Phase 3 Study of Selpercatinib Meets Primary PFS End Point in NSCLC
Patients with RET fusion-positive advanced or metastatic non–small cell lung cancer had a survival benefit when treated with selpercatinib in the LIBRETTO-431 study.
Topline results from the LIBRETTO-431 trial of selpercatinib in RET fusion-positive advanced or metastatic NSCLC build on data from LIBRETTO-001: © SciePro -www.stock.adobe.com
Selpercatinib (Retevmo) given as an initial treatment for patients with RET fusion-positive advanced or metastatic non–small cell lung cancer (NSCLC) demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) vs platinum-based chemotherapy plus pemetrexed with or without pembrolizumab (Keytruda), meeting the primary end point of the LIBRETTO-431 study (NCT04194944).1
Topline results from the LIBRETTO-431 study were based on a pre-specified interim efficacy analysis conducted by an independent data monitoring committee. For safety, adverse events (AEs) with selpercatinib were generally consistent with those identified across the previous studies. These data build on findings from LIBRETTO-001 (NCT03157128), in which clinically meaningful and durable responses were observed with selpercatinib across a variety of tumor types in patients with RET-driven cancers.
The full results from LIBRETTO-431 will be presented at an upcoming medical meeting, submitted to a peer-reviewed journal, and discussed with health authorities.
"The LIBRETTO-431 trial aims to answer an important question about the selection of initial treatment for people with advanced RET fusion-positive NSCLC and these results suggest [selpercatinib] should be considered a first-line standard of care," said David Hyman, MD, chief medical officer, Eli Lilly and Company, in the press release.
Selpercatinib is a highly selective and potent RET kinase inhibitor with central nervous system (CNS) activity. Previously in September 2022,the FDA approved selpercatinib as an oral prescription medicine at doses of 120 mg or 160 mg dependent on weight (<50 kg or ≥50 kg, respectively), and taken twice daily until disease progression or unacceptable toxicity for adult patients with RET fusion-positive advanced or metastatic solid tumors.
Now, the randomized, open-label, phase 3 LIBRETTO-431 is assessing selpercatinib compared with platinum-based chemotherapy of either cisplatin or carboplatin plus pemetrexed with or without pembrolizumab. This is the first randomized trial to compare the safety and efficacy of a targeted therapy to a PD-1 inhibitor plus chemotherapy in a biomarker-selected patient population.
Patients aged 18 years and older with histologically or cytologically confirmed, Stage IIIB-IIIC or Stage IV non-squamous NSCLC that is not suitable for radical surgery or radiation therapy, and those who have A RET gene fusion will be eligible for enrollment in the study.2 Patients also must have an ECOG performance status of 0-2, adequate hematologic, hepatic, and renal function, and the ability to swallow capsules. Men and women of reproductive potential must also agree to use birth control for the duration of treatment and for 6 months after.
The primary end point is PFS with secondary end points of disease control rate, PFS2, overall response rate (ORR), duration of response (DOR), overall survival, intracranial ORR, intracranial DOR, time to deterioration of pulmonary symptoms, and time to CNS progression.
With an estimated enrollment of 250 patients, the study plans to be completed in July 2027.
"Additionally, this clinically meaningful achievement of improved outcomes underscores the importance of timely and comprehensive genomic testing to inform initial treatment decisions for all patients with NSCLC. The results of this study provide further confirmation that RET status – like EGFR, ALK, and others in the family of lung cancer oncogenic drivers – should be known prior to initiating therapy. We look forward to sharing these data in more detail with the oncology community," said Hyman, in the press release.1
