First-in-human study of the antibody DR5 agonist DS-8273a in patients with advanced solid tumors

Investigational New Drugs

Volumn 35, Issue 3, 2017, Pages 298-306

  Forero, Andres ^a   Bendell, Johanna C ^b   Kumar, Prasanna ^c   Janisch, Linda ^d   Rosen, Michael ^c   Wang, Qiang ^c   Copigneaux, Catherine ^c   Desai, Madhuri ^c,e   Senaldi, Giorgio ^c   Maitland, Michael L ^d,f  

^a University of Alabama at Birmingham   (United States)

^b SARAH CANNON RESEARCH INSTITUTE   (United States)

^c DAIICHI SANKYO INC   (United States)

^d UNIVERSITY OF CHICAGO   (United States)

^e ELI LILLY AND COMPANY   (United States)

^f Inova Schar Cancer Institute   (United States)

Author keywords

Apoptosis; DR5; DS 8273a; Myeloid derived suppressor cells; Pharmacokinetics; Phase 1

Indexed keywords

BILIRUBIN; DS 8273A; MONOCLONAL ANTIBODY; UNCLASSIFIED DRUG; ANTINEOPLASTIC AGENT; TNFRSF10B PROTEIN, HUMAN; TUMOR NECROSIS FACTOR RELATED APOPTOSIS INDUCING LIGAND RECEPTOR;

ABDOMINAL PAIN; ADULT; ADVANCED CANCER; AGED; AREA UNDER THE CURVE; ARTHRALGIA; ARTICLE; ASCITES; BACKACHE; BILIRUBIN BLOOD LEVEL; BREAST CANCER; CANCER RADIOTHERAPY; CLINICAL ARTICLE; COLORECTAL CANCER; CONFUSION; CONSTIPATION; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DECREASED APPETITE; DIARRHEA; DOSE RESPONSE; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG ELIMINATION; DRUG EXPOSURE; DRUG HALF LIFE; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; DYSPNEA; FATIGUE; FEMALE; HEAD AND NECK CANCER; HUMAN; HUMAN TISSUE; LIVER CANCER; MALE; MAXIMUM PLASMA CONCENTRATION; MAXIMUM TOLERATED DOSE; MELANOMA; MINIMUM PLASMA CONCENTRATION; MULTICENTER STUDY; MULTIPLE CYCLE TREATMENT; MYELOID-DERIVED SUPPRESSOR CELL; NAUSEA; OPEN STUDY; OVARY CANCER; PANCREAS CANCER; PERIPHERAL EDEMA; PHARMACODYNAMICS; PHASE 1 CLINICAL TRIAL; QT INTERVAL; SARCOMA; SIDE EFFECT; SOLID MALIGNANT NEOPLASM; STEADY STATE; TIME TO MAXIMUM PLASMA CONCENTRATION; URINARY TRACT INFECTION; VOMITING; AGONISTS; CELL COUNT; CHEMICALLY INDUCED; CLINICAL TRIAL; DRUG EFFECTS; METABOLISM; MIDDLE AGED; NEOPLASM;

ADULT; AGED; ANTIBODIES, MONOCLONAL; ANTINEOPLASTIC AGENTS; CELL COUNT; DIARRHEA; FATIGUE; FEMALE; HUMANS; MALE; MAXIMUM TOLERATED DOSE; MIDDLE AGED; MYELOID-DERIVED SUPPRESSOR CELLS; NAUSEA; NEOPLASMS; RECEPTORS, TNF-RELATED APOPTOSIS-INDUCING LIGAND; VOMITING;

EID: 85008172923     PISSN: 01676997     EISSN: 15730646     Source Type: Journal    
DOI: 10.1007/s10637-016-0420-1     Document Type: Article

References (20)

