Lilly Presents Updated Data on Retevmo® (selpercatinib) in Advanced RET Fusion-Positive Non-Small-Cell Lung Cancer (NSCLC)
Eli Lilly and Company announced updated data from the Phase 1/2 LIBRETTO-001 trial of Retevmo® (selpercatinib 40 mg & 80 mg capsules) in patients with RET fusion-positive non-small cell lung cancer (NSCLC). Retevmo (marketed as Retsevmo® outside of the U.S.) is a selective and potent RET kinase inhibitor that is approved in multiple countries including the United States for treatment of adult patients with metastatic rearranged during transfection (RET) fusion-positive NSCLC, and the treatment of adult and pediatric patients 12 years of age and older with advanced or metastatic RET-mutant medullary thyroid cancer (MTC) who require systemic therapy, or advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate). These data were presented at the European Lung Cancer (ELCC) 2022 (poster 27p).
The updated analysis utilized a June 15, 2021, data cut-off and included 355 patients who were eligible for efficacy analysis, 247 of which were previously treated with at least one line of platinum chemotherapy and 69 of which were treatment-naïve. Patients who were previously treated with at least one line of platinum chemotherapy received a median of two prior treatment regimens (range: 1-15), with 58% having received anti-PD-1 or anti-PD-L1 therapy. Responses are based on an independent review committee (IRC) assessment.
Among 247 patients previously treated with platinum chemotherapy, the confirmed objective response rate (ORR) was 61.1% (95% CI: 54.7-67.2%) and among 69 treatment-naïve patients, the confirmed ORR was 84.1% (95% CI: 73.3-91.8%). Twenty-six patients had measurable central nervous system (CNS) metastases at baseline and treatment with Retevmo resulted in a CNS ORR of 84.6%, with 22 patients having a confirmed best response of complete response or partial response.
At a median follow-up of approximately two years in both the treatment-naïve and platinum-chemotherapy pretreated populations, median duration of response (DoR) is estimated at 20.2 (55.2% censoring rate; 20.3 months median duration of follow-up) and 28.6 (60.9% censoring rate; 21.2 months median duration of follow-up) months, respectively and median progression free survival (PFS) is estimated at 22.0 (53.6% censoring rate; 21.9 months median duration of follow-up) and 24.9 (55.9% censoring rate; 24.7 months median duration of follow-up) months, respectively. Of the 26 patients with measurable CNS disease, Retevmo treatment resulted in a median intracranial PFS of 19.4 months. These median estimates remain immature.
Safety among patients in this cohort was consistent with the known safety profile of Retevmo. In the safety population (all NSCLC patients that received at least one dose of Retevmo, N=356), the most common adverse events (AEs in ≥25% of patients) were dry mouth, diarrhea, hypertension, increased ALT/AST, peripheral edema, constipation, rash, headache, and fatigue. Thirty-four patients discontinued due to an adverse event (10%), eleven (3%) of which were deemed related to Retevmo.
A global, randomized, Phase 3 trial is currently recruiting and will compare treatment with Retevmo to the current standard of care in the first-line treatment of advanced or metastatic RET fusion-positive NSCLC.
Retevmo was the first RET inhibitor to receive Accelerated Approval from the U.S. Food and Drug Administration (FDA) in May 2020 and was first approved by the European Commission in February 2021. Retevmo was approved under the FDA's Accelerated Approval regulations based on the LIBRETTO-001 Phase 1/2 trial's endpoints of objective response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.