Filanesib (ARRY-520) in Combination With Pomalidomide and Dexamethasone for Relapsed/Refractory (R/R) Multiple Myeloma (MM) Patients

Summary

Phase I/II, Multicenter, Open Label, Clinical Trial to evaluate safety and efficacy and determine the Maximum Tolerated Dose (MTD) of Filanesib in combination with pomalidomide and dexamethasone in relapsed/refractory (R/R) Multiple Myeloma (MM) patients

Timeline

Start

2015-09

Primary completion

2018-02

Completion

2020-03-23

Publications

• Background Kyle RA, Rajkumar SV. Multiple myeloma. N Engl J Med. 2004 Oct 28;351(18):1860-73. doi: 10.1056/NEJMra041875. No abstract available.
• Background Kyle RA, Rajkumar SV. Multiple myeloma. Blood. 2008 Mar 15;111(6):2962-72. doi: 10.1182/blood-2007-10-078022.
• Background Kumar SK, Lee JH, Lahuerta JJ, Morgan G, Richardson PG, Crowley J, Haessler J, Feather J, Hoering A, Moreau P, LeLeu X, Hulin C, Klein SK, Sonneveld P, Siegel D, Blade J, Goldschmidt H, Jagannath S, Miguel JS, Orlowski R, Palumbo A, Sezer O, Rajkumar SV, Durie BG; International Myeloma Working Group. Risk of progression and survival in multiple myeloma relapsing after therapy with IMiDs and bortezomib: a multicenter international myeloma working group study. Leukemia. 2012 Jan;26(1):149-57. doi: 10.1038/leu.2011.196. Epub 2011 Jul 29.
• Background Ocio EM, Richardson PG, Rajkumar SV, Palumbo A, Mateos MV, Orlowski R, Kumar S, Usmani S, Roodman D, Niesvizky R, Einsele H, Anderson KC, Dimopoulos MA, Avet-Loiseau H, Mellqvist UH, Turesson I, Merlini G, Schots R, McCarthy P, Bergsagel L, Chim CS, Lahuerta JJ, Shah J, Reiman A, Mikhael J, Zweegman S, Lonial S, Comenzo R, Chng WJ, Moreau P, Sonneveld P, Ludwig H, Durie BG, Miguel JF. New drugs and novel mechanisms of action in multiple myeloma in 2013: a report from the International Myeloma Working Group (IMWG). Leukemia. 2014 Mar;28(3):525-42. doi: 10.1038/leu.2013.350. Epub 2013 Nov 20.
• Background Mateos MV, Ocio EM, San Miguel JF. Novel generation of agents with proven clinical activity in multiple myeloma. Semin Oncol. 2013 Oct;40(5):618-33. doi: 10.1053/j.seminoncol.2013.07.005.
• Background Miguel JS, Weisel K, Moreau P, Lacy M, Song K, Delforge M, Karlin L, Goldschmidt H, Banos A, Oriol A, Alegre A, Chen C, Cavo M, Garderet L, Ivanova V, Martinez-Lopez J, Belch A, Palumbo A, Schey S, Sonneveld P, Yu X, Sternas L, Jacques C, Zaki M, Dimopoulos M. Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): a randomised, open-label, phase 3 trial. Lancet Oncol. 2013 Oct;14(11):1055-1066. doi: 10.1016/S1470-2045(13)70380-2. Epub 2013 Sep 3.
• Background Ocio EM, Mitsiades CS, Orlowski RZ, Anderson KC. Future agents and treatment directions in multiple myeloma. Expert Rev Hematol. 2014 Feb;7(1):127-41. doi: 10.1586/17474086.2014.858595. Epub 2013 Dec 18.
• Background Blangy A, Lane HA, d'Herin P, Harper M, Kress M, Nigg EA. Phosphorylation by p34cdc2 regulates spindle association of human Eg5, a kinesin-related motor essential for bipolar spindle formation in vivo. Cell. 1995 Dec 29;83(7):1159-69. doi: 10.1016/0092-8674(95)90142-6.
• Background Stern BM, Murray AW. Lack of tension at kinetochores activates the spindle checkpoint in budding yeast. Curr Biol. 2001 Sep 18;11(18):1462-7. doi: 10.1016/s0960-9822(01)00451-1.
• Background Tunquist BJ, Woessner RD, Walker DH. Mcl-1 stability determines mitotic cell fate of human multiple myeloma tumor cells treated with the kinesin spindle protein inhibitor ARRY-520. Mol Cancer Ther. 2010 Jul;9(7):2046-56. doi: 10.1158/1535-7163.MCT-10-0033. Epub 2010 Jun 22.
• Background Boiani M, Daniel C, Liu X, Hogarty MD, Marnett LJ. The stress protein BAG3 stabilizes Mcl-1 protein and promotes survival of cancer cells and resistance to antagonist ABT-737. J Biol Chem. 2013 Mar 8;288(10):6980-90. doi: 10.1074/jbc.M112.414177. Epub 2013 Jan 22.
• Background Lonial S, Shah JJ, Zonder J, Bensinger WI, Cohen AD, Kaufman JL, et al. Prolonged Survival and Improved Response Rates With ARRY-520 In Relapsed/Refractory Multiple Myeloma (RRMM) Patients With Low α-1 Acid Glycoprotein (AAG) Levels: Results From a Phase 2 Study. Blood. 2013;122(21):285-
