Agenus announces publication of Phase 1b BOT+BAL data

Agenus (AGEN) announced the publication of Phase 1b data evaluating botensilimab, an Fc-enhanced anti-CTLA-4 antibody, in combination with balstilimab, an anti-PD-1 antibody, in patients with treatment-refractory hepatocellular carcinoma who had progressed following prior immunotherapy. The manuscript, titled “A phase 1b study of botensilimab and balstilimab in treatment-refractory hepatocellular carcinoma,” was published in Liver Cancer and is available at DOI: 10.1159/000551630. The publication reports results from an expansion cohort of the Phase 1b C-800-01 study in 19 patients with HCC who had progressed on or after prior immunotherapy. The cohort represents a difficult-to-treat population for which prospective data remain limited, including 47% of patients with albumin-bilirubin grade 2 liver function, a marker of poorer liver reserve and prognosis in HCC. In published HCC studies, ALBI grade 2 liver function has been linked to a 4- to 10-month decrement in median overall survival compared with ALBI grade 1, underscoring the poor prognosis and reduced responsiveness typically observed in this population.i Among 18 efficacy-evaluable patients, BOT+BAL demonstrated an objective response rate of 17%, including one complete response and two partial responses. The 18-week clinical benefit rate was 50%. Median duration of response was not reached, median progression-free survival was 4.4 months, and median overall survival was 12.3 months. All patients had received prior anti-PD-1 therapy, 68% had received prior tyrosine kinase inhibitors, and 58% had received prior atezolizumab/bevacizumab. One patient experienced stable disease for 66 weeks, supporting the conclusion that benefit with BOT+BAL was not confined to RECIST response alone. Treatment options after immune checkpoint inhibitor therapy in advanced HCC remain limited, and available systemic therapies have generally shown modest activity. Published studies evaluating lenvatinib, cabozantinib and regorafenib after ICI-based therapy have reported objective response rates of 6-14%, median progression-free survival of approximately 4-5 months and median overall survival of less than or equal to10.5 months.ii The BOT+BAL results therefore, provide early prospective evidence of activity in a post-ICI HCC population that included patients with adverse prognostic features often underrepresented in later-line studies.