FDA Approves Entrectinib for Pediatric Solid Tumors

The approval is based on 2 multicenter, single-arm trials: the phase 1/2 STARTRK-NG study (NCT02650401), and the phase 2 TAPISTRY study (NCT04589845).

Entrectinib (Rozlytrek) has been given accelerated approval by the FDA for pediatric patients who are 1 month or older with solid tumors, according to a press release from the organization.¹

The indication includes patients with NTRK gene fusions without a known acquired resistance mutation, metastatic disease or where surgical resection is likely to result in severe morbidity, and progression following treatment or those who have no satisfactory standard therapy.

The approval is based on 2 multicenter, single-arm trials: the phase 1/2 STARTRK-NG study (NCT02650401), and the phase 2 TAPISTRY study (NCT04589845). A total of 33 patients were enrolled between both trials with dosing based on body surface area of 20 mg to 600 mg given orally or through an enteral feeding tube once daily.

Investigators aimed to assess the overall response rate (ORR) as analyzed by blinded independent central review via RECIST 1.1 criteria for extracranial tumors and the Response Assessment in Neuro-Oncology (RANO) for primary central nervous system (CNS) tumors. The ORR was 70% (95% CI, 51%-84%), and the median duration of response was 25.4 months (95% CI, 14.3-not evaluable).

Patients were most commonly diagnosed with primary CNS tumors and infantile fibrosarcoma. The most common adverse effects included pyrexia, constipation, increased weight, vomiting, diarrhea, and nausea.

For patients who are older than 1 month and 6 months or younger, the recommend dose is 250 mg/m2 orally once daily. For those older than 6 months, the dose is based on body surface area and can be given up to 600 mg once daily.

In August 2019, entrectinib was granted accelerated approval for patients 12 years and older based on the same indication as well as patients with non–small cell lung cancer who have ROS1-positive tumors.²

References

1. FDA expands pediatric indication for entrectinib and approves new pellet formulation. News release. FDA. October 20, 2023. Accessed October 20, 2023. https://bit.ly/46Dpqtv
2. FDA approves entrectinib for NTRK solid tumors and ROS-1 NSCLC. News release. FDA. August 15, 2019. Accessed October 20, 2023. https://bit.ly/46PA8Nc