1199TiP Phase I trial of in situ vaccination with autologous CCL21-modified dendritic cells (CCL21-DC) combined with pembrolizumab for advanced NSCLC

Effective immunotherapy options are lacking for patients with advanced NSCLC who progress on a PD-(L)1 inhibitor and those that EGFR or ALK positive after progression TKI therapy. One potential approach to improve ICI efficacy is promote cytolytic T cell infiltration into tumors. This can be accomplished via in situ vaccination functional antigen presenting cells which take advantage of the full repertoire tumor antigens convert lymph node-like environment promoting both local systemic activation. The chemokine CCL21 promotes co-localization naive antigen-experienced dendritic (DCs) facilitate Our preclinical studies phase I trial intratumoral (IT) administration DC genetically modified overexpress (CCL21-DC) revealed augmentation presentation situ, resulting antitumor immunity. However, increased PD-L1 expression was observed following therapy some patient tumors, suggesting tumor-mediated impairment function may forestalling more robust CCL21-DC mediated response. Therefore, we conducting trial, combining IT pembrolizumab NSCLC. Phase I, dose-escalating, followed by dose expansion. Maximum 24 (9-12 escalation + 12 expansion) stage IV will evaluated have tumors accessible injection either (1) EGFR/ALK wild-type (2) mutant Three injections autologous (days 0, 21, 42) concurrently administered pembrolizumab, q3wk pembrolizumab. Primary objective safety determination maximum tolerated (MTD) (5x106, 1x107, 3x107) when combined expansion response rate at MTD. Secondary objectives include adverse event profiling drug target activity immune monitoring studies. NCT03546361, currently open enrollment. NCT03546361. authors. Merck, LUNGevity, NIH-NCI, DOD, California Institute Regenerative Medicine (CIRM).