FDA expands pediatric indication for entrectinib and approves new pellet formulation
Regulatory approval: On Oct 20, 2023, the FDA granted accelerated approval to entrectinib (Rozlytrek) for pediatric patients >1 month old with NTRK gene fusion–positive solid tumors (no known acquired resistance mutation) that are metastatic or where resection would likely cause severe morbidity, and that have progressed after treatment or lack satisfactory standard therapy. The FDA also approved a new oral pellet formulation and added instructions for preparing an oral suspension from capsules.
FDA expands pediatric indication for entrectinib and approves new pellet formulation (Oct 20, 2023)
Type: Regulatory approval (FDA; accelerated approval)
On October 20, 2023, the FDA granted accelerated approval to entrectinib (Rozlytrek; Genentech Inc.) for pediatric patients older than 1 month with solid tumors harboring an NTRK gene fusion (without a known acquired resistance mutation) that are metastatic or where surgical resection is likely to result in severe morbidity, and that have progressed following treatment or have no satisfactory standard therapy. The prior accelerated approval (August 2019) covered pediatric patients ≥12 years for this indication.
The FDA also approved a new oral pellet formulation for entrectinib, and prescribing information now includes instructions for making an oral suspension from capsules.
Supporting evidence
Efficacy was evaluated in 33 pediatric patients treated once daily (20–600 mg based on body surface area, including administration via enteral feeding tube) in two multicenter, single-arm trials: STARTRK-NG (NCT02650401) and TAPISTRY (NCT04589845). The major endpoint was ORR by BICR (RECIST v1.1 for extracranial tumors; RANO for primary CNS tumors). ORR was 70% (95% CI, 51–84) and median DOR was 25.4 months (95% CI, 14.3–not evaluable). Common cancers included primary CNS tumors and infantile fibrosarcoma.
Safety and dosing highlights
In a pooled pediatric safety population (n=76), common (≥20%) adverse reactions included pyrexia, constipation, increased weight, vomiting, diarrhea, nausea, cough, fatigue, pain in extremity, skeletal fracture, decreased appetite, headache, abdominal pain, urinary tract infection, upper respiratory tract infection, and nasal congestion.
This indication is approved under accelerated approval based on ORR and DOR; continued approval may be contingent on confirmatory trials.