Lilly Presents Updated Data on Retevmo in Advanced RET Fusion-Positive NSCLC

Clinical data from phase 1/2 LIBRETTO trial show evidence of meaningful clinical outcomes for patients, including those with difficult-to-treat brain metastases.

Eli and Lilly and Company announced updated data from the phase 1/2 LIBERETTO-001 trial of selpercatinib (Retevmo) in the 40- and 80-mg capsules dosages for individuals with metastatic rearranged during transfection (RET) fusion-positive non­–small cell lung cancer (NSCLC).

Selpercatinib is a selective and potent RET kinase inhibitor that is approved in multiple countries, including the United States.

The indications include the treatment of adult individuals with metastatic rearranged during transfection fusion-positive NSCLC and the treatment of individuals who aged 12 years or older with advanced or metastatic RET-mutant medullary thyroid cancer who require systemic therapy and who are radioactive iodine-refractory, if appropriate.

The updated data were presented at the 2022 European Lung Cancer Congress.

“The LIBRETTO trial provides the largest set of clinical data for a RET inhibitor, and these results continue to demonstrate evidence of meaningful clinical outcomes for patients with metastatic RET fusion-positive NSCLC treated with Retevmo, including those with difficult-to-treat brain metastases,” David Hyman, MD chief medical officer of oncology at Lilly, said in a statement. “We are continuing to build on the robust body of evidence supporting Retevmo, including through an ongoing randomized phase 3 confirmatory study, with a planned readout in 2023.”

The updated analysis had a cutoff date of June 15, 2021, and included 355 individuals who were eligible for efficacy analysis, 247 of whom were previously treated with at least 1 line of platinum chemotherapy and 69 individuals who were treatment-naïve.

The individuals who were previously treated with at least 1 line of platinum chemotherapy received a median of 2 prior treatment regimens, with approximately 58% receiving anti-programmed cell death protein 1 or anti-programmed death-ligand 1 therapy.

Responses were based on the independent review committee assessment.

Among the 274 individuals previously treated with a platinum chemotherapy, the confirmed objective response rate (ORR) was 61.1%, and the confirmed ORR was 84.1% among the treatment-naïve.

Additionally, 26 individuals had measurable central nervous system (CNS) metastases at baseline, and treatment with selpercatinib resulted in CNS ORR of approximately 84.6%, with 22 individuals having a confirmed best response of complete response or partial response.

Furthermore, at the median follow up of approximately 2 years in both the platinum-chemotherapy pretreated and treatment-naïve populations, the median duration of response was approximately 28.6 and 20.2 months, respectively.

The median progression free survival (PFS) was estimated at approximately 22 and 24.9 months, respectively.

Of the 26 individuals with measurable CNS disease, selpercatinib treatment resulted in a median intracranial PFS of 19.4 months.

The safety profile was consistent with the known safety profile of selpercatinib. The most common adverse events (AEs) were constipation, diarrhea, dry mouth, fatigue, hypertension, headache, increased alanine aminotransferase/aspartate aminotransferase, peripheral edema, and rash.

Approximately 10% of individuals discontinued taking the medication, because to AEs, and approximately 3% of them were deemed related to the drug.

A phase 3 trial is recruiting and will compare treatment with selpercatinib to the standard of care in the first-line treatment of advanced or metastatic RET fusion-positive NSCLC.

Reference

Lilly presents updated fata on Retevmo (selpercatinib) in advanced RET fusion-positive non–small-cell lung cancer (NSCLC) at the 2022 European Lung Cancer Congress. Lilly. News release. April 1, 2022. Accessed April 11, 2022. https://investor.lilly.com/news-releases/news-release-details/lilly-presents-updated-data-retevmor-selpercatinib-advanced-ret