Unexpected hepatotoxicity in a phase I study of TAS266, a novel tetravalent agonistic Nanobody® targeting the DR5 receptor

Cancer Chemotherapy and Pharmacology

Volumn 75, Issue 5, 2015, Pages 887-895

  Papadopoulos, Kyriakos P ^a   Isaacs, Randi ^b   Bilic, Sanela ^b   Kentsch, Kerstin ^b   Huet, Heather A ^c   Hofmann, Matthias ^b   Rasco, Drew ^a   Kundamal, Nicole ^b   Tang, Zhongwhen ^b   Cooksey, Jennifer ^d   Mahipal, Amit ^d  

^a South Texas Accelerated Research Therapeutics   (United States)

^b NOVARTIS PHARMA AG   (Switzerland)

^c NOVARTIS INSTITUTES FOR BIOMEDICAL RESEARCH   (United States)

^d H LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE   (United States)

Author keywords

DR5 receptor; Hepatotoxicity; Immunogenicity; Nanobody ; TAS266

Indexed keywords

NANOBODY; TUMOR NECROSIS FACTOR RELATED APOPTOSIS INDUCING LIGAND RECEPTOR;

AGED; BLOOD; CLINICAL TRIAL; COHORT ANALYSIS; DOSE RESPONSE; DRUG-INDUCED LIVER INJURY; HUMAN; IMMUNOLOGY; INTRAVENOUS DRUG ADMINISTRATION; MIDDLE AGED; NEOPLASMS; PHASE 1 CLINICAL TRIAL;

AGED; COHORT STUDIES; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG-INDUCED LIVER INJURY; HUMANS; INFUSIONS, INTRAVENOUS; MIDDLE AGED; NEOPLASMS; RECEPTORS, TNF-RELATED APOPTOSIS-INDUCING LIGAND; SINGLE-DOMAIN ANTIBODIES;

EID: 84938677829     PISSN: 03445704     EISSN: 14320843     Source Type: Journal    
DOI: 10.1007/s00280-015-2712-0     Document Type: Article

References (36)