1. Rowinsky EK (2005) Targeted induction of apoptosis in cancer management: the emerging role of tumor necrosis factor-related apoptosis-inducing ligand receptor activating agents. J Clin Oncol 23:9394
2. Takeda K, Stagg J, Yagita H, Okumura K, Smyth MJ (2007) Targeting death-inducing receptors in cancer therapy. Oncogene 26(25):3745–3757
3. Debatin KM, Krammer PH (2004) Death receptors in chemotherapy and cancer. Oncogene 23(16):2950–2966
4. Daniels RA, Turley H, Kimberley FC, Liu XS, Mongkolsapaya J, Ch'En P, Xu XN, Jin BQ, Pezzella F, Screaton GR (2005) Expression of TRAIL and TRAIL receptors in normal and malignant tissues. Cell Res 15(6):430–438
5. Ashkenazi A, Pai RC, Fong S, Leung S, Lawrence DA, Marsters SA, Blackie C, Chang L, AE MM, Hebert A, DeForge L, Koumenis IL, Lewis D, Harris L, Bussiere J, Koeppen H, Shahrokh Z, Schwall RH (1999) Safety and antitumor activity of recombinant soluble Apo2 ligand. J Clin Invest 104(2):155–162
6. Ashkenazi A (2002) Targeting death and decoy receptors of the tumour-necrosis factor superfamily. Nat Rev Cancer 2(6):420–430
7. Walczak H, Degli-Esposti MA, Johnson RS, Smolak PJ, Waugh JY, Boiani N, Timour MS, Gerhart MJ, Schooley KA, Smith CA, Goodwin RG, Rauch CT (1997) TRAIL-R2: a novel apoptosis-mediating receptor for TRAIL. EMBO J 16(17):5386–5397
8. Hotte SJ, Hirte HW, Chen EX, Siu LL, Le LH, Corey A, Iacobucci A, MacLean M, Lo L, Fox NL, Oza AM (2008) A phase 1 study of mapatumumab (fully human monoclonal antibody to TRAIL-R1) in patients with advanced solid malignancies. Clin Cancer Res 14(11):3450–3455
9. Herbst RS, Kurzrock R, Hong DS, Valdivieso M, Hsu CP, Goyal L, Juan G, Hwang YC, Wong S, Hill JS, Friberg G, LoRusso PM (2010) A first­in­human study of conatumumab in adult patients with advanced solid tumors. Clin Cancer Res 16(23):5883–5891
10. Forero-Torres A, Shah J, Wood T, Posey J, Carlisle R, Copigneaux C, Luo FR, Wojtowicz-Praga S, Percent I, Saleh M (2010) Phase I trial of weekly tigatuzumab, an agonistic humanized monoclonal antibody targeting death receptor 5 (DR5). Cancer Biother Radiopharm 25(1):13–19
11. Plummer R, Attard G, Pacey S, Li L, Razak A, Perrett R, Barrett M, Judson I, Kaye S, Fox NL, Halpern W, Corey A, Calvert H, de Bono J (2007) Phase 1 and pharmacokinetic study of lexatumumab in patients with advanced cancers. Clin Cancer Res 13(20):6187–6194
12. Wakelee HA, Patnaik A, Sikic BI, Mita M, Fox NL, Miceli R, Ullrich SJ, Fisher GA, Tolcher AW (2010) Phase I and pharmacokinetic study of lexatumumab (HGS-ETR2) given every 2 weeks in patients with advanced solid tumors. Ann Oncol 21(2):376–381
13. Sharma S, de Vries EG, Infante JR, Oldenhuis CN, Gietema JA, Yang L, Bilic S, Parker K, Goldbrunner M, Scott JW, Burris HA 3rd (2014) Safety, pharmacokinetics, and pharmacodynamics of the DR5 antibody LBY135 alone and in combination with capecitabine in patients with advanced solid tumors. Investig New Drugs 32(1):135–144
14. Forero-Torres A, Infante JR, Waterhouse D, Wong L, Vickers S, Arrowsmith E, He AR, Hart L, Trent D, Wade J, Jin X, Wang Q, Austin T, Rosen M, Beckman R, von Roemeling R, Greenberg J, Saleh M (2013) Phase 2, multicenter, open-label study of tigatuzumab (CS-1008), a humanized monoclonal antibody targeting death receptor 5, in combination with gemcitabine in chemotherapy-naive patients with unresectable or metastatic pancreatic cancer. Cancer Med 2(6):925–932
15. Lim B, Allen JE, Prabhu VV, Talekar MK, Finnberg NK, El-Deiry WS (2015) Targeting TRAIL in the treatment of cancer: new developments. Expert Opin Ther Targets 19(9):1171–1185
16. Burvenich IJ, Lee FT, Guo N, Gan HK, Rigopoulos A, Parslow AC, O'Keefe GJ, Gong SJ, Tochon-Danguy H, Rudd SE, Donnelly PS, Kotsuma M, Ohtsuka T, Senaldi G, Scott AM (2016) In vitro and in vivo evaluation of 89Zr-DS-8273a as a Theranostic for anti-death receptor 5 therapy. Theranostics 6(12):2225–2234
17. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45(2):228–247
18. Condamine T, Kumar V, Ramachandran IR, Youn JI, Celis E, Finnberg N, El-Deiry WS, Winograd R, Vonderheide RH, English NR, Knight SC, Yagita H, McCaffrey JC, Antonia S, Hockstein N, Witt R, Masters G, Bauer T, Gabrilovich DI (2014) ER stress regulates myeloid-derived suppressor cell fate through TRAIL-R-mediated apoptosis. J Clin Invest 124(6):2626–2639
19. Gabrilovich DI, Ostrand-Rosenberg S, Bronte V (2012) Coordinated regulation of myeloid cells by tumours. Nat Rev Immunol 12(4):253–268
20. Dominquez G, Condamine TC, Mony S, Hashimoto A, Wang F, Liu Q, Forero A, Bendell JC, Witt R, Hockstein N, Kumar P, Gabrilovich D (2016) Selective targeting of myeloid-derived suppressor cells in cancer patients using DS-8273a, an agonistic TRAIL-R2 antibody Clin Cancer Res (epub ahead of print, PMID:27965309)