Antitumor Activity of KIN-2787, a Next-Generation pan-RAF Inhibitor, in Preclinical Models of Human BRAF-alteration Driven Non-small Cell Lung Cancer (NSCLC) (IASLC-TTLC 2022)
While the RAF inhibitor dabrafenib is approved for treatment of BRAF Class I-altered NSCLC (in combination with trametinib), there are no RAF targeted therapies for treatment of NSCLC patients with tumors driven by BRAF Class II or Class III dimer-dependent alterations, likely contributing to the inferior clinical outcomes of these patients (Dagogo-Jack et al...In contrast to dabrafenib or vemurafenib, approved BRAF inhibitors with activity limited to Class I BRAF alterations, KIN-2787 was most active in Class II and Class III BRAF mutant NSCLC cells (EC50 median values 264 nM and 24 nM, respectively)...A Phase I dose-escalation and expansion clinical trial evaluating the safety and efficacy of KIN-2787 is actively enrolling (NCT04913285). Patients with advanced and metastatic solid tumors, including NSCLC patients, whose cancers are driven by BRAF Class I, II, or III alterations will receive KIN-2787 treatment on this study.