On May 29, 2024, the U.S. Food and Drug Administration (FDA) granted accelerated approval to selpercatinib (Retevmo®) for pediatric patients aged 2 and older with either:

  • Advanced or metastatic medullary thyroid cancer (MTC) with a RET variant, as detected by an FDA-approved test, who require systemic therapy
  • Advanced or metastatic thyroid cancer with a RET gene fusion, as detected by an FDA-approved test, who require systemic therapy and who are radioactive iodine–refractory (if radioactive iodine is appropriate)
  • Locally advanced or metastatic solid tumors with a RET gene fusion, as detected by an FDA-approved test, that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options.
FDA update

This is the first FDA approval of a targeted therapy for pediatric patients younger than 12 with RET alterations. Selpercatinib was previously granted accelerated approval for the thyroid cancer indications in adults and pediatric patients aged 12 and older and for the solid tumor indication in adults.

Efficacy in pediatric and young adult patients was evaluated in LIBRETTO-121 (NCT03899792), an international, single-arm, multicohort trial. Patients received selpercatinib, 92 mg/m2 orally twice daily, until patients experienced disease progression, unacceptable toxicity, or another reason for treatment discontinuation. The primary efficacy population included 25 patients aged 2–20 with locally advanced or metastatic RET-activated solid tumors nonresponsive to available therapies or with no standard systemic curative therapy available.

The major efficacy outcome measures were confirmed overall response rate (ORR) and duration of response (DOR). The confirmed ORR (RECIST 1.1), as determined by blinded independent review committee, was 48% (95% CI = 28, 69). The median DOR was not reached (95% CI = not evaluable [NE], NE), with 92% of responders remaining in response at 12 months. Durable responses were observed in pediatric and young adult patients with RET-variant MTC (n = 14; ORR = 43% [95% CI = 18%, 71%]) and RET fusion-positive thyroid cancer (n = 10; ORR = 60% [95% CI = 26%, 88%]).

The most common adverse reactions reported in at least 25% of patients were musculoskeletal pain, diarrhea, headache, nausea, vomiting, coronavirus infection, abdominal pain, fatigue, pyrexia, and hemorrhage. The most common grade 3 or 4 laboratory abnormalities reported in at least 5% of patients were decreased calcium, decreased hemoglobin, and decreased neutrophils.

The recommended selpercatinib dose for pediatric patients aged 2 to less than 12 years is based on body surface area. It is based on weight for patients aged 12 and older. See the full prescribing information for specific dosing information.

LIBRETTO-121 was conducted as part of a pediatric written request under the Best Pharmaceuticals for Children Act. The applicant used the Assessment Aid to facilitate the FDA’s assessment. The application was granted priority review 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 800-FDA-1088.

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