Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · 2026
No Impact of Low-Dose Nivolumab Addition to JNJ-73763989 on Hepatitis B Surface Antigen Declines in Chronic Hepatitis B: The OCTOPUS-1 Study.
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Asselah Tarik, Fung Scott K, Akhan Sila, Chuang Wan-Long, Buti Maria, Brunetto Maurizia, Agarwal Kosh, Diba Camellia, Jezorwski John, Berger Véronique, T'jollyn Huybrecht, Tsou Wen-I, Kakuda Thomas N, Lonjon-Domanec Isabelle, Nalpas Catherine, Guinard-Azadian Carine, Verbinnen Thierry, Lathouwers Erkki, De Creus An, Lenz Oliver, Biermer Michael
Аннотация
BACKGROUND & AIMS: JNJ-73763989-based treatments (evaluations ongoing) reduce hepatitis B surface antigen in patients with chronic hepatitis B, but hepatitis B surface antigen seroclearance is rare. OCTOPUS-1, an open-label, randomized phase II study, assessed the efficacy and safety of adding low-dose nivolumab (programmed death 1 inhibitor) to JNJ-73763989 + nucleos(t)ide analog.
METHODS: Hepatitis B surface antigen-negative, virologically suppressed participants with chronic hepatitis B received JNJ-73763989 loading dose (200 mg once weekly) for 4 weeks then every 4 weeks until week 24 with daily nucleos(t)ide analog. Nivolumab (0.3 mg/kg) was administered at week 16 for arm 1 and at weeks 16, 20, and 24 for arm 2; both arms had 48-week follow-ups.
RESULTS: Thirty-seven participants were enrolled (arm 1, 18; arm 2, 19); all completed the study. None achieved the primary endpoint of hepatitis B surface antigen seroclearance at 24-week follow-up, but 1 (arm 2) achieved hepatitis B surface antigen seroclearance at 48-week follow-up. Both arms had robust mean [standard error] hepatitis B surface antigen changes from baseline before nivolumab administration (arm 1, -1.32 [0.12]; arm 2, -1.41 [0.16] log10IU/mL), at week 24 (arm 1, -2.01 [0.09]; arm 2, -2.10 [0.13] log10IU/mL), and at 48-week follow-up (arm 1, -1.23 [0.13]; arm 2, -1.54 [0.21] log10IU/mL). The mean receptor occupancy (determined 2 hours postinfusion at week 16) was ≥70% and ≥90% in arms 1 and 2 with no clear association between hepatitis B virus-specific T-cells and hepatitis B surface antigen. No serious adverse events, grade 3/4 adverse events, or adverse events leading to discontinuation were reported; 2 participants experienced asymptomatic transient hyperthyroidism. Cross-study analysis with REEF-1 (virologically suppressed, hepatitis B e-antigen-negative participants) revealed no additional benefit of loading dose or nivolumab.
CONCLUSIONS: JNJ-73763989 + nucleos(t)ide analog + nivolumab treatment was generally safe and led to robust hepatitis B surface antigen declines; no hepatitis B surface antigen seroclearance was observed.
CLINICALTRIALS: gov, Number: NCT05275023.
METHODS: Hepatitis B surface antigen-negative, virologically suppressed participants with chronic hepatitis B received JNJ-73763989 loading dose (200 mg once weekly) for 4 weeks then every 4 weeks until week 24 with daily nucleos(t)ide analog. Nivolumab (0.3 mg/kg) was administered at week 16 for arm 1 and at weeks 16, 20, and 24 for arm 2; both arms had 48-week follow-ups.
RESULTS: Thirty-seven participants were enrolled (arm 1, 18; arm 2, 19); all completed the study. None achieved the primary endpoint of hepatitis B surface antigen seroclearance at 24-week follow-up, but 1 (arm 2) achieved hepatitis B surface antigen seroclearance at 48-week follow-up. Both arms had robust mean [standard error] hepatitis B surface antigen changes from baseline before nivolumab administration (arm 1, -1.32 [0.12]; arm 2, -1.41 [0.16] log10IU/mL), at week 24 (arm 1, -2.01 [0.09]; arm 2, -2.10 [0.13] log10IU/mL), and at 48-week follow-up (arm 1, -1.23 [0.13]; arm 2, -1.54 [0.21] log10IU/mL). The mean receptor occupancy (determined 2 hours postinfusion at week 16) was ≥70% and ≥90% in arms 1 and 2 with no clear association between hepatitis B virus-specific T-cells and hepatitis B surface antigen. No serious adverse events, grade 3/4 adverse events, or adverse events leading to discontinuation were reported; 2 participants experienced asymptomatic transient hyperthyroidism. Cross-study analysis with REEF-1 (virologically suppressed, hepatitis B e-antigen-negative participants) revealed no additional benefit of loading dose or nivolumab.
CONCLUSIONS: JNJ-73763989 + nucleos(t)ide analog + nivolumab treatment was generally safe and led to robust hepatitis B surface antigen declines; no hepatitis B surface antigen seroclearance was observed.
CLINICALTRIALS: gov, Number: NCT05275023.