In Brief: Phase III Trials in Multiple Myeloma

• Plitidepsin(Aplidin; PharmaMar, SA), which induces cell death through various cellular pathways, was originally isolated from a marine organism known as a sea squirt.¹A randomized, multicenter, open-label, phase III study of plitidepsin in combination with dexamethasone vs dexamethasone alone in patients with relapsed/refractory multiple myeloma is currently recruiting participants.²

• Elotuzumab(HuLuc63; Bristol-Myers Squibb (BMS), AbbVie) is a humanized monoclonal antibody that binds to the cell surface glycoprotein CA1. The cell surface protein is found primarily on myeloma cells (not on normal bone marrow cells).³A phase III study of lenalidomide and dexamethasone with or without elotuzumab to treat newly diagnosed, previously untreated multiple myeloma (ELOQUENT 1) is currently recruiting participants.⁴
• A phase III study of lenalidomide and dexamethasone with or without elotuzumab to treat relapsed or refractory multiple myeloma (ELOQUENT-2) is ongoing but not recruiting participants^.5

• Carfilzomib(Kyprolis; Onyx Therapeutics) is a selective proteasome inhibitor.⁶A phase III study with carfilzomab and dexamethason versus Velcade and dexamethasone for relapsed multiple myeloma patients (ENDEAVOR) is currently recruiting participants.⁷
• A phase III study of carfilzomib, melphalan, prednisone vs bortezomib, melphalan, prednisone in newly diagnosed multiple myeloma (CLARION) is currently recruiting participants.⁸

• Masitinib(AB1010; AB Science) is a protein kinase inhibitor.⁹A phase III study to evaluate the efficacy and safety of masitinib in patients with relapsed or refractory multiple myeloma is currently recruiting participants.¹⁰

• Panobinostat(LBH589; Novartis) is a highly potent pan-deacetylase inhibitor (pan-DACi), (inclusive of HDAC6) that disrupts aggresome function, promotes accumulation of cytotoxic misfolded protein aggregates, and triggers myeloma cell death.¹¹A multicenter, randomized, double-blind, placebo controlled phase III study of panobinostat in combination with bortezomib and dexamethasone in patients with relapsed multiple myeloma is ongoing (not recruiting).¹²

References

1. Munoz-Alonso, Gonzalex-Santiago L, Martinez T, et al. The mechanism of action of plitidepsin. Curr Opin Drugs. 2009;10:536-542. http://www.ncbi.nlm.nih.gov/pubmed/19513942
2. Clinicaltrials.gov. Aplidin - Dexamethasone in Relapsed/Refractory Myeloma (ADMYRE). Available at: http://clinicaltrials.gov/show/NCT01102426
3. National Cancer Institute (NCI). Elotuzumab. Available at: http://www.cancer.gov/drugdictionary?cdrid=532249
4. Clinicaltrials.gov. Phase III Study of Lenalidomide and Dexamethasone With or Without Elotuzumab to Treat Newly Diagnosed, Previously Untreated Multiple Myeloma (ELOQUENT-1). Available at: http://clinicaltrials.gov/ct2/show/NCT01335399?term=elotuzumab&rank=8 Millennium: The Takeda Oncology Company. Newsroom. Available at: http://investor.millennium.com/phoenix.zhtml?c=80159&p=irol-newsArticle&ID=1826370&highlight=
5. Clinicaltrials.gov. Phase III Study of Lenalidomide and Dexamethasone With or Without Elotuzumab to Treat Relapsed or Refractory Multiple Myeloma (ELOQUENT - 2). Available at: http://clinicaltrials.gov/show/NCT01239797
6. National Cancer Institute (NCI). Carfilzomib. Available at: http://www.cancer.gov/drugdictionary?CdrID=459751
7. Clincaltrials.gov. Phase 3 Study With Carfilzomib and Dexamethasone Versus Velcade and Dexamethasone for Relapsed Multiple Myeloma Patients (ENDEAVOR). Available at: http://clinicaltrials.gov/ct2/show/NCT01568866?term=carfilzomib+and+multiple+myeloma&rank=5
8. Clinicaltrials.gov. Phase 3 Study of Carfilzomib, Melphalan, Prednisone vs Bortezomib, Melphalan, Prednisone in Newly Diagnosed Multiple Myeloma (CLARION). Available at: http://clinicaltrials.gov/ct2/show/NCT01818752?term=CLARION&rank=1
9. National Cancer Institute (NCI). Masitinib mesylate. Available at: http://www.cancer.gov/drugdictionary?CdrID=629109
10. Clinicaltrials.gov. A Phase 3 Study to Evaluate Efficacy and Safety of Masitinib in Patients With Relapse or Refractory Multiple Myeloma. Available at: http://clinicaltrials.gov/ct2/show/NCT01470131?term=masitinib+and+multiple+myeloma&rank=1
11. National Cancer Institute (NCI). Panobinostat. Available at: http://www.cancer.gov/drugdictionary?cdrid=530790
12. Clinicaltrials.gov. Panobinostat or Placebo With Bortezomib and Dexamethasone in Patients With Relapsed Multiple Myeloma (PANORAMA-1). Available at: http://clinicaltrials.gov/ct2/show/NCT01023308?term=PANORAMA+I+and+multiple+myeloma&rank