• Background Shah JJ, Thomas S, Weber DM, Wang M, Orlowski R. Phase 1 Study Of The Novel Kinesin Spindle Protein Inhibitor Arry-520 + Carfilzomib(Car) In Patients With Relapsed And/Or Refractory Multiple Myeloma (RRMM). Haematologica. 2013;98(S1):Abstract-S579
• Background Humphries MJ, Anderson D, Williams L, Rieger R, Tunquist B, Walker D. ARRY-520 Combined With Pomalidomide Displays Enhanced Anti-Tumor Activity In Preclinical Models Of Multiple Myeloma. Blood. 2013;122(21):3167
• Results Petrelli NJ, Winer EP, Brahmer J, Dubey S, Smith S, Thomas C, Vahdat LT, Obel J, Vogelzang N, Markman M, Sweetenham JW, Pfister D, Kris MG, Schuchter LM, Sawaya R, Raghavan D, Ganz PA, Kramer B. Clinical Cancer Advances 2009: major research advances in cancer treatment, prevention, and screening--a report from the American Society of Clinical Oncology. J Clin Oncol. 2009 Dec 10;27(35):6052-69. doi: 10.1200/JCO.2009.26.6171. Epub 2009 Nov 9. No abstract available.
• Results Kumar SK, Rajkumar SV, Dispenzieri A, Lacy MQ, Hayman SR, Buadi FK, Zeldenrust SR, Dingli D, Russell SJ, Lust JA, Greipp PR, Kyle RA, Gertz MA. Improved survival in multiple myeloma and the impact of novel therapies. Blood. 2008 Mar 1;111(5):2516-20. doi: 10.1182/blood-2007-10-116129. Epub 2007 Nov 1.
• Results Richardson PG, Sonneveld P, Schuster MW, Irwin D, Stadtmauer EA, Facon T, Harousseau JL, Ben-Yehuda D, Lonial S, Goldschmidt H, Reece D, San-Miguel JF, Blade J, Boccadoro M, Cavenagh J, Dalton WS, Boral AL, Esseltine DL, Porter JB, Schenkein D, Anderson KC; Assessment of Proteasome Inhibition for Extending Remissions (APEX) Investigators. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med. 2005 Jun 16;352(24):2487-98. doi: 10.1056/NEJMoa043445.
• Results Singhal S, Mehta J, Desikan R, Ayers D, Roberson P, Eddlemon P, Munshi N, Anaissie E, Wilson C, Dhodapkar M, Zeddis J, Barlogie B. Antitumor activity of thalidomide in refractory multiple myeloma. N Engl J Med. 1999 Nov 18;341(21):1565-71. doi: 10.1056/NEJM199911183412102.
• Results Dimopoulos M, Spencer A, Attal M, Prince HM, Harousseau JL, Dmoszynska A, San Miguel J, Hellmann A, Facon T, Foa R, Corso A, Masliak Z, Olesnyckyj M, Yu Z, Patin J, Zeldis JB, Knight RD; Multiple Myeloma (010) Study Investigators. Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N Engl J Med. 2007 Nov 22;357(21):2123-32. doi: 10.1056/NEJMoa070594.
• Results Weber DM, Chen C, Niesvizky R, Wang M, Belch A, Stadtmauer EA, Siegel D, Borrello I, Rajkumar SV, Chanan-Khan AA, Lonial S, Yu Z, Patin J, Olesnyckyj M, Zeldis JB, Knight RD; Multiple Myeloma (009) Study Investigators. Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America. N Engl J Med. 2007 Nov 22;357(21):2133-42. doi: 10.1056/NEJMoa070596.
• Results Milross CG, Mason KA, Hunter NR, Chung WK, Peters LJ, Milas L. Relationship of mitotic arrest and apoptosis to antitumor effect of paclitaxel. J Natl Cancer Inst. 1996 Sep 18;88(18):1308-14. doi: 10.1093/jnci/88.18.1308.
• Results Oltersdorf T, Elmore SW, Shoemaker AR, Armstrong RC, Augeri DJ, Belli BA, Bruncko M, Deckwerth TL, Dinges J, Hajduk PJ, Joseph MK, Kitada S, Korsmeyer SJ, Kunzer AR, Letai A, Li C, Mitten MJ, Nettesheim DG, Ng S, Nimmer PM, O'Connor JM, Oleksijew A, Petros AM, Reed JC, Shen W, Tahir SK, Thompson CB, Tomaselli KJ, Wang B, Wendt MD, Zhang H, Fesik SW, Rosenberg SH. An inhibitor of Bcl-2 family proteins induces regression of solid tumours. Nature. 2005 Jun 2;435(7042):677-81. doi: 10.1038/nature03579. Epub 2005 May 15.
• Ocio EM, Motllo C, Rodriguez-Otero P, Martinez-Lopez J, Cejalvo MJ, Martin-Sanchez J, Blade J, Garcia-Malo MD, Dourdil MV, Garcia-Mateo A, de Arriba F, Garcia-Sanz R, de la Rubia J, Oriol A, Lahuerta JJ, San-Miguel JF, Mateos MV. Filanesib in combination with pomalidomide and dexamethasone in refractory MM patients: safety and efficacy, and association with alpha 1-acid glycoprotein (AAG) levels. Phase Ib/II Pomdefil clinical trial conducted by the Spanish MM group. Br J Haematol. 2021 Feb;192(3):522-530. doi: 10.1111/bjh.16788. Epub 2020 Jun 5.

Drugs

Indications