Metaclipse Therapeutics Corporation
The goal of this clinical trial is to learn if an experimental, personalized cancer vaccine called TMV vaccine is safe and to find the best dose to study in future trials. The study includes adults with head and neck squamous cell carcinoma that has come back in or near the same area after earlier treatment, and who are planning to have surgery to remove it. The study will also test the vaccine together with toripalimab-tpzi, an approved immunotherapy drug. The TMV vaccine is made from each participant's own tumor tissue. Small particles taken from the surface of the tumor cells have 2 immune-boosting proteins added to them, to help the immune system recognize and attack the cancer. The main questions it aims to answer are: * Is the TMV vaccine safe, and what medical problems do participants have after receiving it? * What is the best dose of the TMV vaccine to use in future studies? * Is the TMV vaccine safe when given together with toripalimab-tpzi before and after surgery? The study has 2 parts. In Part 1 (Phase 1a), participants will: * Have tumor tissue collected during their planned surgery, which is used to make their personal vaccine * Receive the vaccine as small injections into the skin every 2 weeks for 3 doses, starting after they recover from surgery * Visit the clinic about once a week for 8 weeks for checkups, blood tests, and safety monitoring * Have scans every 3 months and be followed for up to 3 years The first participants will receive the lowest dose. Later groups will receive higher doses only if the lower dose is found to be safe. In Part 2 (Phase 1b), participants whose tumors test positive for a marker called PD-L1 will: * Have a biopsy to collect tumor tissue for their personal vaccine * Before surgery, receive 2 doses of the vaccine and up to 2 doses of toripalimab-tpzi through a vein * After surgery, receive 1 more dose of the vaccine and continue toripalimab-tpzi every 3 weeks for up to 1 year * Have regular checkups, blood tests, and scans, and be followed for up to 3 years Researchers will also study blood and tumor samples to learn how the immune system responds to the vaccine.
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 sig…
Inclusion Criteria: * Age 18 years or older. * Recurrent, histologically proven squamous cell carcinoma of the head and neck (HNSCC), amenable to curative salvage surgery. EBV- and HPV/p16-positive and -negative tumors are allowed. Squamous cell carcinoma of the oral cavity, larynx, hypopharynx, oropharynx, sinonasal carcinoma, and cancer of unknown primary (squamous cell carcinoma only) are allowed. * Oropharyngeal tumors must have EBV and p16 or HPV testing done. * Tumor tissue must be available and banked (below -70°C) at the time of salvage surgery (Phase 1a) or biopsy (Phase 1b), with th…
Autologous, personalized tumor membrane vesicle (TMV) vaccine prepared from the participant's own tumor tissue, collected at salvage surgery (Phase 1a) or by biopsy (Phase 1b). Tumor membrane vesicles are modified by protein transfer to display the immunostimulatory molecules IL-12 and B7-1 through glycosylphosphatidylinositol (GPI) anchors. Administered by intradermal injection at dose levels of 0.25 mg, 0.5 mg, or 1.0 mg in Phase 1a, and at the optimal biological dose identified in Phase 1a for Phase 1b.
Anti-PD-1 monoclonal antibody administered at 240 mg by intravenous infusion every 3 weeks, for up to 2 doses before salvage surgery and then for up to 1 year after surgery or until disease progression (Phase 1b only).