International, open-label phase 2 study of regorafenib plus pembrolizumab in patients with advanced hepatocellular carcinoma (HCC) previously treated with immune checkpoint inhibitors (ICI).

• DOI: 10.1200/jco.2024.42.16_suppl.4007
• Publication Date: 2024-06-17T14:16:54Z
• Authors: Anthony B. El-Kho...; Tae-You Kim; Jean-Frédéric Blanc; Olivier Rosmorduc; Thomas Decaens; Philippe Mathurin; Philippe Merle; Farshid Dayyani; Gianluca Masi; Tiziana Pressiani; Peter Robert Galle; Ken Hatogai; Yuko Ishii; Henrik Seidel; Udo Mueller; Stacey Anastasia ...; Mohamed Bouattour
• Keywords: Regorafenib; Lenvatinib; Immune checkpoint

4007 Background: The optimal second-line treatment for HCC after ICI is not established. Regorafenib approved of advanced sorafenib. primary aim this study was to evaluate the activity regorafenib plus pembrolizumab in patients with who progressed on only one prior regimen. Methods: Patients aged ≥18 years, CP Class A, BCLC stage B or C, and ECOG PS 0 1 received oral 90 mg once daily 3 weeks (wk) on/1 wk off i.v. 400 every 6 wk. dose could be escalated 120 first 4-wk cycle if tolerated. Pembrolizumab reductions were allowed. Cohorts defined by treatment: Cohort = atezolizumab + bevacizumab; 2 any other regimen (alone combination). Primary endpoint overall response rate (ORR) independent central review (RECIST 1.1). Results: 95 treated 8 countries; appeared have more favorable disease characteristics (Table). Most common ICIs durvalumab (30%), nivolumab ipilimumab (22%), (19%). Overall, median follow up 7.1 months (mo). Median duration regorafenib/pembrolizumab (including interruptions, delays) shorter vs (11.0/9.4 21.4/24.1 wk). ORR 5.9% 11.1% 2; stable rates 48.5% 63.0%, respectively. PFS 2.8 mo 4.2 2. treatment-emergent adverse events (TEAE) grade 56% 4 5%; drug-related TEAE occurred 37% 3%, One patient (Cohort 1) had a 5 (cardiac arrest). palmar-plantar erythrodysesthesia syndrome (39%), asthenia (33%), decreased appetite (32%), diarrhea (28%), hypertension (20%). Biomarkers assessed paired biopsies (baseline 6/day showed on-treatment macrophages angiogenesis RNA signatures. Conclusions: To our knowledge, prospective evaluation kinase inhibitor an following first-line therapy HCC. modest second line regimens. safety profile combination consistent those either drug. Optimal progress remains unmet need. Biomarker findings will detailed presentation. Clinical trial information: NCT04696055 . [Table: see text]