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Eli Lilly's Selpercatinib Shows Strong Activity in RET Fusion-Positive NSCLC

NEW YORK – In the Phase I/II LIBRETTO-001 study, 68 percent of 105 heavily pretreated non-small cell lung cancer patients with RET fusions saw their tumors shrink after treatment with Eli Lilly's investigational RET inhibitor selpercatinib, researchers reported today at the World Conference on Lung Cancer.

Lilly, which acquired selpercatinib, or LOXO-292, with the purchase of Loxo Oncology earlier this year, also issued a statement on the results of the study, highlighting that the drug demonstrated impressive activity against NSCLC that has spread to the brain. Approximately 50 percent of RET-fusion tumors metastasize to the brain, and in this subset of patients in the trial, selpercatinib had an objective response rate of 91 percent. 

In order to participate in this study, NSCLC patients had to have progressed following platinum-based chemotherapy and on certain immunotherapies. Median duration of response in the trial was around 20 months, and median progression-free survival was 18.4 months. As of the June 17 data cut off, most patients in the study were still responding to selpercatinib or were progression free.

RET fusions occur in 2 percent of NSCLC patients, who lack treatment options, and the US Food and Drug Administration has granted breakthrough therapy designation to selpercatinib. Lilly hopes to submit data from this study as part of its new drug application with the FDA for selpercatinib later this year.

"In two and half years, Loxo Oncology advanced this molecule from first human dose to submission ready data, demonstrating the power of precision oncology to rapidly translate scientific discovery into treatments for patients," said Lilly Oncology President Anne White.

Selpercatinib was well tolerated among all 531 patients in LIBRETTO-001 with RET fusion-positive cancers. Nine patients discontinued treatment due to toxicities. Patients commonly experienced dry mouth, diarrhea, hypertension, and increased liver enzymes.

"This [data] continues to confirm that RET fusions are clinically targetable alterations, placing them in the company of activating EGFR/ALK/ROS1 alterations," Alexander Drilon, an oncologist at Memorial Sloan Kettering who is lead investigator of the trial, said in the Lilly statement.

At the same meeting, researchers also presented data on the drug's safety and efficacy when given to 34 RET fusion-positive NSCLC patients who were treatment naïve. In this subset, 85 percent saw their tumors shrink, and median duration of response and progression-free survival haven't been reached.

Lilly is also studying selpercatinib in patients with RET-mutant medullary thyroid cancer and advanced RET fusion-positive thyroid cancer who have progressed on other treatments and lack options.

In a separate announcement today, Thermo Fisher Scientific said it had signed an agreement with Lilly to develop a companion diagnostic to identify both NSCLC and thyroid cancer patients with RET alterations who might benefit from selpercatinib. After clinical validation of the Oncomine Dx Target test for this purpose, Thermo Fisher will submit a supplemental premarket approval application with the FDA to broaden the test's indication.