Targeting a Gene Fusion in Solid Tumors 

The FDA granted accelerated approval to selpercatinib to treat solid tumors harboring RET gene fusions. 

The U.S. Food and Drug Administration (FDA) has granted accelerated approval to selpercatinib (Retevmo) for the treatment of adult patients with advanced or metastatic solid tumors with gene fusions involving the RET gene. Patients must have had disease progression on or following prior systemic therapy and should have no other satisfactory treatment options. 

Selpercatinib is in a class of drugs known as kinase inhibitors, which block certain cell signaling pathways that promote tumor growth. Selpercatinib blocks the kinase RET, which can become aberrantly activated or overexpressed in tumors due to a fusion between part of the RET gene and part of another gene. 

closeup of a cancer cell
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The approval was based on the multicenter, open-label, multi-cohort LIBRETTO-001 clinical trial, designed to test selpercatinib in patients with RET fusion-positive solid tumors. In a cohort of 41 patients with tumors other than non-small cell lung cancer (NSCLC) or thyroid cancer, the overall response rate was 44 percent, with a median response duration of 24.5 months. 

The most common cancers evaluated in this trial were pancreatic (27 percent), colorectal (24 percent), salivary gland (10 percent), and cancers of unknown primary (7 percent). Responses occurred in patients with pancreatic cancer, colorectal cancer, salivary gland cancer, cancer of unknown primary, breast cancer, soft tissue sarcoma, bronchial carcinoid tumor, ovarian cancer, small intestine cancer, and cholangiocarcinoma. 

An expansion cohort of LIBRETTO-001 was also used to grant full approval [LINK] to selpercatinib for the treatment of patients with RET fusion-positive NSCLC. 

RET fusions are estimated to occur in 1 to 2 percent of NSCLC tumors, around 20 percent of papillary thyroid tumors, and less than 1 percent of other solid tumor types. 

The FDA rendered its decision on September 21, 2022. Accelerated approval means that continued approval may be contingent upon a confirmatory trial.