Patients with RET fusion–positive non–small cell lung cancer (NSCLC) comprise up to 2% of all NSCLC cases, but there are no targeted therapies currently approved for patients with this form of lung cancer. Selpercatinib (also known as LOXO-292) is an oral and highly selective investigational drug in clinical development for the treatment of patients with cancers that harbor abnormalities in the RET gene. Genomic alterations involving RET, which include fusions and activating point mutations, lead to overactive RET signaling and uncontrolled cell growth.
Selpercatinib was granted Breakthrough Therapy designation by the U.S. Food & Drug Administration in 2018 after initial data from LIBRETTO-001 trial showed it demonstrated antitumor activity in patients with RET fusion–positive non–small cell lung cancer (NSCLC), as well as strong evidence of durability.
Alexander Drilon, MD
At the International Association for the Study of Lung Cancer (IASLC) 2019 World Conference on Lung Cancer (WCLC), Alexander Drilon, MD, and colleagues reported data on a primary analysis set of 105 patients with RET fusion–positive NSCLC treated with selpercatinib (Abstract PL02.08). The LIBRETTO-001 trial includes 87 sites in 16 countries.
Results
Researchers presented data from the phase I/II trial, where they noted a high response rate in the primary analysis set of patients previously treated with platinum-based chemotherapy, with 68% achieving responses and a median duration of response of 20.3 months. The intracranial objective response rate was 91% (n = 10 of 11) for patients with target lesions in the brain at baseline.
“In this large cohort, selpercatinib’s response rate, durability, robust intracranial activity, and safety show promise."— Alexander Drilon, MD
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In the safety data set of all 531 patients enrolled to the study, five treatment-related adverse events occurred in ≥ 15% of patients: dry mouth, diarrhea, hypertension, increased AST, and increased ALT. Most adverse events were grade 1–2. Nine of 531 (1.7%) patients discontinued LOXO-292 due to treatment-related adverse events.
“In this large cohort, selpercatinib’s response rate, durability, robust intracranial activity, and safety show promise. Furthermore, this continues to confirm that RET fusions are clinically targetable alterations, placing them in the company of activating EGFR/ALK/ROS1 alterations. We are encouraged by this data, as there is currently an unmet need to provide genomically tailored therapy to patients with RET fusion–positive NSCLC,” concluded Dr. Drilon.
Disclosure: For full disclosures of the study authors, visit wclc2019.iaslc.org.
