PeptiCRAd-1 (CD40L/OX40L oncolytic Ad) + NY-ESO-1/MAGE-A3 peptides drives early immune priming with 40% responses on pembrolizumab

PeptiCRAd-1 is a conditionally replicating oncolytic adenovirus engineered to express CD40L and OX40L and “decorated” with NY-ESO-1 and MAGE-A3 peptides to boost tumor antigen–specific T-cell priming; in VALO-001 (Phase 1, open-label; NCT05492682), patients with injectable, antigen-positive advanced solid tumors received low-dose cyclophosphamide, intratumoral PeptiCRAd-1 prime/boost, and pembrolizumab (n=7 treated; 5 i.t., 2 i.t.+s.c.). No DLTs, treatment-related SAEs, or unexpected safety signals were reported; in the i.t. cohort, innate activation occurred in 3/5, NY-ESO-1/MAGE-A3-specific T-cell responses in 3/5, and increased TILs in 4/5, alongside clinical responses in 2/5 (40%) and disease control in 3/5 (60%)—a small, mixed-tumor signal that’s hard to benchmark vs pembrolizumab alone given variable SOC activity by histology, PD-L1 status, and line of therapy, but is directionally consistent with the hypothesis that “antigen focus + inflammation” may deepen PD-1 benefit. Early i.t.+s.c. dosing produced “markedly stronger” peptide-specific T-cell responses than i.t. alone (numbers not provided), and this cohort remains open (8 additional patients planned); importantly, feasibility is supported by the fact that MAGE-A is more commonly expressed than NY-ESO-1 across many tumor types (e.g., lung adenocarcinoma ~28% MAGE-A-high vs ~4% NY-ESO-1; colorectal adenocarcinoma ~11% vs <1%), which could broaden the addressable antigen-positive population.