Prospective study of Z-100 plus radiotherapy while continuing ICI for progressing non-small cell lung cancer

The relationship between immunity against infectious pathogens and antitumor immunity has regained attention. In vivo studies have demonstrated that the antitumor effects of Z-100, extracted from the Mycobacterium tuberculosis Aoyama strain and containing peptidoglycans, are mediated by CD8⁺ T cell infiltration into tumors. The multicenter prospective NEJ046A study in Japan investigated the immunomodulatory effects of Z-100 in combination with immune checkpoint inhibitors (ICIs) in humans. Patients with advanced NSCLC who had received ICIs and experienced disease progression within the preceding 3 months received palliative radiotherapy (RT) at a total dose in 30 Gy in 10 fractions plus subcutaneous Z-100 twice weekly, while continuing the same ICI therapy. Primary endpoints were safety and the 9-month progression-free survival (PFS) rate. A total of 23 patients with an ECOG performance status of 0 or1 were treated. Immune-related adverse events (irAEs) occurred in 9 patients (39.1%). Grade 3 toxicities were limited to skin disorder (4.3%) and colitis (4.3%). Thirteen patients transitioned from disease progression to stable disease, resulting in a disease control rate of 56.5%. The median PFS was 5.1 months, and the 9-month PFS rate was 15.2% (90% CI 6.3-36.2). The median overall survival after study enrollment was 17.7 months. The authors conclude that ICIs combined with Z-100 and radiotherapy demonstrated tolerable toxicity and preliminary antitumor activity.