Phase 2 ADD-IT1 tests propranolol, desloratadine, nutrient repletion, and morning immunotherapy in melanoma and liver cancer

This randomized University of Southern California study evaluates a bundled adjunct strategy for patients starting first-line PD-1/PD-L1-based therapy for advanced melanoma or hepatocellular carcinoma. The experimental group receives immunotherapy before noon together with propranolol, a nonselective beta-adrenergic blocker, desloratadine, a histamine H1 antagonist, and protocol-directed magnesium and vitamin D repletion when levels are low. The control receives the clinically appropriate immunotherapy regimen with routine infusion timing and supportive care.

The primary emphasis is on immune and inflammatory biomarkers over approximately 12 weeks, including cytokines and T-cell measures, with clinical activity explored rather than established by those biomarkers. The trial is not designed to isolate the contribution of morning dosing, either drug, or supplementation separately because they are combined in one intervention. The scientific rationale combines stress signaling, histamine signaling, nutrient repletion, and circadian timing as potential modifiers of checkpoint response. Whether the bundled strategy improves clinically meaningful outcomes remains unproven.