FDA grants accelerated approval to selpercatinib for pediatric patients two years and older with RET-altered metastatic thyroid cancer or solid tumors

Regulatory approval: On May 29, 2024, the FDA granted accelerated approval to selpercatinib (Retevmo) for pediatric patients ≥2 years with specified RET-altered advanced/metastatic thyroid cancers and RET fusion–positive solid tumors. The decision was supported by the single-arm LIBRETTO-121 trial (NCT03899792), which reported a confirmed ORR of 48% (95% CI, 28–69) in the primary efficacy population, with median DOR not reached. This expands prior accelerated approvals that included adults and patients ≥12 years.

FDA accelerated approval (May 29, 2024): selpercatinib in pediatric RET-altered cancers

On May 29, 2024, the FDA granted accelerated approval to selpercatinib (Retevmo; Eli Lilly and Company) for pediatric patients aged ≥2 years with:

  • Advanced/metastatic medullary thyroid cancer (MTC) with a RET mutation (FDA-approved test) who require systemic therapy.
  • Advanced/metastatic thyroid cancer with a RET gene fusion (FDA-approved test) who require systemic therapy and are radioactive iodine–refractory (if RAI is appropriate).
  • Locally advanced/metastatic solid tumors with a RET gene fusion (FDA-approved test) that have progressed on/after prior systemic therapy or have no satisfactory alternative options.

This is reported as the first FDA approval of a targeted therapy for pediatric patients <12 years with RET alterations. Selpercatinib previously had accelerated approvals for certain thyroid cancer indications in adults and patients ≥12 years, and for the solid tumor indication in adults.

Supporting evidence

Efficacy and safety in pediatric/young adult patients were evaluated in LIBRETTO-121 (NCT03899792), an international, single-arm, multi-cohort trial using selpercatinib 92 mg/m² orally twice daily.

In the primary efficacy population (n=25; ages 2–20; locally advanced/metastatic RET-activated solid tumors), confirmed ORR was 48% (95% CI, 28–69) and median DOR was not reached (95% CI, NE–NE); 92% of responders remained in response at 12 months. Reported subgroup ORRs included 43% in RET-mutant MTC (n=14) and 60% in RET fusion–positive thyroid cancer (n=10).

Common adverse reactions (≥25%) included musculoskeletal pain, diarrhea, headache, nausea/vomiting, coronavirus infection, abdominal pain, fatigue, pyrexia, and hemorrhage.

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