NCT07096609

Lenvatinib After Progression on Imatinib, Sunitinib, and Regorafenib for GIST Patients

A Single-center, Single-arm Phase II Study to Evaluate the Efficacy and Safety of Lenvatinib in Patients With Advanced Gastrointestinal Stromal Tumors (GIST) Who Have Failed Treatment With Imatinib, Sunitinib, and Regorafenib

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 48 (estimated)
• Sponsor: Asan Medical Center · Academic / Other
• Sex: All
• Age: 20 Years
• Healthy volunteers: Not accepted

Summary

The aim of this study is to evaluate the safety and efficacy of lenvatinib in patients with metastatic or advanced GIST who have failed at least imatinib, sunitinib, and regorafenib treatment.

Detailed description

The discovery of KIT gene mutations and the development of the KIT tyrosine kinase inhibitor imatinib (Glivec™, Novartis) have significantly improved the survival rates of patients with advanced and metastatic gastrointestinal stromal tumors (GIST). More recently, sunitinib (Sutene™, Pfizer) and regorafenib (Stivarga®, Bayer) have been proven effective as second- and third-line therapies, respectively, for patients who have failed imatinib treatment. However, nearly all patients eventually develop resistance to first-line imatinib, second-line sunitinib, and third-line regorafenib, resulting in disease progression. Although ripretinib, a fourth-line treatment, has demonstrated an improvement in progression-free survival to 6.3 months compared to placebo in the phase III INVICTUS trial, it remains inaccessible in many regions, including Korea, limiting its clinical application. Therefore, there is an urgent need for new therapeutic alternatives after imatinib, sunitinib, and regorafenib in clinical practice. Lenvatinib is a multi-targeted tyrosine kinase inhibitor with potent anti-angiogenic activity, primarily targeting VEGFR1-3 with IC₅₀ values of 4.7, 3.0, and 2.3 nmol/L, respectively. It also exhibits inhibitory activity against c-KIT (IC₅₀: 85 nmol/L) and PDGFR-α (IC₅₀: 29 nmol/L). Pharmacokinetically, lenvatinib is rapidly absorbed with a bioavailability of 85% and has an elimination half-life of approximately 28 hours. The LENVAGIST study, presented at ESMO 2024, was a phase II randomized, placebo-controlled trial that demonstrated the significant clinical activity of lenvatinib in patients with advanced GIST who had progressed after treatment with imatinib and sunitinib. In this study, the 4-month progression-free survival rate was 39% in the lenvatinib group versus 11% in the placebo group (HR 0.44; 95% CI 0.27-0.71; p=0.0008), and the median overall survival was 14.4 months versus 8.7 months, respectively. Treatment-related grade ≥3 adverse events were observed in 56.4% of patients in the lenvatinib group and 18.4% in the placebo group.

Conditions

• GIST

Interventions

Type	Name	Description
DRUG	Lenvatinib Capsules	Lenvatinib will be administered orally once daily at a dose of 12 mg (for patients weighing ≥ 60 kg) or 8 mg (for patients weighing \< 60 kg). Each treatment cycle consists of 4 weeks (i.e., 28 days).

Timeline

• Start date: 2025-10-29
• Primary completion: 2027-12-31
• Completion: 2027-12-31
• First posted: 2025-07-31
• Last updated: 2026-04-03

Locations

1 site across 1 country: South Korea