On 29 2024, the US Food and Drug Administration (FDA) granted accelerated approval to selpercatinib (Retevmo, Eli Lilly and Company) for paediatric patients two years of age and older with:
- advanced or metastatic medullary thyroid cancer (MTC) with a RET mutation, 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); and
- locally advanced or metastatic solid tumours 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.
This is the first FDA approval of a targeted therapy for paediatric patients < 12 years of age with RET alterations. Selpercatinib was previously granted accelerated approval for the thyroid cancer indications in adults and paediatric patients 12 years of age and older. It also was previously granted accelerated approval for the solid tumour indication in adults.
Efficacy in paediatric and young adult patients was evaluated in LIBRETTO-121 (NCT03899792), an international, single-arm, multi-cohort study. Patients received selpercatinib, 92 mg/m2 orally twice daily, until disease progression, unacceptable toxicity, or other reason for treatment discontinuation. The primary efficacy population included 25 patients ages 2 to 20 with locally advanced or metastatic RET-activated solid tumours non-responsive 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 v1.1), as determined by blinded independent review committee was 48% (95% confidence interval [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 paediatric and young adult patients with RET-mutated 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 (≥25%) were musculoskeletal pain, diarrhoea, headache, nausea, vomiting, coronavirus infection, abdominal pain, fatigue, pyrexia, and haemorrhage. The most common Grade 3 or 4 laboratory abnormalities (≥5%) were decreased calcium, decreased haemoglobin, and decreased neutrophils.
The recommended selpercatinib dose for paediatric patients 2 to less than 12 years of age is based on body surface area. It is based on weight for patients 12 years of age and older.
LIBRETTO-121 was conducted as part of a paediatric Written Request under the Best Pharmaceuticals for Children Act.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
This application was granted priority review and orphan drug designation.
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For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact FDA’s Oncology Center of Excellence Project Facilitate.