Phase 2 CADI-05 poly‑TLR agonist (heat‑killed Mycobacterium indicus pranii immunotherapy) + pembrolizumab PD‑1 inhibitor in resectable LA‑HNSCC.

This single-site, open-label neoadjuvant study at Fox Chase Cancer Center tests whether adding CADI-05—an intradermal innate-immune activator described by NCI as a poly‑TLR agonist, polyantigenic vaccine made from heat‑killed Mycobacterium indicus pranii—can deepen anti-tumor immune priming when paired with pembrolizumab (Merck’s PD‑1–blocking monoclonal antibody). Adults with surgically resectable, locally advanced HNSCC (stage III/IVA; including HPV-negative disease and HPV-positive T4/N0–2/M0 cohorts) receive pembrolizumab IV on weeks 1 and 4 plus weekly intradermal CADI‑05 for 5 weeks, then proceed to surgery around weeks 6–7, followed by safety follow-up. The scientific angle is “in situ vaccination”-style immune conditioning: stimulate antigen presentation and Th1-skewed immunity via TLR signaling, then release PD‑1 brakes to expand tumor-reactive T cells. For resectable LA‑HNSCC today, care is curative-intent surgery plus risk-adapted adjuvant radiotherapy ± cisplatin; and (since June 12, 2025) pembrolizumab is FDA-approved as neoadjuvant then adjuvant therapy for PD‑L1 CPS ≥1 tumors, making this trial a true add-on to an increasingly immunotherapy-inclusive perioperative standard.