Preclinical analyses and phase I evaluation of LY2603618 administered in combination with pemetrexed and cisplatin in patients with advanced cancer

Investigational New Drugs

Volumn 32, Issue 5, 2014, Pages 955-968

  Calvo, Emiliano ^a   Chen, Victor J ^b   Marshall, Mark ^b   Ohnmacht, Ute ^b   Hynes, Scott M ^b   Kumm, Elizabeth ^c   Diaz, H Bruce ^b   Barnard, Darlene ^b   Merzoug, Farhana F ^b   Huber, Lysiane ^b   Kays, Lisa ^b   Iversen, Philip ^b   Calles, Antonio ^a,d   Voss, Beatrice ^e   Lin, Aimee Bence ^b   Dickgreber, Nicolas ^f   Wehler, Thomas ^e   Sebastian, Martin ^g  

^a Hospital Madrid Norte Sanchinarro   (Spain)

^b ELI LILLY AND COMPANY   (United States)

^c SYNEOS HEALTH   (United States)

^d Structural Biology and Biocomputing Programme   (Spain)

^e JOHANNES GUTENBERG UNIVERSITY   (Germany)

^f Department of Respiratory Medicine and Thoracic Oncology Mathias Spital Rheine ^*  (Germany)

^g GOETHE UNIVERSITY   (Germany)

Author keywords

Cancer; Cell cycle; CHK1; Lung cancer; LY2603618; Pharmacokinetics

Indexed keywords

ANTINEOPLASTIC AGENT; CARBANILAMIDE DERIVATIVE; CISPLATIN; DNA; GLUTAMIC ACID DERIVATIVE; GUANINE; PEMETREXED; PYRAZINE DERIVATIVE; RABUSERTIB;

ADULT; AGED; ANALOGS AND DERIVATIVES; ANIMAL; BLOOD; CLINICAL TRIAL; CONTROLLED STUDY; DRUG EFFECTS; DRUG SCREENING; FEMALE; HUMAN; MALE; METABOLISM; MIDDLE AGED; MULTICENTER STUDY; NEOPLASMS; NUDE MOUSE; PATHOLOGY; PHASE 1 CLINICAL TRIAL; PHASE 2 CLINICAL TRIAL; RANDOMIZED CONTROLLED TRIAL; TUMOR CELL LINE; TUMOR VOLUME;

ADULT; AGED; ANIMALS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; CELL LINE, TUMOR; CISPLATIN; DNA; FEMALE; GLUTAMATES; GUANINE; HUMANS; MALE; MICE, NUDE; MIDDLE AGED; NEOPLASMS; PHENYLUREA COMPOUNDS; PYRAZINES; TUMOR BURDEN; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84930709901     PISSN: 01676997     EISSN: 15730646     Source Type: Journal    
DOI: 10.1007/s10637-014-0114-5     Document Type: Review

References (37)

1. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM (2010) Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 127(12):2893-2917
2. Yang P, Allen MS, Aubry MC, Wampfler JA, Marks RS, Edell ES, Thibodeau S, Adjei AA, Jett J, Deschamps C (2005) Clinical features of 5,628 primary lung cancer patients: experience at Mayo Clinic from 1997 to 2003. Chest 128(1):452-462
3. Paz-Ares L, de Marinis F, Dediu M, Thomas M, Pujol JL, Bidoli P, Molinier O, Sahoo TP, Laack E, Reck M, Corral J, Melemed S, John W, Chouaki N, Zimmermann AH, Visseren-Grul C, Gridelli C (2012) Maintenance therapy with pemetrexed plus best supportive care versus placebo plus best supportive care after induction therapy with pemetrexed plus cisplatin for advanced non-squamous non-small-cell lung cancer (PARAMOUNT): a double-blind, phase 3, randomised controlled trial. Lancet Oncol 13(3):247-255
4. Scagliotti GV, Parikh P, von Pawel J, Biesma B, Vansteenkiste J, Manegold C, Serwatowski P, Gatzemeier U, Digumarti R, Zukin M, Lee JS, Mellemgaard A, Park K, Patil S, Rolski J, Goksel T, de Marinis F, Simms L, Sugarman KP, Gandara D (2008) Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clini Oncol 26(21):3543-3551
5. Manegold C, Gatzemeier U, von Pawel J, Pirker R, Malayeri R, Blatter J, Krejcy K (2000) Front-line treatment of advanced non-small-cell lung cancer with MTA (LY231514, pemetrexed disodium, ALIMTA) and cisplatin: a multicenter phase II trial. Annals of Oncol 11(4):435-440
6. Shepherd FA, Dancey J, Arnold A, Neville A, Rusthoven J, Johnson RD, Fisher B, Eisenhauer E (2001) Phase II study of Pemetrexed disodium, a multitargeted antifolate, and cisplatin as first-line therapy in patients with advanced nonsmall cell lung carcinoma: a study of the national cancer institute of Canada clinical trials group. Cancer 92(3):595-600
7. Sanchez Y, Wong C, Thoma RS, Richman R, Wu Z, Piwnica-Worms H, Elledge SJ (1997) Conservation of the Chk1 checkpoint pathway in mammals: linkage of DNA damage to Cdk regulation through Cdc25. Science 277(5331):1497-1501
8. Karnitz LM, Flatten KS, Wagner JM, Loegering D, Hackbarth JS, Arlander SJ, Vroman BT, Thomas MB, Baek YU, Hopkins KM, Lieberman HB, Chen J, Cliby WA, Kaufmann SH (2005) Gemcitabine-induced activation of checkpoint signaling pathways that affect tumor cell survival. Mol Pharmacol 68(6): 1636-1644
9. Liu Q, Guntuku S, Cui XS, Matsuoka S, Cortez D, Tamai K, Luo G, Carattini-Rivera S, DeMayo F, Bradley A, Donehower LA, Elledge SJ (2000) Chk1 is an essential kinase that is regulated by Atr and required for the G(2)/M DNA damage checkpoint. Genes Dev 14(12):1448-1459
10. Morgan MA, Parsels LA, Parsels JD, Mesiwala AK, Maybaum J, Lawrence TS (2005) Role of checkpoint kinase 1 in preventing premature mitosis in response to gemcitabine. Cancer Res 65(15): 6835-6842
11. Zhao H, Watkins JL, Piwnica-Worms H (2002) Disruption of the checkpoint kinase 1/cell division cycle 25A pathway abrogates ionizing radiation-induced S and G2 checkpoints. Proc Natl Acad Sci U S A 99(23):14795-14800
12. Merry C, Fu K, Wang J, Yeh IJ, Zhang Y (2010) Targeting the checkpoint kinase Chk1 in cancer therapy. Cell Cycle 9(2):279-283
13. Tse AN, Carvajal R, Schwartz GK (2007) Targeting checkpoint kinase 1 in cancer therapeutics. Clin Cancer Res 13(7):1955-1960
14. Xiao Z, Xue J, Sowin TJ, Rosenberg SH, Zhang H (2005) A novel mechanism of checkpoint abrogation conferred by Chk1 downregulation. Oncogene 24(8):1403-1411
15. Kortmansky J, Shah MA, Kaubisch A, Weyerbacher A, Yi S, Tong W, Sowers R, Gonen M, O'Reilly E, Kemeny N, Ilson DI, Saltz LB, Maki RG, Kelsen DP, Schwartz GK (2005) Phase I trial of the cyclin-dependent kinase inhibitor and protein kinase C inhibitor 7- hydroxystaurosporine in combination with Fluorouracil in patients with advanced solid tumors. J Clin Oncol 23(9):1875-1884
16. Lara PN Jr, Mack PC, Synold T, Frankel P, Longmate J, Gumerlock PH, Doroshow JH, Gandara DR (2005) The cyclin-dependent kinase inhibitor UCN-01 plus cisplatin in advanced solid tumors: a California cancer consortium phase I pharmacokinetic and molecular correlative trial. Clin Cancer Res 11(12):4444-4450
17. Blasina A, Hallin J, Chen E, Arango ME, Kraynov E, Register J, Grant S, Ninkovic S, Chen P, Nichols T, O'Connor P, Anderes K (2008) Breaching the DNA damage checkpoint via PF-00477736, a novel small-molecule inhibitor of checkpoint kinase 1. Mol Cancer Ther 7(8):2394-2404
18. Janetka JW, Ashwell S, Zabludoff S, Lyne P (2007) Inhibitors of checkpoint kinases: from discovery to the clinic. Curr Opin Drug Discov Devel 10(4):473-486
