Dr Wirth on the LIBRETTO-001 Trial of Selpercatinib in RET Fusion+ Thyroid Cancer

Lori Wirth, MD, associate professor, medicine, Harvard Medical School; medical director, Center for Head and Neck Cancers; Massachusetts General Hospital, discusses the phase 1/2 LIBRETTO-001 trial (NCT03157128) investigating selpercatinib (Retevmo) in adult and pediatric patients at least 2 years of age with advanced or metastatic RET fusion–positive thyroid cancer who require systemic therapy and who are radioactive iodine (RAI) refractory, if RAI is appropriate.

This conversation comes after the June 2024 FDA full approval of selpercatinib for this patient population. LIBRETTO-001 demonstrated that patients who received prior treatment (n = 41) achieved an overall response rate (ORR) of 85% (95% CI, 71%-94%), and those who were naive to systemic therapy (n = 24) experienced an ORR of 96% (95% CI, 79%-100%) when treated with selpercatinib.

LIBRETTO-001 was a first in-human trial that evaluated selpercatinib in patients with RET-driven cancers and included several different cohorts, Wirth begins. One cohort comprised patients with non–small cell lung cancer who had RET fusion–positive disease and had previously been treated with other therapies. Additionally, there were cohorts of patients with RET fusion–positive thyroid cancer who had received prior multi-kinase inhibitor therapy, she explains.

Moreover, the trial included a cohort of patients with RET fusion–positive medullary thyroid cancer who were treatment naive, Wirth continues. Patients with RET fusion–positive follicular-derived thyroid cancer were also enrolled, along with those with other RET-driven cancers, she elucidates, adding that the initial phase of the trial focused on dose finding, which was crucial for determining the optimal dosage of selpercatinib.

The primary end point at this stage was to assess the safety profile of selpercatinib and establish the recommended phase 2 dose, Wirth reports. Upon transitioning to the expansion phase, the study evaluated additional end points, such as ORR, duration of response, progression-free survival, and other important measures of clinical efficacy, she concludes.