The FDA granted accelerated approval to selpercatinib (Retevmo) for adults with locally advanced or metastatic solid tumors associated with RET gene fusions, the agency announced on Wednesday.
Selpercatinib’s tumor-agnostic indication is specifically for patients who have progressed on or following systemic treatment, and for those who have no satisfactory alternative options. The RET inhibitor’s initial 2020 accelerated approval, which carried indications for locally advanced or metastatic non-small cell lung cancers (NSCLCs) and thyroid cancers associated with RET gene fusions, has been converted to a full approval, the agency announced.
Approvals were based on results from the LIBRETTO-001 trial, which enrolled patients with locally advanced or metastatic RET-driven solid tumors.
Among 41 patients in the tumor-agnostic set, the overall response rate was 44% (95% CI 28-60), with 4.9% achieving a complete response. Median duration of response was 24.5 months (95% CI 9.2-not estimable). Responses were observed in pancreatic, colorectal, ovarian, and breast cancers; in soft-tissue sarcoma, cholangiocarcinoma, and bronchial carcinoids; as well as in tumors of the salivary gland and small intestine.
The efficacy evaluation was further supported by data from the trial’s 343 patients with RET fusion-positive NSCLC and thyroid cancer.
“In the LIBRETTO-001 trial, selpercatinib demonstrated clinically meaningful and durable responses across a variety of tumor types in patients with RET-driven cancers, including pancreatic, colon, and other cancers in need of new treatment options,” said study investigator Vivek Subbiah, MD, of MD Anderson Cancer Center in Houston, in a statement from drugmaker Eli Lilly. “These data and FDA approval of the tumor-agnostic indication underscore the importance of routine, comprehensive genomic testing for patients across a wide variety of tumor types.”
In the full LIBRETTO-001 safety population, the most common adverse events with selpercatinib were edema, diarrhea, fatigue, dry mouth, hypertension, abdominal pain, constipation, rash, nausea, and headache. The most common grade 3/4 laboratory abnormalities were increases in alanine aminotransferase and aspartate aminotransferase, and decreases lymphocytes, sodium, and calcium.
The labeling for selpercatinib contains 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, and embryo-fetal toxicity.