Preclinical pharmacokinetics, pharmacodynamics, tissue distribution, and tumor penetration of anti-PD-L1 monoclonal antibody, an immune checkpoint inhibitor

mAbs

Volumn 8, Issue 3, 2016, Pages 593-603

  Deng, Rong ^a   Bumbaca, Daniela ^a   Pastuskovas, Cinthia V ^a   Boswell, C Andrew ^a   West, David ^a,b   Cowan, Kyra J ^a   Chiu, Henry ^a   McBride, Jacqueline ^a   Johnson, Clarissa ^a   Xin, Yan ^a,b   Koeppen, Hartmut ^a   Leabman, Maya ^a   Iyer, Suhasini ^a,c  

^a GENENTECH INC   (United States)

^b GILEAD SCIENCES   (United States)

^c ABBVIE INC   (United States)

Author keywords

Anti PD L1; PD L1; pharmacodynamics; pharmacokinetics; tissue distribution; tumor penetration

Indexed keywords

ATEZOLIZUMAB; CHIMERIC ANTIBODY; IODINE 125; PENTETATE INDIUM IN 111; PRO304397; PROGRAMMED DEATH 1 LIGAND 1; RUBIDIUM 86; TECHNETIUM 99M; UNCLASSIFIED DRUG; CANCER ANTIBODY; CD274 PROTEIN, HUMAN; MONOCLONAL ANTIBODY; TUMOR PROTEIN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; AREA UNDER THE CURVE; ARTICLE; AUTORADIOGRAPHY; CONTROLLED STUDY; DRUG CLEARANCE; DRUG PENETRATION; ENZYME LINKED IMMUNOSORBENT ASSAY; FEMALE; FLOW CYTOMETRY; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; MALE; MOUSE; NONHUMAN; PHARMACODYNAMICS; RADIOACTIVITY; SINGLE DRUG DOSE; TISSUE DISTRIBUTION; ANIMAL; ANTAGONISTS AND INHIBITORS; BAGG ALBINO MOUSE; CELL CYCLE CHECKPOINT; CHO CELL LINE; CRICETULUS; DRUG EFFECTS; HAMSTER; HUMAN; IMMUNOLOGY; MACACA FASCICULARIS; METASTASIS; NEOPLASMS, EXPERIMENTAL; PATHOLOGY; PRECLINICAL STUDY;

ANIMALS; ANTIBODIES, MONOCLONAL; ANTIBODIES, NEOPLASM; ANTIGENS, CD274; CELL CYCLE CHECKPOINTS; CHO CELLS; CRICETINAE; CRICETULUS; DRUG EVALUATION, PRECLINICAL; FEMALE; HUMANS; MACACA FASCICULARIS; MICE; MICE, INBRED BALB C; NEOPLASM METASTASIS; NEOPLASM PROTEINS; NEOPLASMS, EXPERIMENTAL;

EID: 84961664582     PISSN: 19420862     EISSN: 19420870     Source Type: Journal    
DOI: 10.1080/19420862.2015.1136043     Document Type: Article

References (31)

