Background
Budigalimab and trosunilimab are recombinant IgG1 monoclonal antibodies that bind cell-surface expressed PD-1 receptor and α4β7 integrin, respectively. In people with HIV (PWH), it is hypothesized that the two may act synergistically to boost HIV-specific T-cell responses, leading to enhanced immuno-surveillance enabling ART-free viral control. This phase 2 study evaluated the safety and efficacy of budigalimab ± trosunilimab on viral control in PWH undergoing an analytical treatment interruption (ATI).
Methods
In this randomized, double-blind, placebo (PBO)-controlled, global trial, ART-suppressed PWH were randomized 1:1:1:2:2 to receive PBO, budigalimab 10mg Q2Wx4, trosunilimab 1600mg Q4Wx3, the combination of budigalimab 10mg + trosunilimab 800mg, or budigalimab 10mg + trosunilimab 1600mg. Study drugs were administered on the first day of the ATI and continued for 8 weeks. The primary study endpoint was plasma viral load (pVL)<1000 cp/mL at Week (Wk) 24 of ATI (Mantel-Haenszel chi-squared test for active arms vs PBO). Secondary endpoints were peak pVL before ART restart and time to viral rebound (pVL≥1000 cp/mL) during ATI.
Results
142/142 randomized PWH received ≥1 dose of study treatment. Demographics and baseline characteristics were similar across arms, with mean age 46.8 y and 85.9% male. All PWH experienced viral rebound ≥200 cp/mL during ATI, except 1 in PBO and 6 in the combination arms. At Wk 24, the proportion of PWH with pVL<1000 cp/mL was 23.8% with budigalimab 10mg + trosunilimab 800mg vs 5.0% in PBO (p=0.07) (Figure). No substantial differences were noted between arms for median peak pVL or median time to pVL≥1000 cp/mL. Across arms, 127/142 (89.4%) PWH experienced ≥1 AE, with 4 (2.8%) treatment-related serious AEs and 9 (6.3%) immune-related AEs (all in budigalimab arms), and no deaths. AEs were consistent with the known profiles of budigalimab and trosunilimab, with no new safety signals identified.
Conclusions
At Wk 24 of a large, global, phase 2 RCT, off-ART viral control was observed in nearly one quarter of PWH following low-dose finite-duration budigalimab 10mg + trosunilimab 800mg. Host-specific correlates of response require further study. While development of the combination has ended, these results support further study of immune-mediated therapies involving PD-1 blockade to achieve viral control without ART.
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