Novartis Announces Results From Phase II Study On Tafinlar + Mekinist

(RTTNews) - Novartis (NVS) announced results from a Phase II study showing a durable survival benefit for some patients with BRAF V600 mutation-positive metastatic melanoma or MM when treated with the combination of Tafinlar or dabrafenib + Mekinist (trametinib).

The findings from the landmark five-year analysis of the trial, BRF113220, represent the longest follow-up to date of a BRAF and MEK inhibitor combination therapy in this patient population, and were presented today at the 53rd Annual Meeting of the American Society of Clinical Oncology in Chicago.

A total of 162 patients received either Tafinlar monotherapy (150 mg BID) (n = 54) or the Tafinlar + Mekinist combination (150 mg BID/2 mg QD) (n = 54). After five years, 20 patients (37%) remain in the study, including seven (13%) in the Tafinlar monotherapy arm and 13 (24%) in the combination therapy arm, demonstrating that overall survival (OS) with combination therapy is superior to monotherapy[1]. The four-and five-year OS rates with monotherapy were 23% and 21%, respectively. The four- and five-year OS rates with combination therapy were 30% and 28%, respectively, reflecting a stabilization of OS in patients enrolled in the study[1].

Progression-free survival or PFS in the monotherapy arm was consistently 3% whereas PFS at both four and five years was 13%, also demonstrating stabilization[1]. Forty-five of 54 patients (83%) in the Tafinlar monotherapy arm included in this updated analysis had crossed over to Tafinlar + Mekinist combination (150 mg BID/2 mg QD); the survival outcomes in these crossover patients continued to be followed under the Tafinlar arm.

Adverse events were consistent with other Tafinlar + Mekinist studies, and additional follow-up revealed no new safety signals.

Additionally, Novartis presented results from a Phase II study showing a positive, statistically significant intracranial response for patients with BRAF V600 mutation-positive metastatic melanoma (MM) when treated with the combination of Tafinlar + Mekinist. The findings from the 30-month trial, COMBI-MB, represent the first report of a Phase II trial evaluating a BRAF and MEK inhibitor combination therapy in patients with BRAF V600-mutant melanoma brain metastases (MBM).

The COMBI-MB study evaluated Tafinlar + Mekinist in 125 patients enrolled in four cohorts. In Cohort A (patients who were BRAF V600E mutation-positive, had asymptomatic MBM and no local prior treatment), investigator-assessed intracranial response rate (IRR) was 58% (95% CI: 46, 69). Extracranial response rate (ERR) was 55% (95% CI: 43, 67) and overall response rate (ORR) was 58% (95% CI: 46, 69). Median PFS was 5.6 months (95% CI: 5.3, 7.4). Six-month OS was 79%; with 31 patients (41%) still in follow-up. Preliminary median OS was 10.8 months (95% CI: 8.7, 19.6).

Adverse events across cohorts (any, 98%; grade 3/4, 48%) were consistent with prior Tafinlar + Mekinist studies; 10% of patients (8% in cohort A) discontinued due to adverse events.