1. R.H.Thompson, S.M.Kuntz, B.C.Leibovich, H.Dong, C.M.Lohse, W.S.Webster, S.Sengupta, I.Frank, A.S.Parker, H.Zincke, et al. Tumor B7-H1 is associated with poor prognosis in renal cell carcinoma patients with long-term follow-up. Cancer Res 2006; 66:3381-5; PMID:16585157; http://dx.doi.org/10.1158/0008-5472.CAN-05-4303
2. R.Hino, K.Kabashima, Y.Kato, H.Yagi, M.Nakamura, T.Honjo, T.Okazaki, Y.Tokura. Tumor cell expression of programmed cell death-1 ligand 1 is a prognostic factor for malignant melanoma. Cancer 2010; 116:1757-66; PMID:20143437; http://dx.doi.org/10.1002/cncr.24899
3. J.Hamanishi, M.Mandai, M.Iwasaki, T.Okazaki, Y.Tanaka, K.Yamaguchi, T.Higuchi, H.Yagi, K.Takakura, N.Minato, et al. Programmed cell death 1 ligand 1 and tumor-infiltrating CD8+ T lymphocytes are prognostic factors of human ovarian cancer. Proc Natl Acad Sci U S A 2007; 104:3360-5; PMID:17360651; http://dx.doi.org/10.1073/pnas.0611533104
4. C.Blank, T.F.Gajewski, A.Mackensen. Interaction of PD-L1 on tumor cells with PD-1 on tumor-specific T cells as a mechanism of immune evasion: implications for tumor immunotherapy. Cancer Immunol Immunother 2005; 54:307-14; PMID:15599732; http://dx.doi.org/10.1007/s00262-004-0593-x
5. M.E.Keir, M.J.Butte, G.J.Freeman, A.H.Sharpe. PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol 2008; 26:677-704; PMID:18173375; http://dx.doi.org/10.1146/annurev.immunol.26.021607.090331
6. C.Blank, A.Mackensen. Contribution of the PD-L1/PD-1 pathway to T-cell exhaustion: an update on implications for chronic infections and tumor evasion. Cancer Immunol Immunother 2007; 56:739-45; PMID:17195077; http://dx.doi.org/10.1007/s00262-006-0272-1
7. D.E.Dolan, S.Gupta. PD-1 pathway inhibitors: changing the landscape of cancer immunotherapy. Cancer Control 2014; 21:231-7; PMID:24955707.
8. D.S.Chen, B.A.Irving, F.S.Hodi. Molecular pathways: next-generation immunotherapy–inhibiting programmed death-ligand 1 and programmed death-1. Clin Cancer Res 2012; 18:6580-7; PMID:23087408; http://dx.doi.org/10.1158/1078-0432.CCR-12-1362
9. R.S.Herbst, M.S.Gordon, G.D.Fine, J.A.Sosman, J.Soria, O.Hamid, J.D.Powderly, H.A.Burris, A.Mokatrin, M.Kowanetz, et al. A study of MPDL3280A, an engineered PD-L1 antibody in patients with locally advanced or metastatic tumors. Journal of Clinical Oncology, 2013 ASCO Annual Meeting Abstracts. Vol 31: No 15_suppl (May 20 Supplement), 2013, 3000
10. R.S.Herbst, J.C.Soria, M.Kowanetz, G.D.Fine, O.Hamid, M.S.Gordon, J.A.Sosman, D.F.McDermott, J.D.Powderly, S.N.Gettinger, et al. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature 2014; 515:563-7; PMID:25428504; http://dx.doi.org/10.1038/nature14011
11. T.Powles, J.P.Eder, G.D.Fine, F.S.Braiteh, Y.Loriot, C.Cruz, J.Bellmunt, H.A.Burris, D.P.Petrylak, S.L.Teng, et al. MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer. Nature 2014; 515:558-62; PMID:25428503; http://dx.doi.org/10.1038/nature13904
12. N.Chirmule, V.Jawa, B.Meibohm. Immunogenicity to therapeutic proteins: impact on PK/PD and efficacy. AAPS J 2012; 14:296-302; PMID:22407289; http://dx.doi.org/10.1208/s12248-012-9340-y
13. I.Hotzel, F.P.Theil, L.J.Bernstein, S.Prabhu, R.Deng, L.Quintana, J.Lutman, R.Sibia, P.Chan, D.Bumbaca, et al. A strategy for risk mitigation of antibodies with fast clearance. mAbs 2012; 4:753-60; PMID:23778268; http://dx.doi.org/10.4161/mabs.22189
14. C.A.Boswell, D.Bumbaca, P.J.Fielder, L.A.Khawli. Compartmental tissue distribution of antibody therapeutics: experimental approaches and interpretations. AAPS J 2012; 14:612-8; PMID:22648903; http://dx.doi.org/10.1208/s12248-012-9374-1
15. P.L.Martin, P.J.Bugelski. Concordance of preclinical and clinical pharmacology and toxicology of monoclonal antibodies and fusion proteins: soluble targets. Br J Pharmacol 2012; 166:806-22; PMID:22168335; http://dx.doi.org/10.1111/j.1476-5381.2011.01812.x
16. P.J.Bugelski, P.L.Martin. Concordance of preclinical and clinical pharmacology and toxicology of therapeutic monoclonal antibodies and fusion proteins: cell surface targets. Br J Pharmacol 2012; 166:823-46; PMID:22168282; http://dx.doi.org/10.1111/j.1476-5381.2011.01811.x
17. D.Fairman, R.Narwal, M.Liang, P.B.Robbins, A.Schneider, C.Chavez, H.Lu, M.Pak, A.Blake-Haskins, J.Vasselli, et al. Pharmacokinetics of MEDI4736, a fully human anti-PDL1 monoclonal antibody, in patients with advanced solid tumors. Journal of Clinical Oncology, 2014 ASCO Annual Meeting Abstracts. Vol 32: No 15_suppl (May 20 Supplement), 2014: 2602
