TMV Vaccine Alone or With Toripalimab-tpzi for Recurrent Head and Neck Squamous Cell Carcinoma

This is a first-in-human, single-center, open-label Phase 1 study of an autologous tumor membrane vesicle (TMV) vaccine, alone and in combination with toripalimab-tpzi, in adults with loco-regionally recurrent head and neck squamous cell carcinoma (HNSCC) who are candidates for salvage surgery. The TMV vaccine is prepared from each participant's resected or biopsied tumor tissue. Tumor membrane vesicles are modified by protein transfer to display the immunostimulatory molecules IL-12 and B7-1 through glycosylphosphatidylinositol (GPI) anchors, so that tumor antigens and immune-stimulating signals are delivered together at the vaccination site. Phase 1a is a dose escalation of TMV vaccine monotherapy given as adjuvant therapy after salvage surgery. Three dose levels (0.25 mg, 0.5 mg, and 1.0 mg) are administered intradermally every 2 weeks for 3 doses. Up to 6 participants are enrolled at each dose level, and enrollment of the first 2 participants at each dose level is staggered by at least 28 days. Safety and immune stimulating activity are reviewed together to identify the optimal biological dose (OBD). Phase 1b evaluates the TMV vaccine at the OBD in combination with toripalimab-tpzi in participants with PD-L1-positive tumors, using a combined neoadjuvant and post-operative adjuvant approach. Participants receive 2 neoadjuvant vaccine doses (every 2 weeks) and up to 2 doses of toripalimab-tpzi (every 3 weeks) before surgery, followed by 1 adjuvant vaccine dose and toripalimab-tpzi every 3 weeks for up to 1 year or until disease progression. Participants are followed for survival for up to 3 years after treatment initiation.