
30. Park H-K, Cho J-W, Lee B-S, Park H, Han J-S, Yang M-J, et al. Reference values of clinical pathology parameters in cynomolgus monkeys (Macaca fascicularis) used in preclinical studies. Lab Animal Res 2016;32:79–86.
31. Leal M, Wentland J, Han X, Zhang Y, Rago B, Duriga N, et al. Preclinical Development of an anti-5T4 antibody-drug conjugate: pharmacokinetics in mice, rats, and NHP and tumor/tissue distribution in mice. Bioconjug Chem 2015;26:2223–32.
32. Lee CM, Tannock IF. The distribution of the therapeutic monoclonal antibodies cetuximab and trastuzumab within solid tumors. BMC Cancer 2010;10:255–66.
33. Levison ME, Levison JH. Pharmacokinetics and pharmacodynamics of antibacterial agents. Infect Dis Clin North America 2009;23:791–815, vii.
34. Jumbe NL, Xin Y, Leipold DD, Crocker L, Dugger D, Mai E, et al. Modeling the efficacy of trastuzumab-DM1, an antibody drug conjugate, in mice. J Pharmacokinetics Pharmacodynamics 2010;37:221–42.
35. Govindan SV, Cardillo TM, Rossi EA, Trisal P, McBride WJ, Sharkey RM, et al. Improving the therapeutic index in cancer therapy by using antibody–drug conjugates designed with a moderately cytotoxic drug. Mol Pharm 2015;12:1836–47.
36. Jeffrey SC, Burke PJ, Lyon RP, Meyer DW, Sussman D, Anderson M, et al. A potent anti-CD70 antibody–drug conjugate combining a dimeric pyrrolobenzodiazepine drug with site-specific conjugation technology. Biocon-jugate Chem 2013;24:1256–63.
37. Maziasz T, Kadambi VJ, Silverman L, Fedyk E, Alden CL. Predictive toxicology approaches for small molecule oncology drugs. Toxicol Pathol 2010;38:148–64.
38. Richmond A, Su Y. Mouse xenograft models vs GEM models for human cancer therapeutics. Dis Models Mech 2008;1:78–82.
39. Kamath AV.Translational pharmacokinetics and pharmacodynamics of monoclonal antibodies. Drug Discov Today 2016;21–22:75–83.
40. Voskoglou-Nomikos T, Pater JL, Seymour L. Clinical predictive value of the in vitro cell line, human xenograft, and mouse allograft preclinical cancer models. Clin Cancer Res 2003;9:4227–39.
41. Olson H, Betton G, Robinson D, Thomas K, Mon ro A, Kolaja G, et al. Con cordance of the toxicity of pharmaceutical s i n human s and in ani mals. Reg Toxi col Pharmacol 2000;32: 56–67.
42. Wang Y, Probin V, Zhou D. Cancer therapy-induced residual bone marrow injury-Mechanisms of induction and implication for therapy. Curr Cancer Ther Rev 2006;2:271–9.
43. Clark DL, Andrews PA, Smith DD, DeGeorge JJ, Justice RL, Beitz JG. Predictive value of preclinical toxicology studies for platinum anticancer drugs. Clin Cancer Res 1999;5:1161–7.
44. Kennedy DA, Alley SC, Zhao B, Feldman EJ, O'Meara M, Sutherland M. Abstract DDT02-04: 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). Cancer Res 2015;75: DDT02-4-DDT-4.
45. Patel M, Palani S, Chakravarty A, Yang J, Shyu WC, Mettetal JT. Dose schedule optimization and the pharmacokinetic driver of neutropenia. PloS One 2014;9:e109892.
46. Hinrichs MJ, Dixit R. Antibody drug conjugates: nonclinical safety considerations. AAPS J 2015:1–10.