FDA Approves Selpercatinib for Advanced, Metastatic Solid Tumors With RET Gene Fusion


Selpercatinib produced clinically meaningful and durable responses across a variety of tumor types in patients with RET-driven cancers.

Selpercatinib (Retevmo) was granted accelerated approval by the FDA for the treatment of adult patients with locally advanced or metastatic solid tumors harboring a RET gene fusion who progressed on or following prior systemic therapy or who have no satisfactory alternative treatment options. The approval was based on data from the phase 1/2 LIBRETTO-001 trial (NCT03157128), which enrolled 41 patients with RET fusion–positive tumors other than non–small cell lung cancer (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 trial co-investigator Vivek Subbiah, MD, associate professor of Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center, 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 LIBRETTO-001, RET fusions were detected in 97.6% of patients by leveraging next-generation sequencing, with 2.4% of these fusions identified using FISH. Selpercatinib produced an overall response rate (ORR) of 44% (95% CI, 28%-60%) in the all-comer patient population, 4.9% of patients achieved a complete response, and 39% achieved a partial response.

The median duration of response (DOR) with selpercatinib was 24.5 months (95% CI, 9.2–not evaluable). Further, 67% of patients experienced a response that lasted for at least 6 months. Selpercatinib produced responses across tumor types, including pancreatic adenocarcinoma, colorectal cancer (CRC), salivary, unknown primary, breast, soft tissue sarcoma, bronchial carcinoid, ovarian, small intestine, and cholangiocarcinoma.

Among 11 patients with pancreatic adenocarcinoma, selpercatinib produced an ORR of 55% (95% CI, 23%-83%), with a DOR from 2.5 months to 38.3+ months. Among 10 patients with CRC, selpercatinib produced an ORR of 20% (95% CI, 2.5%-56%) and a DOR that ranged from 5.6 months to 13.3 months.

The ORR was 50% (95% CI, 7%-93%) among patients with salivary cancer (n = 4), with a DOR that ranged from 5.7 months to 28.8+ months. Among 3 patients with unknown primary cancer, the ORR with selpercatinib was 33% (95% CI, 0.8%-91%), with a DOR of 9.2 months.

Across the entire efficacy patient population, the median age was 50 years (range, 21-85) and 54% were women, 68% of patients were White, 24% were Asian, 7% were Hispanic or Latino, and 4.9% were Black. ECOG performance status found that 95% had a status of 0 or 1 and 5% had a status of 2. Further, 95% of patients enrolled had metastatic disease and 90% of patients received prior systemic treatment, with a median of 2 prior lines administered (range, 0-9). Further, 32% of patients were administered 3 or more prior lines of treatment.

The most common adverse events experienced by at least 25% of patients included edema, diarrhea, fatigue, dry mouth, hypertension, abdominal pain, constipation, rash, nausea, and headache.

"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 a 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."


FDA approves selpercatinib for locally advanced or metastatic RET fusion-positive solid tumors. News release. FDA. September 21, 2022. Accessed September 21, 2022. https://bit.ly/3f8Wzr7

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