Novartis AG — Mekinist EMA EPAR variation assessment report (EMEA/H/C/002643, 2014)

Novartis AG · 2014 · EMA EPAR variation assessment report · company profile →

Report summary

Novartis Europharm Limited submitted a Type II variation to the EMA for Tafinlar (dabrafenib) and Mekinist (trametinib) to extend their indication to BRAF V600E mutation-positive differentiated thyroid cancer (DTC). This application is based on the pivotal Phase 3 study CDRB436J12301, which evaluated dabrafenib plus trametinib (D+T) against placebo in previously treated, locally advanced or metastatic, radioactive iodine refractory DTC. The study, involving 153 patients randomized 2:1, demonstrated statistically significant improvements in progression-free survival (PFS) and objective response rate (ORR) for D+T. Although overall survival (OS) did not reach statistical significance in the primary analysis, a sensitivity analysis suggested a stronger benefit. While D+T showed higher rates of adverse events, these were manageable. The positive benefit-risk balance supports the extended indication.

Key findings — cited to the page

general disorders and administration site conditions (all grades) in D+T arm	67.3 %	J12301 · p.69
infections and infestations (all grades) in D+T arm	66.3 %	J12301 · p.70
blood and lymphatic system disorders (all grades) in D+T arm	55.4 %	J12301 · p.69
blood and lymphatic system disorders (Grade ≥3) in placebo arm	0 %	J12301 · p.69
general disorders and administration site conditions (Grade ≥3) in D+T arm	6.9 %	J12301 · p.69
general disorders and administration site conditions (Grade ≥3) in placebo arm	1.9 %	J12301 · p.69
patients in D+T arm with grade ≥ 3 AEs	54.5 %	J12301 · p.69
patients in placebo arm with grade ≥ 3 AEs	26.9 %	J12301 · p.69
blood and lymphatic system disorders (all grades) in placebo arm	11.5 %	J12301 · p.69
blood and lymphatic system disorders (Grade ≥3) in D+T arm	7.9 %	J12301 · p.69
general disorders and administration site conditions (all grades) in placebo arm	34.6 %	J12301 · p.69
infections and infestations (all grades) in placebo arm	36.5 %	J12301 · p.70

Source: Novartis AG ↗ · License: EMA - reuse permitted with acknowledgement. Summary and findings are extracted from the published document; every figure cites its page. Informational only — not investment advice. Explore the Oncology library →