Selpercatinib cleared for RET fusion-positive solid tumors

On July 14, 2026, the Food and Drug Administration granted traditional approval to selpercatinib (Retevmo, Eli Lilly and Company) for adult and pediatric patients two years of age and older with locally advanced or metastatic solid tumors with a RET gene fusion, as detected by an FDA-approved test, that have 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 two years of age and older in 2024.

Full prescribing information for Retevmo will be posted on Drugs@FDA.

Efficacy and Safety

Efficacy was evaluated in a multicenter, open-label, multi-cohort trial (LIBRETTO-001, 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 (ORR) and duration of response (DOR). ORR was 47% (95% CI: 35, 59), with a median DOR of 24.5 months (95% CI: 11.2, 49.1). 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 12 years of age 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 two to less than 12 years of age.

This review used the Assessment Aid, a voluntary submission from the applicant to facilitate FDA’s assessment. The FDA approved this application two months ahead of the FDA goal date.

Selpercatinib received orphan drug designation for the tissue agnostic indication. A description of FDA expedited programs is 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 1-800-FDA-1088.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.

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