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:<\/p>\n
This is the first FDA approval of a targeted therapy for paediatric patients < 12 years of age with RET<\/em> alterations. Selpercatinib was previously granted<\/a> accelerated approval for the thyroid cancer indications in adults and paediatric patients 12 years of age and older. It also was previously granted<\/a> accelerated approval for the solid tumour indication in adults.<\/p>\n 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 <\/sup>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<\/em>-activated solid tumours non-responsive to available therapies or with no standard systemic curative therapy available.<\/p>\n 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<\/em>-mutated MTC (n=14; ORR 43% [95% CI 18%, 71%]) and RET<\/em> fusion-positive thyroid cancer (n=10; ORR 60% [95% CI 26%, 88%]).<\/p>\n The most common adverse reactions (\u226525%) were musculoskeletal pain, diarrhoea, headache, nausea, vomiting, coronavirus infection, abdominal pain, fatigue, pyrexia, and haemorrhage. The most common Grade 3 or 4 laboratory abnormalities (\u22655%) were decreased calcium, decreased haemoglobin, and decreased neutrophils.<\/p>\n 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.<\/p>\n LIBRETTO-121 was conducted as part of a paediatric Written Request under the Best Pharmaceuticals for Children Act.<\/p>\n This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA\u2019s assessment.<\/p>\n This application was granted priority review and orphan drug designation.<\/p>\n Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA\u2019s MedWatch Reporting System.<\/p>\n For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact FDA\u2019s Oncology Center of Excellence<\/a> Project Facilitate<\/a>.<\/p>\n