Budigalimab, an anti-PD-1 inhibitor, for people living with HIV-1: a randomized, placebo-controlled phase 1b study

作者：Moti Ramgopal, Jacob Lalezari, Ana Gabriela Pires dos Santos, Preethi Krishnan, Tanaya R. Vaidya, Fei Zhou, Heide Betman, Patrick Dorr, Nael M. Mostafa, María L. Alcaide, Franco Felizarta, Jean‐Pierre Routy · 发表于：Nature Medicine · 年份：2025 · DOI：10.1038/s41591-025-03993-0 · 被引用次数：12 · 研究领域：HIV Research and Treatment、HIV/AIDS drug development and treatment、Immune Cell Function and Interaction

Abstract Chronic human immunodeficiency virus type 1 (HIV-1) disease results in immune exhaustion and dampened T cell responses, and programmed cell death 1 (PD-1) inhibitors offer a potential approach to enable viral control without antiretroviral therapy (ART) through reversal of these effects. Budigalimab is an investigational humanized anti–PD-1 monoclonal antibody. Multiple intravenous (IV) low doses of budigalimab (Stage 1: 2 mg n = 10, 10 mg n = 10, placebo n = 5, two doses every 4 weeks; Stage 2: 10 mg n = 11, placebo n = 5, four doses every 2 weeks (Q2W)) were assessed in people living with HIV (PLWH; n = 41) in a randomized, double-blind, multicenter, placebo-controlled phase 1 study with an analytical treatment interruption (ATI) to identify an efficacious regimen with a favorable safety profile in PLWH. The primary endpoints were safety, tolerability and pharmacokinetics. Demographics and baseline characteristics were balanced across treatment groups, except for sex, which was mostly male. All participants identified as cisgender. Budigalimab was well tolerated for up to 44 weeks, with 29 of 41 participants experiencing an adverse event (AE), including 2 participants who each experienced one grade 1 reversible immune-related AE (thyroiditis, hyperthyroidism). Three grade 3 AEs were reported by two participants and one serious AE by one participant; none were deemed related to treatment. IV budigalimab 10 mg Q2W resulted in a slight accumulation of drug in serum, w...