955P IMMUNIB trial (AIO-HEP-0218/ass): A single-arm phase II study evaluating safety and efficacy of immunotherapy with nivolumab in combination with lenvatinib in advanced hepatocellular carcinoma

The field of systemic therapy in hepatocellular carcinoma (HCC) has significantly evolved over the last years, and IO-based combinations therapies are the current standard of care. Nivolumab is a recombinant human IgG4 mAb targeting PD-1 with clinically meaningful activity in about 15-20% of HCC patients. Combinations of anti- angiogenic multikinase inhibitors, including lenvatinib, and PD-1/PD-L1 inhibitors have demonstrated remarkable antitumor activity with manageable toxicity in several tumor types, including HCC. The IMMUNIB trial aimed to evaluate the efficacy of nivolumab in combination with lenvatinib as first line treatment in patients with advanced HCC. This investigator-initiated single-armed phase II trial (NCT03841201) recruited 50 patients (pts) at 8 sites in Germany between 06/2019 and 05/2021. Primary efficacy endpoint was objective response rate (ORR) according to investigator assessed RECIST 1.1. Secondary endpoints included time to progression (TTP), progression free survival (PFS), overall survival (OS) and safety. Out of 50 enrolled pts (24 BCLC B, 18 BCLC C, 7 not evaluable) 49 received at least one dose of the combination treatment. The ORR by RECIST 1.1 was 32% (CR 6%, PR 26%, SD 42%, PD 12%). Median PFS was 9.0 mo. Median TTP was 9.89 mo (0.7 at 6 mo, 0.43 at 12 mo, 0.31 at 18 mo) and median OS was 25.36 mo (24 events). Of note, at EOS 26 pats were still alive, of whom 13 pats were without progression. 47 (96%) pts experienced at least one TRAE, of which 29 pts (59%) encountered at least one TRAE ≥ grade 3. 16 (32.7%) pts had at least one SAE related to the study medication, whereof 14 pts (29%) experienced at least one treatment related SAE ≥ grade 3. No new safety signals were observed for the combination of nivolumab and lenvatinib. Although the study failed to reach its prespecified ORR of at least 43%, the high activity in all efficacy endpoints with a mOS of more than 25 mo supports the further investigation of the combination in HCC.