Tafinlar + Mekinist demonstrates unprecedented efficacy in pediatric patients with BRAF V600 low-grade gliomas in phase II/III study.

In this study, patients randomized to receive Tafinlar + Mekinist experienced a statistically significant overall response rate (ORR) of 47% (CI: 35-59%) compared to 11% (CI: 3-25%, p<0.001) for those randomized to receive chemotherapy. a new liquid formulation of tafinlar + mekinist that can be easier to administer than chemotherapy was used in this trial. the data will be highlighted today as part of an official press briefing and oral presentation at the 2022 american society of clinical oncology (asco) annual meeting (abstract #lba2002).

Pediatric low-grade glioma is the most common pediatric brain cancer and BRAF V600 mutations are present in 15-20% of pLGGs. Currently, standard chemotherapy is associated with poor outcomes and a high burden of care.

Additional results from the Phase II/III trial showed at a median follow-up of 18.9 months, median progression-free survival (PFS) was 20.1 months with Tafinlar + Mekinist (CI: 12.8 months-not estimable) compared to 7.4 months with chemotherapy (CI: 3.6-11.8 months, hazard ratio=0.31 [CI: 0.17-0.55] [p<0.001]). additionally, tumors shrank or remained stable in 86% of patients in the tafinlar + mekinist arm (n="73;" ci: 76-93%) compared to 46% of patients in the chemotherapy arm (n="37;" ci: 30-63%). after one year of follow-up, nearly all patients on tafinlar + mekinist (89%) had a reduction in tumor size compared with baseline versus 70% of patients in the chemotherapy arm. results from a quality-of-life analysis favored tafinlar + mekinist compared to chemotherapy at all time points.

The safety profile of Tafinlar + Mekinist was generally consistent with established safety observed in previous studies. Patients in the Tafinlar + Mekinist arm had fewer grade 3 or higher adverse events (AEs; 47% vs 94%) and fewer discontinuations due to AEs (4% vs 18%) than patients in the chemotherapy arm evaluated for safety (n=33). The most frequent AEs in the Tafinlar + Mekinist arm were pyrexia, headache and vomiting.

In a separate single-arm cohort of this study evaluating pediatric patients with relapsed or refractory BRAF V600 high-grade gliomas (HGG), treatment with Tafinlar + Mekinist showed an independently assessed ORR of 56.1% [CI: 39.7%-71.5%] and generally consistent safety results . These data were presented in a poster discussion at the 2022 ASCO Annual Meeting (Abstract #2009).

About the TADPOLE trial : This global Phase II/III, multicenter, open-label trial is evaluating patients aged 1 to 17 with BRAF V600 LGG (n=110) or relapsed or refractory HGG (n=41). Tafinlar + Mekinist is administered orally either as new liquid formulations, or as capsules and tablets, respectively. The primary endpoint in both cohorts is overall response rate. Secondary outcome measures include duration of response, progression-free survival, overall survival and other endpoints.