FDA Traditionally Approves Selpercatinib in RET+ Solid Tumors

The FDA has granted traditional approval to selpercatinib (Retevmo) for adult and pediatric patients 2 years of age and older with locally advanced or metastatic RET gene fusion-positive solid tumors who have progressed on or after prior systemic treatment, or who have no satisfactory alternative treatment options, according to a news release from the agency.¹

Previously, the FDA granted accelerated approval to selpercatinib for adults in this indication in September 2022, and pediatric patients 2 years and older in 2024.^2,3

The FDA’s decision was supported by results from the phase 1/2 LIBRETTO-001 (NCT03157128), which evaluated selpercatinib in patients with advanced solid tumors, including RET fusion-positive non-small cell lung cancer (NSCLC) and RET fusion-positive thyroid cancer. Seventy five patients with RET fusion positive tumors excluding NSCLC and thyroid cancer were also evaluated. Among all patients, the overall response rate (ORR) was 47% (95% CI, 35%-59%), with a median duration of response of 24.5 months (95% CI, 11.2-49.1).

Evaluated tumor types that demonstrated responses to treatment included colorectal, pancreatic adenocarcinoma, salivary, cholangiocarcinoma, soft tissue sarcoma, breast, ovarian, carcinoma of the skin, unknown primary, small intestine, bronchial carcinoid, and neuroendocrine.

In pediatric and young adult patients, the efficacy of selpercatinib was evaluated in the phase 1/2 LIBRETTO-121 trial (NCT03899792), which enrolled patients with locally advanced refractory RET fusion-positive solid tumors who did not respond to available therapies or had no standard systemic curative therapy available. One patient with congenital infantile fibrosarcoma and 1 patient with a spindle cell sarcoma demonstrated responses to treatment, in addition to patients with RET fusion-positive thyroid cancer.

The recommended dose of selpercatinib based on body weight is:

• 120 mg orally twice daily for patients less that 50 kg
• 160 mg orally twice daily for patients 50 kg or greater

The label for selpercatinib includes warnings and precautions for hepatotoxicity, interstitial lung disease/pneumonitis, hypertension, hemorrhagic events, hypersensitivity, QT interval prolongation, risk of impaired wound healing, hypothyroidism, tumor lysis syndrome, embryo-fetal toxicity, and slipped capital femoral epiphysis/slipped upper femoral epiphysis in pediatric patients.

References

1. FDA grants traditional approval to selpercatinib for locally advanced or metastatic RET fusion-positive solid tumors. News release. FDA. July 14, 2026. Accessed July 14, 2026. https://tinyurl.com/katfztfb
2. FDA approves Lilly's Retevmo® (selpercatinib), the first and only RET inhibitor for adults with advanced or metastatic solid tumors with a RET gene fusion, regardless of type. News release. Eli Lilly and Company. September 21, 2022. Accessed July 14, 2026. https://prn.to/3dFC8Bz
3. FDA grants accelerated approval to selpercatinib for pediatric patients two years and older with RET-altered metastatic thyroid cancer or solid tumors. News release. FDA. May 29, 2024. Accessed July 14, 2026. https://shorturl.at/4Bduj