Table 3.
Clinical melanoma subtype, associated KIT alterations, clinical response to prior therapy with a KIT inhibitor and clinical response to nilotinib in those with CNS involvement.
| 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 in non- CNS Lesions (Best Percent Respons e) |
RECIST Respons e to Nilotinib in CNS Lesions (Best Percent Respons e) |
PFS to Nilotini b (Month s) |
|---|---|---|---|---|---|---|---|---|---|
| 4 | Mucosal | Exon 11 V560D |
Not Present (FISH) |
None | n/a | n/a | SD (−20%) |
PR (−36%)* |
3.9 |
| 6 | Acral | Exon 11 W577R |
Not Present (FISH) |
Imatinib | Unk | Unk | SD (−23%) |
SDa (11%) |
6.6 |
| 7 | Acral | None | Present (qPCR) |
Imatinib | PD | 1.7 | SD (3%) |
PD (37.5%) |
2.1 |
| 10 | Cutaneo us |
Exon 11 V560D |
Not tested | Imatinib | PR | 4.6 | PD (44%) |
PD (40%) |
2.4 |
| 15 | Mucosal | Exon 11 L576P |
Not tested | None | n/a | n/a | n/ab | SD (−25%) |
2.9 |
| 16 | Mucosal | Exon 13 Y646D |
Not tested | Imatinib | SD | ~ 4 | Uneval | Uneval | 0.2 |
| 17 | Mucosal | Exon 18 L831P |
Not Present (FISH) |
Imatinib | SD | ~ 7 | n/ab | SD (9%) |
1.6 |
| 18 | Mucosal | Exon 11 L576P |
Not tested | Imatinib | SD | 2.8 | SD (14%) |
PD (0%)* |
1.8 |
Abbreviations: Unk – Unknown
- 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
- Signifies the development of progression in non-target lesions or the development of new lesions
– Patient 6 underwent resection of one symptomatic brain target lesion 1.6 months after initiation of therapy; a second CNS target lesion remained stable for 6.6 months after initiation of therapy; however, new CNS lesions were noted at that time and the patient was taken off for POD
- No non-CNS lesions present.