FDA Expands Pediatric Indication for Entrectinib and Approves New Pellet Formulation

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On October 20, the U.S. Food and Drug Administration (FDA) granted accelerated approval to the small-molecule tyrosine kinase inhibitor entrectinib (Rozlytrek) for pediatric patients aged 1 month and older with solid tumors that have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion without a known acquired resistance mutation that are metastatic or where surgical resection is likely to result in severe morbidity, and have progressed following treatment or have no satisfactory standard therapy. In August 2019, the FDA granted accelerated approval to entrectinib for pediatric patients aged 12 years and older for this indication.

The FDA also approved a new oral pellet formulation for entrectinib, and the prescribing information now includes instructions for making an oral suspension from the capsules.


Efficacy in NTRK fusion–positive tumors was investigated in 33 pediatric patients who received entrectinib based on body surface area (20 mg to 600 mg orally or via enteral feeding tube once daily) in one of two multicenter, single-arm clinical trials: STARTRK-NG ( identifier NCT02650401) or TAPISTRY (NCT04589845). Identification of positive NTRK gene fusion status was determined in local laboratories or a central laboratory using nucleic acid–based tests prior to enrollment.

The major efficacy outcome measure was overall response rate as assessed by blinded independent central review according to Response Evaluation Criteria in Solid Tumors version 1.1 for extracranial tumors, and Response Assessment in Neuro-Oncology for primary central nervous system tumors. An additional efficacy outcome measure was duration of response.

Among 33 pediatric patients, the overall response rate was 70% (95% confidence interval [CI] = 51%–84%) and median duration of response was 25.4 months (95% CI = 14.3 months to not evaluable). The most common cancers seen in patients in the trials were primary central nervous system tumors and infantile fibrosarcoma. 

In the pooled safety population of pediatric patients receiving entrectinib (n = 76), the most common (≥ 20%) adverse reactions were 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.

The recommended dose for pediatric patients aged > 1 month to ≤ 6 months is 250 mg/m2 orally once daily. The recommended dose for pediatric patients aged > 6 months is based on body surface area (up to a maximum of 600 mg once daily).

This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. This application was granted Priority Review, Breakthrough Therapy designation, and Orphan Drug designation.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.