A phase 1 study of ABX196 in combination with nivolumab in patients with previously treated hepatocellular carcinoma (HCC)

429 Background: ABX196, a synthetically modified α-galactosylceramide (α-GalCer), activates invariant NKT (iNKT) cells and produced anti-tumor activity in Hepa 106 xenograft HCC models. Pre-administration of anti-PD1 antibodies prevented α-GalCer-induced iNKT cell anergy and may also enhance iNKT cell-induced T cell response. We report on a phase 1 study evaluating the combination of ABX196 plus nivolumab (N) in HCC patients previously treated with at least 1 line of prior systemic therapy. Methods: In a 3+3 dose escalation design, intramuscular ABX196 was dosed at 0.1, 0.2, or 0.4 µg 120 mins after N infusion on day 1 of every other 28-day cycle. N (240mg) was administered intravenously on day 1 and 15 of each cycle. Key objectives were to assess safety, MTD, and signs of clinical benefit. Study endpoints included incidence and severity of AEs, laboratory parameters, DLTs, ORR, and PFS. Results: 10 patients (8 males, 2 females) were enrolled: median age, 66y (49-76y); median # of prior systemic therapies, 2 (1-3), including 9 patients with prior immune checkpoint inhibitor (ICI) therapy; median # of ABX196 doses, 2.5 (1-8). There were 76 AEs (95% G1/G2) and 1 non-treatment related SAE. Common non-serious AEs included diarrhea (6), malaise/fatigue (6), AST/ALT increase (6), and only 1 injection site reaction. Maximum administered dose was 0.4 μg; MTD not reached. Clinical benefit was observed in 5 patients (50%) including 1 patient with a PR (ORR 10%) and 4 patients with SD (40%). Of these 5 patients, 3 had viral hepatitis. Median PFS for all patients was 113.5 days (49-450 days), but for those with clinical benefit it was 276 days (172-450 days). Conclusions: ABX196 plus N was very well tolerated without any DLTs or treatment emergent SAEs. In this small but heavily pre-treated HCC population, ABX196 plus N demonstrated promising signals of clinical benefit, including in patients with previous ICI therapy. These results support further clinical development of ABX196 in the front-line HCC setting. Clinical trial information: NCT03897543. [Table: see text]