On June 12, 2024, the U.S. Food and Drug Administration (FDA) granted traditional approval to selpercatinib (Retevmo®) for adult and pediatric patients aged 2 years and older with advanced or metastatic RET fusion–positive thyroid cancer that requires systemic therapy but is refractory to radioactive iodine (RAI), if RAI is appropriate.
Selpercatinib received accelerated approval for the indication for patients aged 12 years and older in 2020.
Efficacy was evaluated in LIBRETTO-001 (NCT03157128), a multicenter, open-label, muticohort clinical trial in 65 patients with RET fusion–positive thyroid cancer. Participants were divided into an RAI-refractory (if RAI was an appropriate treatment option) and systemic therapy–naïve cohort (n = 24) and patients who were previously treated (n = 41), in separate cohorts.
The major efficacy outcome measures were overall response rate (ORR) and duration of response (DOR). The ORR was 85% (95% CI = 71%, 94%) in the previously treated patients and 96% (95% CI = 79%, 100%) in the systemic therapy–naïve patients. Median DOR was 26.7 months (95% CI = 12.1, not evaluable [NE]) in the previously treated patients and NE (95% CI = 42.8, NE) in the systemic therapy–naïve patients.
Supportive evidence included ORR and DOR data from 10 pediatric and young adult patients with RET fusion–positive thyroid cancer treated in LIBRETTO-121 (J2G-OX-JZJJ; NCT03899792), an international, single-arm, multicohort clinical trial of selpercatinib in pediatric and young adult patients with advanced RET-altered solid tumors. The ORR was 60% (95% CI = 26%, 88%), and 83% had an observed duration of response of at least 12 months.
In the drug’s clinical trials, the most common adverse reactions reported in at least 25% of patients were edema, diarrhea, fatigue, dry mouth, hypertension, abdominal pain, constipation, rash, nausea, and headache. The most common grade 3 or 4 laboratory abnormalities reported in at least 5% of patients were decreased lymphocytes, increased ALT and AST, decreased sodium, and decreased calcium.
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 years and older. See the prescribing information for specific dosing information.
The applicant used the Assessment Aid to facilitate FDA’s review. FDA granted the application breakthrough designation and orphan drug designation. FDA’s 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 applications for investigational oncology products, healthcare professionals may contact the Oncology Center of Excellence’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.