FDA Approval Summary: Selpercatinib for the Treatment of Advanced RET Fusion-Positive Solid Tumors

by Selleckchem | Aug 26 2023

On September 21, 2022, the FDA granted accelerated approval to selpercatinib (Retevmo, Eli Lilly and Company) for the treatment of adult patients with locally advanced or metastatic solid tumors with a rearranged during transfection (RET) gene fusion that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options. The approval was based on data from Study LOXO-RET-17001 (LIBRETTO-001; NCT03157128), an international, non-randomized, multi-cohort clinical trial that included patients with advanced solid tumors harboring RET alterations. The overall response rate in 41 patients with locally advanced or metastatic RET fusion-positive solid tumors other than non-small cell lung cancer (NSCLC) or thyroid cancer was 44% [95% confidence interval (CI), 28%-60%], with median duration of response 24.5 months (95% CI, 9.2-not evaluable). Patients with 10 of 14 tumor types with a variety of fusion partners had objective responses, including patients with the following tumors: pancreatic adenocarcinoma, colorectal, salivary, unknown primary, breast, soft-tissue sarcoma, bronchial carcinoid, ovarian, small intestine, and cholangiocarcinoma. The recommendation for approval was supported by results from LIBRETTO-001 in patients with RET fusion-positive NSCLC and thyroid cancer, which formed the basis of prior approvals in these tumor types. The most common adverse reactions (>25%) were edema, diarrhea, fatigue, dry mouth, hypertension, abdominal pain, constipation, rash, nausea, and headache. This is the first tissue-agnostic approval of a RET-directed targeted therapy.

Comments:

That's correct! On September 21, 2022, the U.S. Food and Drug Administration (FDA) granted accelerated approval to selpercatinib, also known as Retevmo and developed by Eli Lilly and Company. This approval was specifically for the treatment of adult patients who have locally advanced or metastatic solid tumors with a rearranged during transfection (RET) gene fusion. The approval was based on data from a clinical trial called Study LOXO-RET-17001 (LIBRETTO-001; NCT03157128), which involved patients with various types of advanced solid tumors harboring RET alterations.

In the study, a total of 41 patients with locally advanced or metastatic RET fusion-positive solid tumors, excluding non-small cell lung cancer (NSCLC) and thyroid cancer, were evaluated. The overall response rate in this group was found to be 44%, with a 95% confidence interval ranging from 28% to 60%. The median duration of response was determined to be 24.5 months, with a confidence interval of 9.2 months to not evaluable. Notably, objective responses were observed in patients with various tumor types, including pancreatic adenocarcinoma, colorectal cancer, salivary cancer, unknown primary cancer, breast cancer, soft-tissue sarcoma, bronchial carcinoid, ovarian cancer, small intestine cancer, and cholangiocarcinoma.

It's important to note that the recommendation for approval of selpercatinib was also supported by the results from LIBRETTO-001 in patients with RET fusion-positive NSCLC and thyroid cancer, which had already received prior approvals for this therapy.

The most commonly reported adverse reactions, occurring in more than 25% of patients, were edema (fluid retention), diarrhea, fatigue, dry mouth, hypertension (high blood pressure), abdominal pain, constipation, rash, nausea, and headache.

This approval is significant as it marks the first tissue-agnostic approval of a targeted therapy directed towards RET alterations.