Naporafenib Combinations Prove Effective in NRAS-Mutant Unresectable/Metastatic Melanoma
Source: Onc Live, September 2022
The investigational type II RAF inhibitor naporafenib exhibited favorable efficacy with a tolerable safety profile in combination with rineterkib, trametinib (Mekinist), or ribociclib (Kisqali) in patients with previously treated, unresectable or metastatic melanoma, according to results from a phase 2 trial (NCT04417621) presented at the ESMO Congress 2022.
In a pooled analysis, the combinations displayed promising efficacy among 85 patients with NRAS-mutant disease with a confirmed partial response (cPR) rate of all the combinations was 21% with 40% of patients achieving stable disease (SD). Additionally, the disease control rate (DCR) was 61% (95% CI, 49%-71%). Disease progression (PD) was reported in 28% of patients in this cohort. The disease control rate (DCR) was 61% (95% CI, 49%-71%).
“Naporafenib is an orally bioavailable small molecule,” Céleste Lebbé, MD, PhD, professor of dermato-oncology and CIC, Universite Paris Cite, AP-HP, Hopital Saint-Louis, in France, said during a presentation of the findings. “It is a type II pan-RAF inhibitor, which is selective for both BRAF wild-type and V600 and CRAF. Thereby it inhibits that kinase signalization without the risk of paradoxical activation in normal cells.”