Sequential or up-front triple combination with durvalumab, tremelimumab, and bevacizumab for patients with unresectable hepatocellular carcinoma (AIO-MONTBLANC): Safety interim analysis.

4122 Background: The combination of immune checkpoint inhibitors (ICI) durvalumab (durva) and tremelimumab (treme) has been approved for first-line (1L) therapy for advanced hepatocellular carcinoma (aHCC) and represents an alternative to combined atezolizumab and bevacizumab (bev). The MONTBLANC trial evaluates the efficacy and safety of combined durva, treme and bev in patients (pts) with aHCC (NCT05844046). Methods: This investigator-initiated, international, randomized phase 2 trial is the first to investigate the combination of durva, treme and bev. 70 pts with aHCC not amenable to curative treatment or locoregional therapy and preserved (Child-Pugh A) liver function are randomized in a 1:1 ratio to an early escalation arm (A) or triple treatment arm (B). Pts in arm A initially receive durva+treme with the addition of bev upon detection of disease progression or failure to achieving objective radiological response. Pts in arm B receive upfront durva, treme and bev. Durva, treme and bev are given in standard doses. The primary endpoint is overall response rate. Secondary endpoints include overall survival, progression-free survival and safety. We present the data of the second planned safety interim analysis. Results: 25 pts (arm A: 14, arm B: 11) were included in this analysis (04/2023 – 08/2024). Patients in arm A had a lower proportion of ECOG 0 (A: 78.6% vs B: 90.9%), higher proportion of Child Pugh A6 (A: 21.4% vs B: 9.1%), BCLC C (A: 78.6% vs B: 63.6%), macrovascular invasion (A: 42.9% vs B: 36.4%) and AFP ≥400 ng/mL (A: 42.9% vs B: 18.2%). Most adverse events (AE) were grade (G) 1 or 2. In arm A, there were 17 G3 AE, 1 G4 AE and 4 G5 AE. In arm B, 4 G3 AE and 1 G5 AE occurred. 18 serious AE (SAE) occurred in arm A and 2 SAE in arm B. There was one treatment-related death in arm A (ICI hepatitis) and none in arm B. In the first 6 months on treatment, there were no significant changes in ALBI score, Child Pugh score or ECOG performance status in both arms. Conclusions: This planned safety interim analysis did not reveal signals of unmanageable toxicity or deteriorating liver function through the addition of bev to durva/treme in the 1L treatment of pts with aHCC. Clinical trial information: NCT05844046 .