The Food and Drug Administration (FDA) has granted accelerated approval to Retevmo® (selpercatinib) for adults 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 accelerated approval was based on overall response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
Additionally, the FDA granted traditional approval to Retevmo for adults with locally advanced or metastatic non-small cell lung cancer (NSCLC) with RET gene fusion, as detected by an FDA-approved test. Previously, the treatment was only approved for adults with metastatic RET fusion-positive NSCLC.
The 2 approvals were based on data from the pivotal multicenter, open-label, multicohort phase 1/2 LIBRETTO-001 trial (ClinicalTrials.gov Identifier: NCT03157128), which evaluated the efficacy and safety of selpercatinib, a selective RET kinase inhibitor, in patients with locally advanced or metastatic RETfusion-positive solid tumors, including NSCLC. The major efficacy outcome was ORR and DOR, as assessed by a blinded independent review committee.
Among the 41 patients with RET fusion-positive solid tumors, the ORR was 44% (95% CI, 28-60), of which 4.9% achieved complete response (CR) and 39% achieved partial response (PR). The median DOR was 24.5 months (95% CI, 9.2-not evaluable [NE]) and 67% had a DOR lasting at least 6 months.
“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 Vivek Subbiah, MD, associate professor of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center and co-investigator for LIBRETTO-001.
Among 247 patients with RET fusion-positive NSCLC who were previously treated with platinum chemotherapy, the ORR was 61% (95% CI, 55-67), of which 7.3% achieved CR and 54% achieved PR. The median DOR was 28.6 months (95% CI, 20-NE) and 63% had a DOR lasting at least 12 months. Moreover, according to an exploratory subgroup analysis, the ORR was 63% (95% CI, 54-70) and the median DOR was 28.6 months (95% CI, 14.8-NE) among 144 patients who received prior anti-PD-1 or anti-PD-L1 therapy either sequentially or concurrently with platinum-based chemotherapy.
Among 69 patients with treatment-naïve RET fusion-positive NSCLC, the ORR was 84% (95% CI, 73-92), of which 5.8% achieved CR and 78% achieved PR. The median DOR was 20.2 months (95% CI, 13-NE) and 50% had a DOR lasting at least 12 months.
As for safety, the most common adverse reactions with selpercatinib were edema, diarrhea, fatigue, dry mouth, hypertension, abdominal pain, constipation, rash, nausea, and headache. The most common grade 3 or 4 laboratory abnormalities were decreased lymphocytes, increased alanine aminotransferase, increased aspartate aminotransferase, decreased sodium, and decreased calcium.
Retevmo is available as 40mg capsules in 60-count bottles and 80mg capsules in 60- and 120-count bottles.
The Oncomine Dx Target (ODxT) Test (Thermo Fisher Scientific) has been approved as a companion diagnostic for selpercatinib.
- FDA approves Lilly’s Retevmo® (selpercatinib), the first and only RET inhibitor for adults with advanced or metastatic solid tumors with a RET gene fusion, regardless of type. News release. Eli Lilly and Company. Accessed September 22, 2022. https://www.prnewswire.com/news-releases/fda-approves-lillys-retevmo-selpercatinib-the-first-and-only-ret-inhibitor-for-adults-with-advanced-or-metastatic-solid-tumors-with-a-ret-gene-fusion-regardless-of-type-301630358.html
- Retevmo. Package insert. Eli Lilly and Company; 2022. Accessed September 21, 2022. https://pi.lilly.com/us/retevmo-uspi.pdf