The FDA has granted regular approval selpercatinib (Retevmo®, Eli Lilly and Company) for treatment of adult patients with locally advanced or metastatic rearranged during transfection (RET) gene fusion non-small cell lung cancer (NSCLC). Selpercatinib previously received an accelerated approval from the FDA based on its initial trial results in May 2020. This comes in combination with an FDA approval of the Oncomine Dx Target (ODxT) Test (Thermo Fisher Scientific) as a companion diagnostic for selpercatinib.
"Selpercatinib (formerly known as LOXO-292) is a novel, ATP-competitive, highly selective small-molecule inhibitor of RET kinase," wrote Alexander Drilon, MD, Medical Oncologist at Memorial Sloan Kettering Cancer Center, and colleagues, in their publication of the Libretto-001 trial (NCT03157128), on which approval was based. "Experimental models showed that it has nanomolar potency against diverse RET alterations, including fusions, activating point mutations, and predicted acquired resistance mutations, while mainly sparing non-RET kinases and non-kinase targets."
Maximum tolerated dose, safety, and efficacy were measured in 316 patients in the phase 1/2, open-label, multi-cohort, multicenter trial for selpercatinib. During phase 1, enrolled patients were administered selpercatinib orally once or twice daily in capsule or liquid form, in dosages ranging between 20 mg once daily and 240 mg twice daily. For patients being enrolled in phase 2, they were given 160 mg of selpercatinib twice daily. Treatment continued on a 28-day cycle until disease progression or unacceptable toxicity.
The primary end points measured were overall response rate and duration of response, determined by Blind Independent Review Committee (BIRC). Sixty-nine patients who were treatment-naive saw a significant median overall response rate of 84% and median duration of response of 20.2 months. As for the remaining 247 patients previously treated with platinum-based chemotherapy, the median overall response rate was 61% and median duration of response was 28.6 months.
The most common adverse events in ≥25% of patients receiving selpercatinib were edema, diarrhea, fatigue, dry mouth, hypertension, abdominal pain, constipation, rash, nausea, and headache.
"Selpercatinib had substantial antitumor activity in patients with RET fusion-positive lung cancers, including those who received selpercatinib as first-line therapy, those who had previously received at least platinum-based chemotherapy, and those with brain metastases," concluded Dr. Drilon and colleagues in their report. "The continued implementation of molecular screening strategies that include the ability to detect RET fusions will be critical for identifying patients with NSCLC who may benefit from selpercatinib."
The recommended dosage of selpercatinib is based on body weight; for those less than 50 kg, the recommended dosage is 120 mg twice daily, and for those greater than 50 kg, the recommended dosage is 160 mg twice daily.
For More Information
Drilon A, Oxnard GR, Tan DSW, et al (2020). Efficacy of selpercatinib in RET fusion–positive non–small-cell lung cancer. NEJM, 383:813-824. DOI:10.1056/NEJMoa2005653
Clinicaltrials.gov (2022). A study of selpercatinib (LOXO-292) in participants with advanced solid tumors, RET fusion-positive solid tumors, and medullary thyroid cancer (LIBRETTO-001). NLM identifier: NCT03157128.
Retevmo® (selpercatinib) prescribing information (2022). Eli Lilly and Company. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/213246s007lbl.pdf
US Food and Drug Administration (2022). FDA approves selpercatinib for locally advanced or metastatic RET fusion-positive non-small cell lung cancer. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-selpercatinib-locally-advanced-or-metastatic-ret-fusion-positive-non-small-cell-lung?utm_medium=email&utm_source=govdelivery
Image credit: Yale Rosen. Licensed under CC BY-SA 2.0
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