Durable efficacy of selpercatinib in patients with RET fusion+ solid tumors, with a focus on GI tumors: LIBRETTO-001.

Abstract

746 Background: Selpercatinib, a first-in-class highly selective and potent RET kinase inhibitor with CNS activity, is approved in multiple countries for the treatment of RET-activated cancers. This update includes more patients (pts, n=52) and 16 months (mo) longer follow-up (data cut-off: 13Jan2023) in RET fusion+ solid tumors other than lung/thyroid with a focus on GI histologies. Methods: The phase 1/2 LIBRETTO-001 trial (NCT03157128) enrolled pts with locally advanced/metastatic RET fusion+ solid tumors. 51/52 pts received the recommended dose of 160 mg orally. The efficacy analysis set consisted of pts enrolled ≥6 months prior to the cut-off date. Primary endpoint was objective response rate (ORR) by independent review committee (IRC). Secondary endpoints included ORR by investigator (INV), duration of response (DoR), progression-free survival (PFS), and safety. Results: Of the 52 pts with RET-activated solid tumors other than lung or thyroid, 51.9% were female with a median age of 54.0 years. The majority (31/52) of patients had GI RET fusion+ tumor types, with pancreatic (N=13) and colorectal (N=13) as the most common (Table). 47 pts received prior systemic therapy (median prior lines: 2, range 0-9); 28.8% received ≥3 lines. In 52 efficacy-evaluable pts, confirmed ORR by IRC was 44.2% (23/52, 95% CI: 30.5, 58.7). ORR by IRC for pts with pancreatic tumors was 53.8% and for colorectal tumors was 30.8%. Clinical benefit (complete response + partial response + stable disease ≥16 weeks) was observed in 67.3% (35/52) of pts. Median DoR was 37.2 mo (95% CI: 13.3, NE) for overall pts (Table). No new safety signals were identified compared to previous reports. 4 grade 5 AEs were observed (unrelated to treatment by INV), and 2 pts discontinued due to treatment-related AEs per INV. Conclusions: Selpercatinib continued to demonstrate durable antitumor activity and tolerable safety in pts with RET fusion+ cancers across multiple tumor types and fusion partners, including difficult-to-treat GI cancers with poor results in standard-of-care options, such as pancreatic and colorectal. These results emphasize the importance of comprehensive genomic profiling across all tumor types in order to identify actionable oncogenic drivers, including RET fusions. Clinical trial information: NCT03157128 .[Table: see text]