US-based Eli Lilly and Company (Lilly) has started its LIBRETTO-431 clinical trial of LOXO-292 (selpercatinib), for treatment-naïve RET fusion-positive non-small cell lung cancer (NSCLC) patients.

The pharma firm will randomise the participants enrolled into the trial in 1:1 ratio to receive either selpercatinib or platinum-based (carboplatin or cisplatin) and pemetrexed therapy with or without pembrolizumab, as initial treatment of advanced or metastatic RET fusion-positive NSCLC.

Progression-free survival (PFS) is the primary endpoint and overall survival (OS), overall response rate (ORR), duration of response (DoR), and intracranial ORR include secondary endpoints of the study.

Peter MacCallum Cancer Centre principal investigator Ben Solomon said: “Given the remarkable results of the LIBRETTO-001 trial, I am excited to open this important Phase 3 trial of selpercatinib, a highly selective and potent molecule that has previously demonstrated sustained responses with a well-tolerated safety profile.

“This trial endeavours 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.”

Selpercatinib is used in treating cancers with abnormalities in RET kinase

According to the company, Genomic alterations in RET kinase, which include fusions and activating point mutations would result in overactive RET signalling and uncontrolled cell growth.

In addition, RET fusion cancers are primarily dependent on the single activated kinase for proliferation and survival and are highly susceptible to small molecule inhibitors targeting RET.

LOXO-292 is a highly selective and potent, oral investigational medicine, which is currently under clinical development for the treatment of cancers with abnormalities in the rearranged transfection (RET) kinase.

Lilly said that it has designed selpercatinib to inhibit native RET signalling along with anticipated acquired resistance mechanisms.

In addition, it has secured FDA breakthrough designation for Selpercatinib in RET fusion-positive NSCLC, RET-mutant medullary thyroid cancer (MTC) and RET fusion-positive thyroid cancers.