FDA Approves Selpercatinib for Adults With RET Fusion+ Advanced/Metastatic Solid Tumors

Following a report of impressive 2-year follow-up data, the FDA has granted a regular approval to selpercatinib.

The FDA has granted regular approval to selpercatinib (Retevmo) 40 mg & 80 mg capsules for the treatment of adult patients with locally advanced or metastatic solid tumors with a RET gene fusion that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options.

According to an announcement by Eli Lilly and Company, the approval was granted based on finding from the LIBRETTO-001 clinical trial. As previously reported by Targeted Oncology™, robust and durable response were observed with selpercatinib in the study after more than 20 months of follow-up. Simultaneously, the FDA granted a traditional approval to selpercatinib for the treatment of adults with locally advanced or metastatic NSCLC with a RET gene fusion, as detected by an FDA-approved test.

"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, 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."

The phase 2 study included 316 patients with RET fusion-positive NSCLC were evaluated for 18 months or more. Sixty-four of the patients were treatment-naïve, and 247 were previously treated with chemotherapy.

The ORR By independent review committee (IRC) in the treatment-naïve population was 84% (95% CI, 73%-92%), with complete response (CRs) in 6% of patients. Partial responses (PRs) were observed in 78% of patients, while 9% had stable disease (SD), and 4% has progressive disease. The median DOR was 20.2 months (95% CI, 13.0 to not evaluated [NE]). Responses were ongoing in 40% of the treatment-naïve population at the time of data cutoff.

Selpercatinib achieved a median progression-free survival (PFS) of 22.0 months (95% CI, 13.8 to NE) in the treatment-naïve population. Thirty-five percent of these patents were alive and progression-free at a median follow-up of 21.9 months. The median overall survival (OS) was not estimable, but 69% (95% CI, 55%-80%) of treatment-naïve patients were alive at 2 years.

The ORR by IRC was 61% (95% CI, 55%-67%) in chemotherapy-pretreated patients with CRs in 7% of patients. PRs were seen in 54% of patients, 33% of patients had SD, and 3% had PD. The median DOR in the pretreated group was 28.6 months (95% CI, 20.4-NE).

The chemotherapy-pretreated group had a median PFS of 24.9 months (95% CI, 19.3-NE). Thirty-eight percent of patients remained alive and progression-free at a median follow-up of 24.7 months. OS was also not estimable in the pretreated group, but 69% (95% CI, 62%-75%) of patients were alive at 2 years.

In terms of safety, the most common grade 3 or higher treatment-emergent adverse events (AEs) were hypertension (19.7%), alanine aminotransferase increase (ALT; 11.4%), aspartate aminotransferase increase (AST; 8.8%), diarrhea (5.0%), and electrocardiogram QT prolongation (4.8%). Grade 3 or higher treatment-related AEs that occurred most commonly included hypertension (13.2%), AST increase (6.3%), and ALT increase (9.0%).

"Since its initial accelerated approval, Retevmo has shifted the treatment paradigm for patients with RET-altered cancers," said David Hyman, MD, chief medical officer, Loxo@Lilly, in the press release. "Retevmo is the first and only RET inhibitor to receive both tumor-agnostic accelerated approval and traditional approval in NSCLC, further supporting its ability to deliver meaningful clinical benefit for patients across diverse tumor types."


1. 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. New release. Eli Lily and Company. September 21, 2022. Accessed September 21, 2022. https://bit.ly/3Urz5xB

2. Drilon A, Subbiah V, Gautschi O, et al. Selpercatinib in patients with RET fusion–positive non–small-cell lung cancer: updated safety and efficacy from the registrational libretto-001 phase I/II trial.Published September 19, 2022. J Clin Oncol. doi:10.1200/JCO.22.00393

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