On September 21, 2022, the FDA accelerated the approval of selpercatinib (Retevmo; Eli Lilly), a selective RET kinase inhibitor, for the treatment of all locally advanced or metastatic solid tumors with a RET gene fusion in patients whose disease progressed during or after systemic treatment or who have no alternative treatment options.
On the same day, the FDA granted regular full approval to selpercatinib for the treatment of locally advanced or metastatic non–small-cell lung cancer (NSCLC) and RET fusion, as detected by an FDA-approved test, following the FDA’s accelerated approval of this indication on May 8, 2020. Selpercatinib had been previously approved for advanced or metastatic RET-positive thyroid cancer and medullary thyroid cancer.
Also on September 21, the FDA approved the Oncomine Dx Target Test as a companion diagnostic for selpercatinib.
The tumor-agnostic approval of selpercatinib was based on results of the multicenter, multicohort, open-label LIBRETTO-001 clinical trial in 41 patients with RET-positive solid tumors (excluding NSCLC and thyroid cancer) whose disease progressed during or after systemic therapy or who had no alternative treatment options.
“FDA approval of the tumor-agnostic indication underscore[s] the importance of routine, comprehensive genomic testing for patients across a wide variety of tumor types,” said Vivek Subbiah, MD, M.D. Anderson Cancer Center, and a study coinvestigator.
The primary end points of LIBRETTO-001 were overall response rate (ORR) and duration of response (DOR). For the solid-tumor indication, the ORR was 44% (95% confidence interval [CI], 28-60) with selpercatinib and the DOR was 24.5 months (95% CI, 9.2-not estimable). The tumor types showing responses included pancreatic adenocarcinoma, soft-tissue sarcoma, bronchial carcinoid, cholangiocarcinoma, and colorectal, salivary, breast, ovarian, small intestine, and unknown primary cancers.
The initial approval of selpercatinib for NSCLC was based on results of 144 patients with NSCLC and RET fusion in the LIBRETTO-001 study. The conversion to full approval was based on data for an additional 172 patients, for a total of efficacy data for 316 patients with RET-positive NSCLC. Of 69 treatment-naïve patients with RET-positive NSCLC, the ORR with selpercatinib was 84% (95% CI, 73-92) and the DOR was 20.2 months (95% CI, 13-not estimable). Of 247 patients who had previously received chemotherapy, the ORR with selpercatinib was 61% (95% CI, 55-67) and the DOR was 28.6 months (95% CI, 20-not estimable).
The most common (≥25%) adverse reactions included edema, diarrhea, fatigue, dry mouth, hypertension, abdominal pain, constipation, rash, nausea, and headache.