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

Clinical Summary: 

• The FDA granted traditional approval to selpercatinib based on findings from the multicenter, open-label LIBRETTO-001 trial, with supportive efficacy data from the pediatric LIBRETTO-121 study.

• Among patients with RET fusion-positive solid tumors other than non–small cell lung cancer and thyroid cancer, selpercatinib achieved an objective response rate of 47% with a median duration of response of 24.5 months. Responses were observed across multiple tumor types.

• This approval converts the previous accelerated approval to traditional approval and reinforces selpercatinib as a tissue-agnostic treatment option for adults and children with previously treated RET fusion-positive solid tumors.

On July 14, 2026, the US Food and Drug Administration (FDA) granted traditional approval to selpercatinib (Retevmo; Eli Lilly and Company) for adults and pediatric patients 2 years of age and older with locally advanced or metastatic RET fusion-positive solid tumors that have progressed following prior systemic therapy or for whom no satisfactory alternative treatment options exist. This action converts the accelerated approval granted for adults in 2022 and pediatric patients in 2024 to traditional approval.

The approval was supported by findings from the multicenter, open-label LIBRETTO-001 trial and additional efficacy data from the pediatric LIBRETTO-121 study.

In LIBRETTO-001, efficacy was evaluated in 75 patients with RET fusion-positive solid tumors other than non–small cell lung cancer (NSCLC) and thyroid cancer whose disease had progressed following prior systemic therapy or for whom no satisfactory alternative treatment options were available. The primary efficacy end points were objective response rate (ORR) and duration of response.

Selpercatinib achieved an ORR of 47%, with a median duration of response of 24.5 months. Responses were observed across multiple tumor types, including colorectal, pancreatic, salivary gland, soft tissue sarcoma, cholangiocarcinoma, breast, ovarian, neuroendocrine, small intestine, bronchial carcinoid, carcinoma of unknown primary, and skin cancers.

Supporting pediatric efficacy was demonstrated in the multicenter, open-label LIBRETTO-121 trial, which enrolled children and young adults with locally advanced RET fusion-positive solid tumors that were refractory to available therapies or lacked a standard curative systemic treatment option. Responses were observed in patients with congenital infantile fibrosarcoma, spindle cell sarcoma, and RET fusion-positive thyroid cancer.

For adults and adolescents 12 years of age and older, the recommended dose is 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. Recommended dosing for children aged 2 to younger than 12 years is provided in the prescribing information.

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

Source: 

US Food and Drug Administration. FDA grants traditional approval to selpercatinib for locally advanced or metastatic RET fusion-positive solid tumors. Accessed on July 14, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-traditional-approval-selpercatinib-locally-advanced-or-metastatic-ret-fusion-positive