Oral Cavity

This Phase 3, multicenter, randomized, open-label study evaluates APG-157 in adults with newly diagnosed locally advanced head and neck squamous cell carcinoma (LA-HNSCC). Two independently powered cohorts are enrolled based on treatment pathway. Cohort A evaluates APG-157 administered as neoadjuvant therapy before curative-intent surgery in participants with resectable oral cavity or oropharyngeal cancer who are medically ineligible for perioperative pembrolizumab. Cohort B evaluates APG-157 administered as induction therapy before definitive chemoradiotherapy and as maintenance therapy after chemoradiotherapy in participants with unresectable or medically inoperable disease. Participants are randomized 1:1 within each cohort to receive APG-157-based treatment or standard-of-care therapy. The primary hypothesis is that APG-157 given before definitive surgery followed by (chemo)radiotherapy improves event-free survival (EFS) compared to surgery and adjuvant (chemo)radiotherapy alone (Cohort A), and that APG-157 given as induction therapy prior to definitive chemoradiotherapy (CRT) followed by maintenance APG-157 improves EFS compared to definitive CRT alone (Cohort B).

In squamous cell carcinoma of the tongue, complete surgical resection of the tumor generally represents the primary treatment strategy. Among factors determining the disease prognostic, the surgical margins status is essential for the continued management of the patient, with or without complementary therapies. Generally, surgical margins are defined using visual and tactile elements. Unfortunately, in 15 to 30 percent of cases, they are defined as positive after histopathological examination, on average 5 to 7 days post-surgery. Techniques have recently been developed to analyze the cancerous and non-cancerous nature of tissues, using the spectral properties of tumor cells. SpiderMass™ is an instrument equipped with a probe for tissue micro-sampling and real-time molecular profile analysis. It is thus ultimately a tool for anatomopathological decision support, for diagnosis and prognosis of the disease. Used in the operating room, SpiderMass™ could also become an innovative surgical tool to precisely define cancerous areas in situ and the margins status in intraoperative conditions. Based on the principle of artificial intelligence, the SpiderMass™ machine must initially learn to recognize pathological tissues versus healthy. This project aims to accomplish this first phase of machine learning for squamous cell carcinoma of the tongue.

The goal of this clinical trial is to assess the safety and tolerability of a virus replicon particle (VRP) encapsulated saRNA encoding IL-12 when injected into in head and neck cancer patients. The main questions being addressed are: The safety and tolerability of intratumoral (IT) injections of VRP-encapsulated saRNA encoding IL-12 (VLPONC-01) The tumor response to IT injections of VLPONC-01 The tumor response due to the combination of IT injections of VLPONC-01 and system IV administration of neoadjuvant pembrolizumab (anti-PD-1) treatment Researchers will compare neoadjuvant pembrolizumab alone to the combination therapy to see if the combination enhances tumor responses.