Roche Holding AG — Rozlytrek EMA EPAR variation assessment report (EMEA/H/C/004936, 2020)
Roche Holding AG · 2020 · EMA EPAR variation assessment report · company profile →
Report summary
This EMA report assesses a variation for Rozlytrek (entrectinib) to expand its indication for NTRK gene fusion-positive solid tumors to pediatric patients (1 month to <12 years) and add a new pediatric ROS1 indication. It details the prevalence of these fusions, the development of a new granular formulation, and non-clinical pharmacology. Pharmacokinetic and toxicology studies, including bone metabolism effects and bioequivalence of formulations, are presented. Efficacy data from STARTRK-NG, TAPISTRY, and STARTRK-2 trials show a 72.7% objective response rate for NTRK-positive tumors. Safety data from 91 pediatric patients reveal a high incidence of adverse events (98.9%), with 69.2% being Grade 3-4, and bone fractures in 29.7%. Despite safety concerns, particularly fractures, the CHMP concluded a positive benefit-risk balance for NTRK fusion-positive tumors, recommending marketing authorization extension with conditions for further data collection. The ROS1 indication was not pursued due to limited data.
Key findings — cited to the page
| Patients with Grade 3 AE of weight increased | 18.7 % | · p.111 |
| QT prolongation events (any grade) in expanded paediatric population | 5.5 % | · p.110 |
| Grade 1 QT prolongation events | 3.3 % | · p.110 |
| Patients with Grade 1-2 AEs of weight increased | 19.8 % | · p.111 |
| Grade 3 CHF events | 1.1 % | · p.109 |
| Grade 4 CHF events | 1.1 % | · p.109 |
| Pediatric patients with at least one mild to severe bone fracture (Grade 1 to 3) | 18 (25%) | · p.51 |
| Grade 2 CHF events | 1.1 % | · p.109 |
| Grade 1 CHF events | 2.2 % | · p.109 |
| Grade 2 QT prolongation events | 2.2 % | · p.110 |
| Pediatric patients with treatment-emergent AE grade 3 or higher | 55 (75%) | · p.48 |
| Patients with Grade 2 and Grade 3 weight decrease | 2.2 % | · p.111 |
Source: Roche Holding 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 →