Lilly announces positive registrational data for selpercatinib (LOXO-292) in heavily pretreated RET-altered thyroid cancers.

Eli Lilly and Company presented data from the LIBRETTO-001 clinical trial intended to support the registration of oral selpercatinib monotherapy , also known as LOXO-292, for the treatment of RET-altered thyroid cancers.

RET-altered thyroid cancers are comprised of two different populations, RET-mutant medullary thyroid cancer (MTC) and RET fusion-positive thyroid cancers. In the RET-mutant MTC registration dataset consisting of the first 55 enrolled patients with prior cabozantinib and/or vandetanib, selpercatinib treatment resulted in a 56 percent objective response rate (ORR) (95% CI: 42-70%). This population was heavily pretreated (53 percent previously treated with greater than 2 prior multikinase inhibitors), and ORR was similar regardless of prior multikinase inhibitor therapy. As of the data cut-off date of June 17, 2019, median duration of response (DOR) was not reached (95% CI: 11.1-NE) and median progression-free survival (PFS) was not reached (95% CI: 11.3-NE). Selpercatinib therapy also resulted in robust biochemical response rates (BRR) for serum tumor markers calcitonin (91% BRR) and carcinoembryonic antigen (64% BRR).

In a safety analysis of all 531 patients enrolled to LIBRETTO-001, selpercatinib was well-tolerated, with only nine patients (1.7%) discontinuing therapy due to treatment-related adverse events. The most commonly observed adverse events, regardless of attribution, were dry mouth, diarrhea, hypertension, increased liver enzymes, fatigue, constipation, and headache. These results were presented at the European Society for Medical Oncology (ESMO) Congress 2019 in Barcelona, Spain, in session LBA93, "Registrational Results of LOXO-292 in Patients with RET-Altered Thyroid Cancers", presented by Lori J. Wirth, M.D., medical director of head and neck cancers, Massachusetts General Hospital Cancer Center in Boston, Mass. Selpercatinib has received breakthrough therapy designation from the FDA.

"Current therapeutic options are often challenging for patients with first-line RET-altered thyroid cancers and are limited for patients who relapse. The data for selpercatinib show demonstrative efficacy and safety in both the first-line and relapsed settings. Patients with thyroid cancer have long sought targeted therapy tailored to the molecular nature of their disease, and we are hopeful that selpercatinib may be used as the standard of care in the future," said Wirth, who is lead investigator on the trial.

Selpercatinib Data in Cabozantinib/Vandetanib-Na�ve RET-Mutant MTC patients : Investigators also presented the results of selpercatinib in RET-mutant MTC patients who have received neither cabozantinib nor vandetanib. In this analysis of 76 patients, selpercatinib treatment resulted in a 59 percent ORR (95% CI: 47-70%). Median DOR and PFS were not reached in this treatment-na�ve population, as the vast majority of patients remain in response or progression-free.

Selpercatinib Data in Heavily Pretreated RET Fusion-Positive Thyroid Cancer Patients : Investigators also presented the results of selpercatinib in heavily pretreated RET fusion-positive thyroid cancer patients. In this analysis of 26 patients, selpercatinib treatment resulted in a 62 percent ORR (95% CI: 41-80%). Median DOR and PFS were not reached in this population, as the vast majority of patients remain in response or progression-free.

Trial Background : The LIBRETTO-001 Phase 1/II trial is the largest clinical trial of patients with RET-altered cancers treated with a RET inhibitor. The trial includes a dose escalation phase (Phase 1) and a dose expansion phase (Phase II). The Phase II portion of the trial had a primary endpoint of objective response rate (ORR) and secondary endpoints of DOR, PFS and safety. The primary analysis set for MTC regulatory submissions, as defined with the FDA, consists of the first 55 enrolled patients with RET-mutant medullary thyroid cancer who have experienced prior cabozantinib and/or vandetanib. All data presented at ESMO were as of a data cut-off date of June 17, 2019, and all efficacy measures utilized investigator assessments.