1. Ghobrial IM, Witzig TE, Adjei AA (2005) Targeting apoptosis pathways in cancer therapy. CA Cancer J Clin 55:178-194
2. Ashkenazi A (2002) Targeting death and decoy receptors or the tumor-necrosis factor superfamily. Nat Rev Cancer 2:420-430
3. Pan G, O'Rourke K, Chinnaiyan AM et al (1997) The receptor for the cytotoxic ligand TRAIL. Science 276:111-113
4. Roth W, Isenmann S, Naumann U et al (1999) Locoregional Apo2L/TRAIL eradicates intracranial human malignant glioma xenografts in athymic mice in the absence of neurotoxicity. Biochem Biophys Res Commun 265:479-483
5. Mitsiades CS, Treon SP, Mitsiades N et al (2001) TRAIL/Apo2L ligand selectively induces apoptosis and overcomes drug resistance in multiple myeloma: therapeutic applications. Blood 98:795-804
6. Ashkenazi A, Pai RC, Fong S et al (1999) Safety and antitumor activity of recombinant soluble Apo2 ligand. J Clin Invest 104:155-162
7. Duiker WE, Mom CH, de Jong S et al (2006) The clinical of TRAIL. Eur J Cancer 42:2233-2240
8. Oikonomou E, Pintzas A (2013) The TRAIL of oncogenes to apoptosis. Biofactors 39:343-354
9. Gonzalvez F, Ashkenazi A (2010) New insights into apoptosis signaling by Apo2L/TRAIL. Oncogene 29:4752-4765
10. Alamasan A, Ashkenazi A (2003) Apo2L/TRAIL: apoptosis signaling, biology, and potential for cancer therapy. Cytokine Growth Factor Rev 14:337-348
11. Soria JC, Márk Z, Zaltoukal P et al (2011) Randomized phase II study of dulanermin in combination with paclitaxel, carboplatin, and bevacizumab in advanced non-small-cell lung cancer. J Clin Oncol 29:4442-4451
12. Wakelee HA, Patnaik A, Sikic BI et al (2010) Phase I and pharmacokinetic study of lexatumumab (HGS-ETR2) given every 2 weeks in patients with advanced solid tumors. Ann Oncol 21:376-381
13. Sharma S, de Vries EG, Infante JR et al (2014) Safety, pharmacokinetics, and pharmacodynamics of the DR5 antibody LBY135 alone an in combination with capecitabine in patients with advanced solid tumors. Invest New Drugs 32:135-144
14. Forero-Torres A, Shah J, Wood T et al (2010) Phase I trial of weekly tigatuzumab, an agonistic humanized monoclonal antibody targeting death receptor 5 (DR5). Cancer Biother Radiopharm 25:13-19
15. Paz-Ares L, Bálint B, de Boer RH et al (2013) A randomized phase 2 study of paclitaxel and carboplatin with or without conatumumab for first-line treatment of advanced non-small-cell lung cancer. J Thorac Oncol 8:329-337
16. Rocha Lima CM, Bayraktar S, Flores AM et al (2012) Phase Ib study of drozitumab combined with first-line mFOLFOX plus bevacizumab in patients with metastatic colorectal cancer. Cancer Invest 30:727-731
17. Huet HA, Growney JD, Johnson JA et al (2014) Multivalent nanobodies targeting death receptor 5 elicit superior tumor cell killing through efficient caspase induction. MAbs 6:1560-1570
18. Hao C, Song JH, His B et al (2004) TRAIL inhibits tumor growth but is nontoxic to human hepatocytes in chimeric mice. Cancer Res 64:8502-8506
19. H domain antibody antagonist of TNF-α receptor 1. J Clin Immunol 33:1192-1203
20. Xue L, Rup B (2013) Evaluation of pre-existing antibody presence as a risk factor for posttreatment anti-drug antibody induction: analysis of human clinical study data for multiple biotherapeutics. AAPS J 15:893-896
21. Xue L, Fiscella M, Rajadhyaksha M et al (2013) Pre-existing biotherapeutic-reactive antibodies: survey results within the American Association of Pharmaceutical Scientists. AAPS J 15:852-855
22. Neuenschwander B, Branson M, Gsponer T (2008) Critical aspects of the Bayesian approach to phase I cancer trials. Stat Med 27:2420-2439
23. Jo M, Kim TH, Seol DW et al (2000) Apoptosis induced in normal human hepatocytes by tumor necrosis factor-related apoptosis-inducing ligand. Nat Med 6:564-567
24. Volkmann X, Fischer U, Bahr MJ et al (2007) Increased hepatotoxicity of tumor necrosis factor-related apoptosis-inducing ligand in diseased human liver. Hepatology 46:1498-1508
25. Plummer R, Attard G, Pacey S et al (2007) Phase 1 and pharmacokinetic study of lexatumumab in patients with advanced cancers. Clin Cancer Res 13:6187-6194
26. Camidge DR, Herbst RS, Gordon MS et al (2010) A phase I safety and pharmacokinetic study of the death receptor 5 agonistic antibody PRO95780 in patients with advanced malignancies. Clin Cancer Res 16:1256-1263
27. Demetri GD, Le Cesne A, Chawla SP et al (2012) First-line treatment of metastatic or locally advanced unresectable soft tissue sarcomas with conatumumab in combination with doxorubicin or doxorubicin alone: a phase I/II open-label and double-blind study. Eur J Cancer 48:547-563
28. Herbst RS, Eckhardt SG, Kurzrock R et al (2010) Phase I dose-escalation study of recombinant human Apo2L/TRAIL, a dual proapoptotic receptor agonist, in patients with advanced cancer. J Clin Oncol 28:2839-2846
29. Bartunek J, Barbato E, Heyndrickx G et al (2013) Novel antiplatelet agents: ALX-0081, a Nanobody directed towards von Willebrand factor. J Cardiovasc Transl Res 6:363-366
30. ® (ALX-0061) resulted in 84% ACR20 improvement and 58% DAS28 remission in a phase I/II study in RA. Ann Rheum Dis 72(suppl 3):64
31. Schoen P, Jacobs S, Verschueren K et al (2013) Anti-RANKL Nanobody ALX-0141 shows sustained biomarker inhibition in a phase I study in healthy postmenopausal women. Bone Abstr. doi: 10.1530/boneabs.1.PP135
32. Fleischmann Roy M, Bruyn De et al (2012) A novel individualized treatment approach in open-label extension study of ozoralizumab (ATN-103) in subjects with rheumatoid arthritis on a background of methotrexate. Arthritis Rheum 64(Suppl 10):1311
33. Corazza N, Kassahn D, Jakob S et al (2009) TRAIL-induced apoptosis: between tumor therapy and immunopathology. Ann N Y Acad Sci 1171:50-58
34. Mundt B, Wirth T, Zender L et al (2005) Tumour necrosis factor related apoptosis inducing ligand (TRAIL) induces hepatic steatosis in viral hepatitis and after alcohol intake. Gut 54:1590-1596
35. Pilgrim CH, Thomson BN, Banting S et al (2012) The developing clinical problem of chemotherapy-induced hepatic injury. ANZ J Surg 82:23-29
36. Ryan P, Nanji S, Pollett A et al (2010) Chemotherapy-induced liver injury in metastatic colorectal cancer: semiquantitative histologic analysis of 334 resected liver specimens shows that vascular injury but not steatohepatitis is associated with preoperative chemotherapy. Am J Surg Pathol 34:784-791