FDA Grants Traditional Approval to Selpercatinib for RET Fusion-Positive Tumors

The FDA has granted traditional approval to selpercatinib (Retevmo) for adult and pediatric patients 2 years and older with locally advanced or metastatic solid tumors harboring a RET gene fusion, as identified by an FDA-approved test, whose disease has progressed on or after prior systemic therapy or who lack a satisfactory alternative treatment.¹ The action converts an accelerated approval granted in 2022 for adults and in 2024 for pediatric patients into full approval, following confirmatory data on response durability across a broad range of tumor types.^2,3

Selpercatinib is a selective RET tyrosine kinase inhibitor. Efficacy for this tissue-agnostic indication was established in LIBRETTO-001 (NCT03157128), a multicenter, open-label, multi-cohort trial, with supportive data drawn from cohorts of patients with RET fusion-positive non–small cell lung cancer (NSCLC) and thyroid cancer. For the current indication, the FDA evaluated 75 patients with RET fusion-positive tumors other than NSCLC or thyroid cancer whose disease had progressed on prior systemic treatment or who had no satisfactory alternative options.

The trial's major efficacy outcome measures were overall response rate (ORR) and duration of response (DOR). ORR was 47% (95% CI, 35%-59%), and median DOR was 24.5 months (95% CI, 11.2-49.1). Responses occurred across a wide array of histologies, including colorectal, pancreatic adenocarcinoma, salivary gland, soft tissue sarcoma, cholangiocarcinoma, cutaneous carcinoma, carcinoma of unknown primary, breast, bronchial carcinoid, ovarian, small intestine, and neuroendocrine tumors, including pancreatic neuroendocrine tumors.

Efficacy in pediatric and young adult patients was assessed in LIBRETTO-121 (NCT03899792), a multicenter, open-label, multi-cohort trial enrolling patients with locally advanced, refractory RET fusion-positive solid tumors who had no response to available therapies or no standard curative systemic option. Responses were reported in one patient with congenital infantile fibrosarcoma, one patient with spindle cell sarcoma, and in patients with RET fusion-positive thyroid cancer.

Safety Considerations

The prescribing information carries warnings and precautions for hepatotoxicity, interstitial lung disease/pneumonitis, hypertension, QT interval prolongation, hemorrhagic events, hypersensitivity reactions, tumor lysis syndrome, impaired wound healing, hypothyroidism, embryo-fetal toxicity, and, in pediatric patients, slipped capital femoral epiphysis (slipped upper femoral epiphysis). Clinicians should incorporate baseline and periodic monitoring—liver function tests, blood pressure, electrocardiograms, and thyroid function—into treatment plans consistent with the full label.

Dosing

For adult and adolescent patients 12 years of age or older, the recommended dose is weight-based: 120 mg orally twice daily for patients weighing less than 50 kg, and 160 mg orally twice daily for those weighing 50 kg or more. Dosing recommendations for pediatric patients 2 to younger than 12 years are detailed in the full prescribing information, which will be posted on Drugs@FDA.¹

The application was reviewed using the FDA's Assessment Aid, a voluntary submission tool from the applicant intended to streamline the agency's review, and was approved two months ahead of the FDA goal date. Selpercatinib previously received orphan drug designation for this tissue-agnostic indication.

REFERENCES

1. FDA grants traditional approval to selpercatinib for locally advanced or metastatic RET fusion-positive solid tumors. News release. US FDA. July 14, 2026. Accessed July 14, 2026. https://tinyurl.com/ym3hr6pj

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. New release. Eli Lily and Company. September 21, 2022. Accessed September 21, 2022. https://bit.ly/3Urz5xB

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 May 29, 2024. https://tinyurl.com/3ykektts