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FDA Expands Pediatric Indication for Rozlytrek (entrectinib) and Approves New Pellet Formulation

On October 20, 2023, the Food and Drug Administration granted accelerated approval to entrectinib (Rozlytrek, Genentech Inc.) for pediatric patients older than 1 month with solid tumors that have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion without a known acquired resistance mutation, 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, FDA granted accelerated approval to entrectinib for pediatric patients 12 years of age and older for this indication.

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.

View full prescribing information for Rozlytrek.

Efficacy in NTRK-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 (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 (ORR), as assessed by Blinded Independent Central Review (BICR) according to RECIST v1.1 for extracranial tumors and Response Assessment in Neuro-Oncology (RANO) for primary central nervous system tumors. An additional efficacy outcome measure was duration of response (DOR). Among the 33 pediatric patients, the ORR was 70% (95% CI: 51, 84) and median DOR was 25.4 months (95% CI: 14.3, not evaluable). The most common cancers 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 > 1 month to ≤ 6 months of age is 250 mg/m2 orally once daily. The recommended dose for pediatric patients > 6 months is based on body surface area (up to a maximum of 600 mg once daily). See the prescribing information for specific dosing information.

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 designation and orphan drug designation. FDA expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.

Source: FDA

Posted: October 2023

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