Open-label, randomized phase 2 trial (OCTOPUS-1) evaluating whether adding low-dose nivolumab (0.3 mg/kg; 1 or 3 doses) to JNJ-73763989 (siRNA) plus nucleos(t)ide analog (NA) improved HBsAg seroclearance in HBeAg-negative, virologically suppressed chronic hepatitis B (CHB) adults over a 24-week treatment period with 48-week follow-up.
No participant achieved the primary endpoint of HBsAg seroclearance at follow-up week 24; only 1/37 (Arm 2) achieved seroclearance at follow-up week 48. Both arms showed robust HBsAg declines at week 24 (Arm 1: −2.01 log10 IU/mL; Arm 2: −2.10 log10 IU/mL), but a cross-study comparison with REEF-1 showed no added benefit from the loading dose or nivolumab.
- Very small sample (n=37), limiting power to detect differences between arms. - Open-label design without a placebo-controlled arm within the same trial. - No clear mechanistic link found between HBV-specific T-cell activity and HBsAg response, leaving the basis for PD-1 augmentation uncertain.
Adding low-dose nivolumab to JNJ-3989 + NA did not meaningfully improve HBsAg seroclearance rates in virologically suppressed, HBeAg-negative CHB patients, though the combination appeared safe. Clinicians should not expect checkpoint inhibitor augmentation at this dose to close the gap to functional cure in this population.
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