Table II.
Additional targeted therapies in early development for multiple myeloma.
| Target | Agents in development | Stage of development for multiple myeloma |
|---|---|---|
| Proteasome | Salinosporamide (NPI-0052) | Phase 1 |
| ONX 0912 (formerly PR-047) | Preclinical (phase 1 to begin in 2010) | |
| S-2209 | Preclinical | |
| HSP90 | Retaspimycin (IPI-504) | Phase 1 |
| Alvespimycin (KOS-1022, 17-DMAG) | Phase 1 | |
| VER-52296/NVP-AUY922 | Phase 1 | |
| SNX-5422 | Phase 1 | |
| STA-9090 | Phase 1/2 in haematological malignancies | |
| AT13387 | Phase 1 | |
| VEGF | VEGF receptor inhibitor: bevacizumab | Phase 2 |
| VEGF receptor inhibitor: pazopanib | Phase 2 | |
| TNF-related apoptosis-inducing ligand (TRAIL) and FAS (CD95) | Antibodies (eg, mapatumumab) and other agents (eg, Mega-FAS) that activate these receptors | Phase 2 |
| IL-6 and TNF | Atiprimod | Phase 1 |
| c-KIT/PDGFR | Dasatinib | Phase 2 |
| FGF-3 receptor [in patients carrying the t(4;14) translocation] | Dovitinib | Phase 1 |
| Masitinib (AB1010) | Phase 2 | |
| IGF-1 | Antibody that blocks IGF-1 ligand-receptor binding: | Phase 1 |
| AVE-1642 | ||
| HDAC | Panobinostat (LBH589) | Phase 2 |
| Depsipeptide | Phase 1/2 | |
| ITF2357 | Phase 2 | |
| CS1 | Elotuzumab (HuLuc63) | Phase 1/2 |
| CD40 | SGN-40 | Phase 1 |
| HCD122 (formerly CHIR-12·12) | Phase 1 | |
| CD74 | Milatuzumab (humanized anti-CD74 monoclonal antibody) | Phase 1/2 |
| Farnesyl transferase | Tipifarnib | Phase 2 |
| Heparanase | SST0001 | Preclinical |
| MAPK | AZD6244 | Phase 2 |
| CDKs | PD 0332991 – inhibits CDK4/6 | Phase 1/2 |
| AT7519 – multi-CDK inhibitor | Phase 1 (phase 2 to begin in 2010) | |
| Bcl-2 | AT-101 | Phase 1/2 |
| ABT-263 | Phase 1 | |
| GX15-070 | Phase 1/2 | |
| Survivin | Antisense oligonucleotide LY2181308; ribozymes targeting BIRC5 mRNA; small interfering RNAs that suppress survivin; small molecule antagonists that inhibit survivin phosphorylation, expression, or binding to HSP90 | Phase 1 |
| Aurora A kinase | ENMD-981693 | Preclinical |
| MLN8237 | Phase 1/2 | |
| Various myeloma-specific tumour antigens | Vaccines that stimulate T-cell response to these antigens: WTI peptide, idiotype, survivin; dendritic cells loaded with whole myeloma cells; dendritic cells loaded with idiotype, survivin, or other tumour antigens; intratumoural injections of naive dendritic cells | Phase 2 |
| Multiple targets | Arsenic trioxide | Phase 2/3 |
CDKs, cyclin-dependent kinases; HSP90, heat shock protein 90; IGF-1, insulin-like growth factor-1; IL-6, interleukin-6; MAPK, mitogen-activated protein kinase; PDGFR, platelet-derived growth factor receptor; TNF, tumour necrosis factor; VEGF, vascular endothelial growth factor.