Efficacy and safety of ripretinib in patients with KIT-altered metastatic melanoma.
Date
2022-08-01ICR Author
Author
Janku, F
Bauer, S
Shoumariyeh, K
Jones, RL
Spreafico, A
Jennings, J
Psoinos, C
Meade, J
Ruiz-Soto, R
Chi, P
Type
Journal Article
Metadata
Show full item recordAbstract
BACKGROUND: Ripretinib, a broad-spectrum KIT and platelet-derived growth factor receptor A switch-control tyrosine kinase inhibitor, is approved for the treatment of adult patients with advanced gastrointestinal stromal tumor as ≥ fourth-line therapy. We present the efficacy and safety of ripretinib in patients with KIT-altered metastatic melanoma enrolled in the expansion phase of the ripretinib phase I study. PATIENTS AND METHODS: Patients with KIT-altered metastatic melanoma were enrolled and treated with ripretinib at the recommended phase II dose of 150 mg once daily in 28-day cycles. Investigator-assessed responses according to Response Evaluation Criteria In Solid Tumors version 1.1 were carried out on day 1 of cycles 3, 5, 7, every three cycles thereafter, and at a final study visit. RESULTS: A total of 26 patients with KIT-altered metastatic melanoma (25 with KIT mutations, 1 with KIT-amplification) were enrolled. Patients had received prior immunotherapy (n = 23, 88%) and KIT inhibitor therapy (n = 9, 35%). Confirmed objective response rate (ORR) was 23% [95% confidence interval (CI) 9%-44%; one complete and five partial responses] with a median duration of response of 9.1 months (range, 6.9-31.3 months). Median progression-free survival (mPFS) was 7.3 months (95% CI 1.9-13.6 months). Patients without prior KIT inhibitor therapy had a higher ORR and longer mPFS (n = 17, ORR 29%, mPFS 10.2 months) than those who had received prior KIT inhibitor treatment (n = 9, ORR 11%, mPFS 2.9 months). The most common treatment-related treatment-emergent adverse events (TEAEs) of any grade in ≥15% of patients were increased lipase, alopecia, actinic keratosis, myalgia, arthralgia, decreased appetite, fatigue, hyperkeratosis, nausea, and palmar-plantar erythrodysesthesia syndrome. There were no grade ≥4 treatment-related TEAEs. CONCLUSIONS: In this phase I study, ripretinib demonstrated encouraging efficacy and a well-tolerated safety profile in patients with KIT-altered metastatic melanoma, suggesting ripretinib may have a clinically meaningful role in treating these patients.
Collections
Subject
KIT
melanoma
ripretinib
tyrosine kinase inhibitor
Adult
Gastrointestinal Stromal Tumors
Humans
Melanoma
Naphthyridines
Protein Kinase Inhibitors
Urea
Language
eng
Date accepted
2022-05-25
License start date
2022-08-01
Citation
ESMO Open, 2022, 7 (4), pp. 100520 -
Publisher
ELSEVIER