The FDA has granted accelerated approval to selpercatinib (Retevmo®, Eli Lilly and Company) for treatment of adult patients with locally advanced or metastatic rearranged during transfection (RET) gene fusion solid tumors that have progressed on prior systemic therapy, or who have no adequate alternative treatment options.
"Selpercatinib, a highly selective RET kinase inhibitor with central nervous system (CNS) activity, was developed specifically to treat patients with RET-altered cancers," wrote Vivek Subbiah, MD, an Associate Professor in the Investigational Cancer Therapeutics Department at MD Anderson Cancer Center, and colleagues, in their report of Libretto-001 (NCT03157128), on which approval was based. "Selpercatinib is active preclinically in several RET fusion-positive models of lung, thyroid, and other cancers."
Safety and efficacy were measured in the phase 1/2, open-label, multi-cohort, multicenter trial of selpercatinib. The accelerated approval is based on the outcomes of 41 patients with RET fusion–positive tumors that had disease progression, prior systemic therapy, or no adequate alternative treatment options; this did not include patients with non-small cell lung cancer and thyroid tumors. Treatment continued 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). Among the 41 patients being evaluated, median overall response rate was 44% and median duration of response was 24.5 months. The tumor types of which had responses include pancreatic adenocarcinoma, colorectal, salivary, unknown primary, breast, soft tissue sarcoma, bronchial carcinoid, ovarian, small intestine, and cholangiocarcinoma.
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.
"The data generated by this program thus far, in addition to the previously reported activity of selpercatinib in RET fusion-positive lung and thyroid cancers, provide clinical proof of concept that RET fusions are both central to oncogenesis and therapeutically actionable across diverse tumor lineages, thus positioning selpercatinib as a tumor-agnostic therapy," concluded Dr. Subbiah and colleagues in their report.
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
Subbiah V, Wolf J, Konda B, et al (2022). Tumour-agnostic efficacy and safety of selpercatinib in patients with RET fusion-positive solid tumours other than lung or thyroid tumours (LIBRETTO-001): a phase 1/2, open-label, basket trial. Lancet Oncol. DOI:10.1016/S1470-2045(22)00541-1
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.
US Food and Drug Administration (2022). FDA approves selpercatinib for locally advanced or metastatic RET fusion-positive solid tumors. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-selpercatinib-locally-advanced-or-metastatic-ret-fusion-positive-solid-tumors?utm_medium=email&utm_source=govdelivery
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