Dual costimulation blockade with the CD154-specific fusion protein dazodalibep and belatacept for prophylaxis of kidney allograft rejection.

Organ transplant immunosuppression includes daily calcineurin inhibitors and corticosteroids, which target broad, toxic metabolic pathways. This phase 2a, open-label, single-arm trial evaluated the efficacy and safety of combining dazodalibep (cluster of differentiation (CD)154-specific, also known as CD40 ligand-specific) with belatacept (CD80/86-specific) as the sole maintenance therapy in adults undergoing first, nonidentical kidney transplants from deceased or living donors. The primary endpoint was incidence of efficacy failure, defined as treated biopsy-proven acute rejection of grade 1A or higher, graft loss, or death at week 24. Secondary endpoints assessed efficacy components at weeks 12, 24, and 48 and safety. Among 23 patients treated with at least 1 dose, 13 (56.5%) completed the study. Twenty patients received a revised dosing regimen, and 5/20 (25%) experienced treated biopsy-proven acute rejection. No antibody-mediated rejection occurred. Kidney function was similar for patients who did and did not experience transplant rejection through 24 weeks. Most patients (96% [22/23]) experienced at least 1 treatment-emergent adverse event. No thrombotic events were observed. While the prespecified primary endpoint to prevent composite efficacy failure was not met among patients who completed this study, dazodalibep and belatacept dual biologic treatment was generally safe, well tolerated, and effective as the sole maintenance antirejection therapy.