On June 12, 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 who require systemic therapy and whose disease is radioactive iodine–refractory (if radioactive iodine is appropriate).
Selpercatinib received accelerated approval for this indication for patients aged 12 years and older in May 2020.
LIBRETTO-001
Efficacy was evaluated in LIBRETTO-001 (ClinicalTrials.gov identifier NCT03157128), a multicenter, open-label, muticohort clinical trial in 65 patients with RET fusion–positive thyroid cancer that was radioactive iodine–refractory (if radioactive iodine was an appropriate treatment option). Patients who were systemic therapy–naive and those who were previously treated were assigned to separate cohorts.
The major efficacy outcome measures in the trial were overall response rate and duration of response. The overall response rate was 85% (95% confidence interval [CI] = 71%–94%) in the 41 previously treated patients and 96% (95% CI = 79%–100%) in the 24 systemic therapy–naive patients. Median duration of response was 26.7 months (95% CI = 12.1 months to not evaluable) in the previously treated patients and not evaluable (95% CI = 42.8 months to not evaluable) in the systemic therapy–naive patients.
LIBRETTO-121
Supportive evidence included overall response and duration of response data from 10 pediatric and young adult patients with RET fusion–positive thyroid cancer treated in Study 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 overall response rate was 60% (95% CI = 26%–88%), and 83% of patients had an observed duration of response of ≥ 12 months.
The most common adverse reactions (≥ 25%) in patients receiving selpercatinib were edema, diarrhea, fatigue, dry mouth, hypertension, abdominal pain, constipation, rash, nausea, and headache. The most common grade 3 or 4 laboratory abnormalities (≥ 5%) were decreased lymphocytes, increased alanine aminotransferase, increased aspartate aminotransferase, 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 12 years of age and older.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. In addition, this application was granted Breakthrough Therapy designation and Orphan Drug designation.
