NEW YORK – Eli Lilly announced on Wednesday that its Phase III LIBRETTO-431 trial for the initial treatment of advanced or metastatic RET fusion-positive non-small cell lung cancer (NSCLC) is now openly enrolling patients. Enrollment will be capped at 400 participants.
The trial will examine the effects of selpercatinib (LOXO-292) in cancer patients who have had no prior treatment for their condition. Participants will be randomized to receive either selpercatinib or a cocktail of different chemotherapy drugs with or without pembrolizumab (Merck's Keytruda). RET fusions in patients will be identified through local testing.
RET fusions occur in 2 percent of NSCLC patients, and approximately 50 percent of RET-fusion tumors metastasize to the brain. Due to a lack of treatment options, the US Food and Drug Administration has granted breakthrough therapy designation to selpercatinib.
Selpercatinib is an orally administered drug in clinical development for cancers with abnormalities in the rearranged during transfection (RET) kinase. RET fusion cancers depend on this single activated kinase for their proliferation and survival. Selpercatinib is designed to block RET signaling as well as anticipated resistance mechanisms that cancer cells may acquire.
The primary endpoint for LIBRETTO-431 is to assess progression-free survival (PFS). Secondary endpoints include overall survival (OS), overall response rate (ORR), duration of response (DoR), and intracranial ORR.
Patients allocated to the control are allowed to crossover to the treatment arm at time of disease progression.
"This trial endeavors to generate outcome data that place patients with RET fusions alongside those with EGFR mutations and ALK fusions, as driver-positive populations that should be treated with targeted therapies in the first-line setting, rather than chemoimmunotherapy," Ben Solomon, principal investigator at the Peter MacCallum Cancer Centre in Melbourne Australia who worked on the preceding Phase I/II trial of selpercatinib, said in a statement.
In September, Lilly said it planned to file a new drug application with the FDA for selpercatinib by the end of 2019.