Background
Budigalimab and trosunilimab, recombinant IgG1 monoclonal antibodies that bind cell-surface PD-1 receptor and α4β7 integrin, respectively, are being studied as a potential strategy for immune-mediated control of HIV. In oncology indications, higher doses of budigalimab (250-500mg) are associated with immune-related adverse events (irAEs) in ~40% of patients (5% Grade [Gr]≥3). However, the safety profile of budigalimab at low dose (10mg) and finite duration in people with HIV (PWH) is unknown. Here we report preliminary findings of irAEs in PWH receiving low-dose budigalimab ± trosunilimab as part of a randomized, placebo (PBO)-controlled, global phase 2 trial including an analytical treatment interruption (ATI).
Methods
PWH on stable ART were randomized to budigalimab 10mg IV or PBO on Day 1, and Week (Wk) 2, 4, 6 and trosunilimab 800mg or 1600mg IV or PBO on Day 1 and Wk 4, 8. All PWH stopped ART on Day 1 and continued a closely monitored ATI until ART restart criteria were met (or until study end). Diagnosis of irAE was based on investigator’s judgment, taking into account clinical findings, complementary tests, and specialist evaluation, as needed.
Results
All (142/142) randomized PWH received at least one dose of study treatment. Baseline characteristics included mean age 46.8 y, 85.9% male, 19.0% Black/African American and 72.5% White, mean CD4+ T-cell count 848 cells/μL, and mean duration on ART 13.4 years. At Wk 24 analysis, 9/121 (7.4%) PWH receiving active treatment experienced an irAE (Gr 1: 5/9; Gr 2: 1/9; Gr 3: 3/9) (Table). Most were nonserious and reversible, and all were in budigalimab-containing arms. Thyroid-related irAEs were the most common. One PWH receiving budigalimab + trosunilimab experienced new onset of non-reversible diabetes mellitus (DM), serious (with reversible diabetic ketoacidosis) that was deemed related to budigalimab, with classic presentation of an anti-PD-1 irAE.
Conclusions
Among PWH treated with low-dose, finite-duration budigalimab ± trosunilimab, the frequency of irAEs (7%), including Gr≥3 events (2%), was low compared with oncology populations (~40%) treated with higher budigalimab doses. One case of anti-PD-1-mediated new-onset DM was reported in a participant receiving budigalimab + trosunilimab and was not reversible.
Table or Figure