18. X.Song, M.Pak, C.Chavez, M.Liang, H.Lu, M.Schwickart, J.A.Blake-Haskins, P.B.Robbins, X.Jin, A.K.Gupta, et al. Pharmacokinetics and pharmacodynamics of MEDI4736, a fully human antiprogrammed death ligand 1 (PD-L1) monoclonal antibody, in patients with advanced solid tumors. J Clin Oncol 2015; 33; http://dx.doi.org/10.1200/JCO.2015.61.2408
19. J.R.Brahmer, C.G.Drake, I.Wollner, J.D.Powderly, J.Picus, W.H.Sharfman, E.Stankevich, A.Pons, T.M.Salay, T.L.McMiller, et al. Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates. J Clin Oncol 2010; 28:3167-75; PMID:20516446; http://dx.doi.org/10.1200/JCO.2009.26.7609
20. D.Bumbaca, H.Xiang, C.A.Boswell, R.E.Port, S.L.Stainton, E.E.Mundo, S.Ulufatu, A.Bagri, F.P.Theil, P.J.Fielder, et al. Maximizing tumour exposure to anti-neuropilin-1 antibody requires saturation of non-tumour tissue antigenic sinks in mice. Br J Pharmacol 2012; 166:368-77; PMID:22074316; http://dx.doi.org/10.1111/j.1476-5381.2011.01777.x
21. B.A.Irving. Optimizing the Therapeutic Potential of PD-L1 Blockade as a Single Agent and Through Combination Therapy. SITC 27th Annual Meeting Bethesda North Marriott Hotel & Conference Center, North Bethesda, MD, 2012.
22. K.Fujimori, D.G.Covell, J.E.Fletcher, J.N.Weinstein. Modeling analysis of the global and microscopic distribution of immunoglobulin G, F(ab')2, and Fab in tumors. Cancer Res 1989; 49:5656-63; PMID:2790783
23. J.K.Peterson, P.J.Houghton. Integrating pharmacology and in vivo cancer models in preclinical and clinical drug development. Eur J Cancer 2004; 40:837-44; PMID:15120039; http://dx.doi.org/10.1016/j.ejca.2004.01.003
24. H.Wong, E.F.Choo, B.Alicke, X.Ding, H.La, E.McNamara, F.P.Theil, J.Tibbitts, L.S.Friedman, C.E.Hop, et al. Antitumor activity of targeted and cytotoxic agents in murine subcutaneous tumor models correlates with clinical response. Clin Cancer Res 2012; 18:3846-55; PMID:22648270; http://dx.doi.org/10.1158/1078-0432.CCR-12-0738
25. W.K.Bleeker, M.E.Munk, W.J.Mackus, J.H.van den Brakel, M.Pluyter, M.J.Glennie, J.G.Van De Winkel, P.W.Parren. Estimation of dose requirements for sustained in vivo activity of a therapeutic human anti-CD20 antibody. Br J Haematol 2008; 140:303-12; PMID:18045353; http://dx.doi.org/10.1111/j.1365-2141.2007.06916.x
26. F.R.Luo, Z.Yang, H.Dong, A.Camuso, K.McGlinchey, K.Fager, C.Flefleh, D.Kan, I.Inigo, S.Castaneda, et al. Correlation of pharmacokinetics with the antitumor activity of Cetuximab in nude mice bearing the GEO human colon carcinoma xenograft. Cancer Chemother Pharmacol 2005; 56:455-64; PMID:15947929; http://dx.doi.org/10.1007/s00280-005-1022-3
27. C.V.Pastuskovas, E.E.Mundo, S.P.Williams, T.K.Nayak, J.Ho, S.Ulufatu, S.Clark, S.Ross, E.Cheng, K.Parsons-Reponte, et al. Effects of anti-VEGF on pharmacokinetics, biodistribution, and tumor penetration of trastuzumab in a preclinical breast cancer model. Mol Cancer Ther 2012; 11:752-62; PMID:22222630; http://dx.doi.org/10.1158/1535-7163.MCT-11-0742-T
28. R.Chizzonite, T.Truitt, F.J.Podlaski, A.G.Wolitzky, P.M.Quinn, P.Nunes, A.S.Stern, M.K.Gately. IL-12: monoclonal antibodies specific for the 40-kDa subunit block receptor binding and biologic activity on activated human lymphoblasts. J Immunol 1991; 147:1548-56; PMID:1715362
29. C.V.Pastuskovas, W.Mallet, S.Clark, M.Kenrick, M.Majidy, M.Schweiger, M.Van Hoy, S.P.Tsai, G.Bennett, B.Q.Shen, et al. Effect of immune complex formation on the distribution of a novel antibody to the ovarian tumor antigen CA125. Drug Metab Dispos 2010; 38:2309-19; PMID:20823292; http://dx.doi.org/10.1124/dmd.110.034330
30. C.A.Boswell, G.Z.Ferl, E.E.Mundo, M.G.Schweiger, J.Marik, M.P.Reich, F.P.Theil, P.J.Fielder, L.A.Khawli. Development and evaluation of a novel method for preclinical measurement of tissue vascular volume. Mol Pharm 2010; 7:1848-57; PMID:20704296; http://dx.doi.org/10.1021/mp100183k
31. C.A.Boswell, G.Z.Ferl, E.E.Mundo, D.Bumbaca, M.G.Schweiger, F.P.Theil, P.J.Fielder, L.A.Khawli. Effects of anti-VEGF on predicted antibody biodistribution: roles of vascular volume, interstitial volume, and blood flow. PLoS One 2011; 6:e17874; PMID:21436893; http://dx.doi.org/10.1371/journal.pone.0017874