HCC has a mortality/morbidity ratio of 0.98 and a five-year survival rate of only about 5%-6%, indicating a very poor prognosis. Nivolumab is a programmed death receptor-1 (PD-1) inhibitor. H101, an E1B gene deleted oncolytic adenovirus, is known to have significant antitumor activity. In addition, local injection of H101 might enhance the effect of antitumor therapies (chemotherapy and radiotherapy). We report on the safety and efficacy of H101 in combination with nivolumab in patients (pts) with advanced HCC.
This single-arm, phase II study enrolled pts with HCC who failed prior systemic therapy. The combined treatment period starts from day 8, which will be recorded as the first cycle. Eligible pts received i.v. H101 (2 vials, on day 8) and i.v. nivolumab (3mg/kg, on day 9) followed by every 2 weeks. While H101 could be injected once every 4 weeks or suspended, depending on the percentage of CD8+ lymphocytes. Treatment continued until disease progression, unacceptable toxicity, consent withdrawal, or the physician’s decision. . The primary endpoint was objective response rate (ORR) per RECIST v1.1. and 6-month OS% was the other co-primary endpoint. The secondary endpoints included progression-free survival (PFS), overall survival (OS), disease control rate (DCR), duration of response (DOR), safety and exploratory bioinformatics analysis.
Up to Mar 2022, 21 pts were enrolled in cohorts. Of 18 evaluable pts, confirmed ORR and DCR were 11.1% and 38.9% respectively, with 2 partial responses (PR) and 5 stable diseases (SD), and 6-month OS% was 77.8%. Median PFS was 2.27 months [95% confidence interval (CI), 1.44-3.09], median OS was 15.04 months [95% CI, 8.33-21.76] and median DOR was 6.51 months. The most common treatment-emergent adverse events (TEAEs) in all pts were low-grade fever (90%) and pain related to centesis (60%). No grade 4/5 adverse events were reported.
H101 in combination with nivolumab showed promising activity with well-tolerated toxicities in pts with advanced HCC. Updated results will be presented.
MIT-003 Institutional)/CA209-7CE (BMS).
Z. Meng.
Bristol Myers Squibb.
All authors have declared no conflicts of interest.