19. Matthews DJ, Yakes FM, Chen J, Tadano M, Bornheim L, Clary DO, Tai A, Wagner JM, Miller N, Kim YD, Robertson S, Murray L, Karnitz LM (2007) Pharmacological abrogation of S-phase checkpoint enhances the anti-tumor activity of gemcitabine in vivo. Cell Cycle 6(1):104-110
20. Morgan MA, Parsels LA, Zhao L, Parsels JD, Davis MA, Hassan MC, Arumugarajah S, Hylander-Gans L, Morosini D, Simeone DM, Canman CE, Normolle DP, Zabludoff SD, Maybaum J, Lawrence TS (2010) Mechanism of radiosensitization by the Chk1/2 inhibitor AZD7762 involves abrogation of the G2 checkpoint and inhibition of homologous recombinational DNA repair. Cancer Res 70(12): 4972-4981
21. Tse AN, Rendahl KG, Sheikh T, Cheema H, Aardalen K, Embry M, Ma S, Moler EJ, Ni ZJ, Lopes de Menezes DE, Hibner B, Gesner TG, Schwartz GK (2007) CHIR-124, a novel potent inhibitor of Chk1, potentiates the cytotoxicity of topoisomerase I poisons in vitro and in vivo. Clini Cancer Res 13(2 Pt 1):591-602
22. Walton MI, Eve PD, Hayes A, Valenti M, De Haven BA, Box G, Boxall KJ, Aherne GW, Eccles SA, Raynaud FI, Williams DH, Reader JC, Collins I, Garrett MD (2010) The preclinical pharmacology and therapeutic activity of the novel CHK1 inhibitor SAR- 020106. Mol Cancer Ther 9(1):89-100
23. Zabludoff SD, Deng C, Grondine MR, Sheehy AM, Ashwell S, Caleb BL, Green S, Haye HR, Horn CL, Janetka JW, Liu D, Mouchet E, Ready S, Rosenthal JL, Queva C, Schwartz GK, Taylor KJ, Tse AN, Walker GE, White AM (2008) AZD7762, a novel checkpoint kinase inhibitor, drives checkpoint abrogation and potentiates DNA-targeted therapies. Mol Cancer Ther 7(9):2955-2966
24. Wagner JM, Karnitz LM (2009) Cisplatin-induced DNA damage activates replication checkpoint signaling components that differentially affect tumor cell survival. Mol Pharmacol 76(1): 208-214
25. Bartucci M, Svensson S, Romania P, Dattilo R, Patrizii M, Signore M, Navarra S, Lotti F, Biffoni M, Pilozzi E, Duranti E, Martinelli S, Rinaldo C, Zeuner A, Maugeri-Sacca M, Eramo A, De Maria R (2012) Therapeutic targeting of Chk1 in NSCLC stem cells during chemotherapy. Cell Death Differ 19(5):768-778
26. Gadhikar MA, Sciuto MR, Ortega Alves MV, Pickering CR, Osman AA, Neskey DM, Zhao M, Fitzgerald AL, Myers JN, Frederick MJ (2013) Chk1/2 inhibition overcomes the cisplatin resistance of head and neck cancer cells secondary to the loss of functional p53. Mol Cancer Ther 12(9):1860-1873
27. Min SH, Goldman ID, Zhao R (2008) Caffeine markedly sensitizes human mesothelioma cell lines to pemetrexed. Cancer Chemother Pharmacol 61(5):819-827
28. Stark GR, Taylor WR (2006) Control of the G2/M transition. Mol Biotechnol 32(3):227-248
29. King C, Diaz H, Barnard D, Barda D, Clawson D, Blosser W, Cox K, Guo S, Marshall M (2013) Characterization and preclinical development of LY2603618: a selective and potent Chk1 inhibitor. Investigational New Drugs
30. Marshall M, Barda D, Barnard D, Cox K, Diaz HB, King C, Nutter S, Westin E (2009) Characterization and preclinical development of LCI-1, a selective and potent Chk1 inhibitor in phase 1 clinical trials. Mol Cancer Ther (presented) 8 (B248)
31. Weiss GJ, Donehower RC, Iyengar T, Ramanathan RK, Lewandowski K, Westin E, Hurt K, Hynes SM, Anthony SP, McKane S (2013) Phase I dose-escalation study to examine the safety and tolerability of LY2603618, a checkpoint 1 kinase inhibitor, administered 1 day after pemetrexed 500 mg/m(2) every 21 days in patients with cancer. Investig New Drugs 31(1):136-144
32. Cristy M, Eckerman K (1987) Specific absorbed fractions of energy at various ages frominternal photon sources. I. Methods. ORNL/TM-8381 V 1:1987
33. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG (2000) New guidelines to evaluate the response to treatment in solid tumors. European organization for research and treatment of cancer, national cancer institute of the united states, national cancer institute of Canada. J Natl Cancer Inst 92(3):205-216
34. Rollins KD, Lindley C (2005) Pemetrexed: amultitargeted antifolate. Clin Ther 27(9):1343-1382
35. Chen VJ, Bewley JR, Andis SL, Schultz RM, Iversen PW, Shih C, Mendelsohn LG, Seitz DE, Tonkinson JL (1998) Preclinical cellular pharmacology of LY231514 (MTA): a comparison with methotrexate, LY309887 and raltitrexed for their effects on intracellular folate and nucleoside triphosphate pools in CCRF-CEM cells. Br J Cancer 78(Suppl 3):27-34
36. Nottebrock H, Then R (1977) Thymidine concentrations in serum and urine of different animal species and man. Biochem Pharmacol 26(22):2175-2179
37. Raghunathan K, Schmitz JC, Priest DG (1997) Impact of schedule on leucovorin potentiation of fluorouracil antitumor activity in dietary folic acid deplete mice. Biochem Pharmacol 53(8):1197-1202