Phase 2 study of cabozantinib (Cabo) combined with ipilimumab (Ipi)/nivolumab (Nivo) and transarterial chemoembolization (TACE) in patients with liver limited unresectable hepatocellular carcinoma (uHCC).

543 Background: The purpose of this study is to test the safety and efficacy of a multimodality approach in liver limited uHCC including patients (pts) with high risk features such as diffuse infiltrative bilobar disease with prior Locoregional Treatment (LRT), portal vein branch thrombus (PVT), or liver dysfunction. Methods: Single arm, two-institution, open label Phase 2 study. Pts with liver limited uHCC, no prior systemic treatment and Child-Pugh A-B7 were eligible. Prior LRT was allowed if completed >3mo prior to enrollment. Treatment regimen: Ipi 1mg/kg + Nivo 3mg/kg i.v. x 1 dose, followed by TACE. Post-TACE, Nivo 480mg i.v. + Cabo 40mg p.o. days 1-28, given every 28 days for up to 24mon. Primary endpoints are complete response (CR) rate (mRECIST) and progression-free survival rate at 6mo (PFS-6). Results: To date, 24 pts have been treated (see Table for patient characteristics), including 5 pts with PVT. Interim analysis presented here occurred after clearance of pre-specified futility and safety analysis. All patients completed the planned TACE. Median PFS, mOS and PFS-6 are 6.3mo, 13.0mo, and 55%. Best response for evaluable pts (n=18) is shown in Table. Overall response and disease control rate were 61% and 89%. Five of 18 evaluable pts had a complete response (CR; 28%), overall response was 11/18 (61%). Two pts with PR and CR on protocol (baseline tumor size 13.2cm and 14cm) underwent hepatectomy after 7.6mo and 4.6mo on protocol. Both remain alive and in remission after 38.8 and 39.3mo (tumor necrosis at resection 80% and 100%). The most common treatment related adverse events (TRAE) all grade (G) were Hand-Foot-Syndrome (29%), Hypothyroidism (25%), and Diarrhea/Pruritus/AST elevation (each 17%). G 3/4 TRAE occurred in 9pts (38%). No G5 TRAE were reported. Conclusions: Induction Ipi/Nivo followed by TACE and consolidation with cabo+nivo appears to be a feasible treatment approach for liver limited uHCC with a manageable safety profile and encouraging anti-tumor activity. We observed long-term remissions in pts converted to resectable on protocol. Updated data will be presented at the meeting. Clinical trial information: 04472767 . Number % Age (median) 67y (range 50-87) --- Gender Male Female 204 8317 Race/Ethnicity Asian Non-Hispanic White Hispanic Other 14541 5821174 Etiology Hepatitis B Hepatitis C Other 8610 332542 Child-Pugh Score A5/6 B7 213 8812 Prior LRT Yes No 1410 5842 Best Response (mRECIST; n=18) CR PR SD PD 5652 28332811