Table 1.
List of currently investigated targeted therapies in advanced melanoma (information obtained from www.clinicaltrials.gov)
| Target | Molecular eligibility | Drug | Phase | NCT ID | Conditions |
|---|---|---|---|---|---|
| RTK | ERBB4 mutation positive | Lapatinib | Phase II | NCT01264081 | Unresectable metastatic melanoma |
| RTK | KIT alteration present | Nilotinib | Phase II | NCT01099514 | Unresectable metastatic melanoma with KIT aberration |
| RTK | KIT alteration present | Sunitinib | Phase II | NCT00631618 | Unresectable metastatic melanoma |
| RTK | KIT alteration present | Nilotinib | Phase II | NCT00788775 | Unresectable metastatic melanoma, which failed other TKIs |
| RTK | KIT alteration present | Nilotinib | Phase II | NCT01168050 | Unresectable metastatic melanoma |
| RTK | KIT alteration present | Sunitinib | Phase II | NCT00577382 | Unresectable metastatic mucosal, acral/lentiginous melanoma |
| RTK | KIT mutation of exon 9, 11, 13, or exon 17 (Y822D and mutations D820Y, Y823D) | Nilotinib vs. dacarbazine | Phase III | NCT01028222 | Unresectable metastatic melanoma |
| RTK (c-Kit selective) | KIT juxtamembrane mutation | Masitinib vs. dacarbazine | Phase III | NCT01280565 | Unresectable metastatic melanoma |
| TK | KIT alteration present | Imatinib mesylate | Phase II | NCT00470470 | Unresectable metastatic melanoma |
| TK | BRAF mutation positive | Lenvatinib (E7080) | Phase II | NCT01136967 | Unresectable metastatic melanoma |
| TK | KIT mutations of exon 11 or 13 | Dasatinib | Phase II | NCT01092728 | Unresectable metastatic melanoma |
| BRAF | BRAF V600E- or V600K-mutation positive | GSK2118436 | Phase II | NCT01266967 | Unresectable metastatic melanoma to the brain |
| BRAF+MEK | BRAF mutation positive | GSK2118436+GSK1120212 | Phase I | NCT01072175 | Unresectable metastatic melanoma |
| BRAF | BRAF V600E mutation positive | GSK2118436 vs. dacarbazine | Phase III | NCT01227889 | BRAF mutant unresectable metastatic melanoma |
| BRAF | BRAF V600 mutation positive | RO5212054 (PLX3603) | Phase I | NCT01143753 | Colorectal cancer, malignant melanoma |
| BRAF | BRAF V600 mutation positive | Vemurafenib | Phase II | NCT01378975 | Unresectable metastatic melanoma (brain metastases) |
| BRAF | BRAF V600E mutation positive | Vemurafenib | Phase III | NCT01307397 | Unresectable metastatic melanoma |
| BRAF+MEK | BRAF V600 mutation positive | Vemurafenib+GDC-0973 | Phase I | NCT01271803 | Unresectable metastatic melanoma |
| MEK | BRAF WT | Docetaxel+selumetinib (AZD6244); docetaxel+placebo | Phase II | NCT01256359 | Unresectable metastatic melanoma |
| MEK | BRAF V600E- or V600K-mutation positive | GSK1120212 vs. dacarbazine or paclitaxel | Phase III | NCT01245062 | BRAF mutant unresectable metastatic melanoma |
| MEK | BRAF V600E or NRAS mutation positive | MEK162 | Phase II | NCT01320085 | BRAF or NRAS mutant unresectable metastatic melanoma |
| MEK | BRAF V600E- or V600K-mutation or a NRAS mutation (codons 12, 13, or 61) positive | Selumetinib (AZD6244) | Phase II | NCT00866177 | Unresectable metastatic melanoma |
| MEK | No GNAQ/GNA11 restrictions | Selumetinib (AZD6244) vs. temozolomide | Phase II | NCT01143402 | Unresectable metastatic uveal melanoma |
| MEK | BRAF V600E mutation positive | TAK-733 | Phase I | NCT00948467 | Unresectable metastatic melanoma |
| CDK | CDK4 mutation or amplification | PD 0332991 | Phase II | NCT01037790 | Advanced cancers |
| mTOR | BRAF V600E mutation positive | Temsirolimus+selumetinib (AZD6244) | Phase II | NCT01166126 | Unresectable metastatic melanoma |
| RTK (c-MET) | No restrictions | ARQ197+sorafenib | Phase I | NCT00827177 | Advanced cancers |
| RTK (VEGFR and c-MET) | No restrictions | Cabozantinib | Phase II | NCT00940225 | Advanced cancers |
| RTK | No restrictions | Pazopanib+paclitaxel | Phase II | NCT01107665 | Unresectable metastatic melanoma |
| RTK | No restrictions | Sunitinib | Phase II | NCT01216657 | Chemorefractory melanoma |
| RTK | No restrictions | Sunitinib+cisplatin+tamoxifen | Phase II | NCT00489944 | High-risk ocular melanoma |
| RTK | No restrictions | Sunitinib+dacarbazine | Phase I/II | NCT00859326 | Unresectable metastatic melanoma |
| RTK | No restrictions | Sunitinib+hydroxychloroquine | Phase I | NCT00813423 | Chemorefractory melanoma |
| TK | No restrictions | Lenvatinib (E7080)+dacarbazine | Phase I/II | NCT01133977 | Unresectable metastatic melanoma |
| RAF | No restrictions | RAF265 | Phase I | NCT00304525 | Unresectable metastatic melanoma |
| RAF | No restrictions | XL281±famotidine | Phase I | NCT00451880 | Advanced cancers |
| RAF (and other kinases) | No restrictions | Sorafenib+cisplatin+tamoxifen | Phase II | NCT00492505 | High-risk stage III melanoma |
| RAF (and other kinases) | No restrictions | Sorafenib vs. placebo | Phase II | NCT01377025 | Unresectable metastatic uveal melanoma |
| MEK | No restrictions | RO4987655 | Phase I | NCT00817518 | Advanced cancers |
| CDK | No restrictions | Dinaciclib | Phase I/II | NCT01026324 | Unresectable metastatic melanoma |
| PI3K+MEK | No restrictions | BKM120+MEK162 | Phase I/II | NCT01363232 | Unresectable metastatic melanoma |
| PI3K/mTOR+MEK | No restrictions | BEZ235+MEK162 | Phase I/II | NCT01337765 | Unresectable metastatic melanoma |
Abbreviations: CDK, cyclin-dependent kinase; mTOR, mammalian target of rapamycin; PI3K, phosphatidylinositol 3-kinase; RTK, receptor tyrosine kinase; TKI, tyrosine kinase inhibitor; VEGFR, vascular endothelial growth factor receptor; WT, wild type.