On July 14, the U.S. Food and Drug Administration (FDA) granted traditional approval to selpercatinib (Retevmo), an oral RET inhibitor, for adult and pediatric patients aged 2 years and older with locally advanced or metastatic solid tumors with a RET gene fusion, as detected by an FDA-approved test, whose disease has progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options. Selpercatinib received accelerated approval for this indication for adult patients in 2022 and for pediatric patients aged 2 years and older in 2024.
LIBRETTO-001 and LIBRETTO-121
Efficacy was evaluated in a multicenter, open-label, multicohort trial (LIBRETTO-001, ClinicalTrials.gov identifier NCT03157128) and supported by results in RET fusion–positive non–small cell lung cancer (NSCLC) and RET fusion–positive thyroid cancer. Efficacy was evaluated in 75 patients with RET fusion–positive tumors other than NSCLC and thyroid cancer with disease progression on or following prior systemic treatment or who had no satisfactory alternative treatment options.
The major efficacy outcome measures were overall response rate and duration of response. The overall response rate was 47% (95% confidence interval [CI] = 35%–59%), with a median duration of response of 24.5 months (95% CI = 11.2–49.1 months). Tumor types with responses included colorectal, pancreatic adenocarcinoma, salivary, soft-tissue sarcoma, cholangiocarcinoma, carcinoma of the skin, unknown primary, breast, bronchial carcinoid, ovarian, small intestine, and neuroendocrine (including pancreatic).
Efficacy in pediatric and young adult patients was evaluated in LIBRETTO-121 (NCT03899792), a multicenter, open-label, multi-cohort trial. Efficacy was evaluated in patients with locally advanced refractory RET fusion–positive solid tumors who were unresponsive to available therapies or had no standard systemic curative therapy available. Responses were observed in one patient with congenital infantile fibrosarcoma, one patient with a spindle cell sarcoma, and in patients with RET fusion–positive thyroid cancer.
The prescribing information includes warnings and precautions for hepatotoxicity, interstitial lung disease/pneumonitis, hypertension, QT interval prolongation, hemorrhagic events, hypersensitivity, tumor lysis syndrome, risk of impaired wound healing, hypothyroidism, embryo-fetal toxicity, and slipped capital femoral epiphysis/slipped upper femoral epiphysis in pediatric patients.
Recommended Dosage
The recommended selpercatinib dose for adult and adolescent patients aged 12 years or older based on body weight is:
- Less than 50 kg: 120 mg orally twice daily
- 50 kg or greater: 160 mg orally twice daily
See the prescribing information for the recommended dose for pediatric patients aged 2 years to less than 12 years.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate FDA’s assessment. The FDA approved this application 2 months ahead of the FDA goal date.
Selpercatinib received Orphan Drug designation for the tissue-agnostic indication.
