Table 2.
Clinical melanoma subtype, associated KIT alterations, clinical response to prior therapy with a KIT inhibitor and clinical response to nilotinib in those without CNS involvement (Cohort A).
| Study Subject # |
Melano ma Subtype |
KIT Mutatio n |
KIT Amplificati on |
Prior KIT Inhibito r+ |
RECIS T Respons e to Prior KIT Inhibito r |
PFS to Prior KIT Inhibito r (Month s) |
RECIST Respons e to Nilotinib (Best Percent Respons e) |
PFS to Nilotini b (Month s) |
|---|---|---|---|---|---|---|---|---|
| 1 | Mucosal | Exon 17 D820Y |
Present (qPCR) |
Imatinib | PR | 3.8 | SD (−26%) |
3.6 |
| 2x | Acral | Exon 13 K642E |
Present (FISH) |
Imatinib | uPR | 4.1 | PD (6%)* |
0.8 |
| 3 | Mucosal | Exon 11 L576P |
Not Present (FISH) |
Imatinib | PR | 12.4 | PR (−59%) |
37.5+ |
| 5 | Mucosal | None | Present (qPCR) |
Imatinib | SD | 11.5 | Clinical PD |
0.9 |
| 8 | CSD | Exon 17 N822K |
Present (FISH) |
Imatinib | SD | 8.3 | SD (0%) |
3.3 |
| 9 | Mucosal | Exon 13 R643Q and K642E |
Not tested | Imatinib | Unk | Unk | SD (14%) |
3.9 |
| 11 | CSD | Exon 11 V559C |
Present (FISH) |
Imatinib | SD | 16 | Ineval | 0.1 |
| 12 | Mucosal | Exon 11 L576P |
Present (qPCR) |
Imatinib | PR | 7 | Clinical PD |
1.8 |
| 13 | Acral | Exon 11 WKVV E 557–561 |
Not tested | Imatinib | SD | 8 | PD* (18%) |
2.1 |
| 14 | Mucosal | Exon 13 K642E |
Not tested | Imatinib | SD | 3 | SD (−22%) |
5.5 |
| 20 | Mucosal | Exon 13 K642E |
Present (qPCR) |
Imatinib | CR | 20 | PR (−54%) |
11.5 |
Abbreviations: qPCR – quantitative polymerase chain reaction
+
- All patients previously treated with a KIT inhibitor experienced progression on those agents and were not enrolled onto this study due to intolerance of prior therapy
x
– Patient 2 also received sorafenib; however, his response to this therapy is not known.
*
- Signifies the development of progression in non-target lesions or the development of new lesions