FDA Grants Accelerated Approval of Retevmo for Tumor Agnostic RET Gene Fusions

The FDA has granted accelerated approval to Lilly’s Retevmo (selpercatinib) for adult patients with RET gene fusion. Tumor-agnostic data supporting approval demonstrated an overall response rate (ORR) of 44% across multiple tumor types in patients who have progressed on or following prior systemic treatment.

This indication is approved under accelerated approval based on ORR and duration of response (DOR). Continued approval for this indication is contingent upon verification of clinical benefit in a confirmatory trial.

The FDA also granted traditional approval of Retevmo to treat adults with locally advanced or metastatic non-small cell lung cancer (NSCLC) with a RET gene fusion. This broadens the Retevmo label to include patients with locally advanced disease and converts the May 2020 accelerated approval for NSCLC to a traditional approval.

The two approvals are supported by data from the pivotal LIBRETTO-001 trial, which is the largest clinical trial of patients with RET-driven cancers treated with a RET inhibitor. The multicenter, open-label, multi-cohort study enrolled patients with locally advanced or metastatic RET-driven solid tumors, including NSCLC. Major efficacy outcomes were ORR and DOR.

Vivek Subbiah, M.D.

“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,” co-investigator for LIBRETTO-001 Vivek Subbiah, M.D., associate professor of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center, said in a press release. “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 this phase1/2 trial, among the 41 patients in the tumor-agnostic data set, the most common cancers were pancreatic adenocarcinoma, colorectal, salivary and unknown primary (7%). Thirty-seven patients received prior systemic therapy. Among the 11 patients with pancreatic adenocarcinoma, the overall response rate was 55%; among the 10 patients with colorectal cancer, the overall response rate was 20%; among those four patients with salivary cancer, two achieved overall response.

In the arm with 69 patients with NSCLC, the overall response rate was 84% and the median duration of response was 20.2 months.

In the full safety population of 796 patients with advanced solid tumors, the most common adverse reactions were edema, diarrhea, fatigue, dry mouth, hypertension, abdominal pain, constipation, rash, nausea, and headache.