ESTRO 2021 Abstract Book
appraisal of trial population characteristics is recommended before results are implemented in general practice.
PH-0053 NBTXR3 activated by SBRT combined with nivolumab or pembrolizumab in advanced cancers: phase I trial O. Vivar 1 , C. Shen 2 , J. Frakes 3 , J. Niu 4 , A. Rosenberg 5 , J. Weiss 2 , J. Caudell 6 , K. Jameson 7 , P. Said 8 , T. Seiwert 9 1 Nanobiotix, Medical Affairs, Paris, France; 2 University of North Carolina , School of Medicine, Chapel Hill, USA; 3 Moffitt Cancer Center, Radiation Oncology, Tampa, USA; 4 Banner MD Anderson Cancer Center, Medical Oncology, Gilbert, USA; 5 University of Chicago , Medical Center, Chicago, USA; 6 Moffitt Cancer Center, Radiation Oncology, Tampa, USA; 7 Nanobiotix, Clinical Development, Boston, USA; 8 Nanobiotix, Biometry, Paris, France; 9 Johns Hopkins University, Medical Center, Baltimore, USA Purpose or Objective Immune checkpoint inhibitors (ICIs) have led to improved treatment outcomes in a variety of cancers; however the majority of patients exhibit resistance to ICIs. Overcoming this resistance is a major challenge in immune- oncology. Radiation therapy (RT) has emerged as a promising combination with ICIs since it may act synergistically with ICIs by producing an immunomodulatory effect. NBTXR3, composed of functionalized hafnium oxide nanoparticles, is injected intratumorally and activated by RT. NBTXR3 increases RT energy deposition inside tumor cells and subsequent tumor cell death, without adding toxicity to healthy tissues. Preclinical data demonstrate NBTXR3/RT can trigger a local and systemic anti-tumor immune response and overcome anti-PD-1 resistance. NBTXR3/RT combined with anti-PD-1 may prime the immune system to increase the proportion of ICI responders or convert ICI non-responders to responders. Materials and Methods This multicenter, open-label, phase I trial [NCT03589339] is evaluating NBTXR3/RT/anti-PD-1 in 3 cohorts: (1) Locoregional recurrent or recurrent and metastatic head and neck squamous cell carcinoma (HNSCC) amenable to HN re-irradiation and (2) lung or (3) liver metastases from any primary cancer eligible for anti- PD-1. Stereotactic body RT (SBRT) is delivered at tumor-site specific doses per standard practice. The primary objective is to determine the NBTXR3/RT/anti-PD-1 recommended phase 2 dose in each cohort. Secondary objectives are anti-tumor response (objective response rate), safety, and feasibility of NBTXR3 injection. Results Nine patients have been treated: 3 HNSCC, 4 lung, 2 liver. Overall tumor regression was observed in 8/9 patients of which 7 were anti-PD-1 non-responders. A complete response lasting over 1 year has been observed in the injected lymph node in 1 anti-PD-1 naïve patient. 2 SAEs related to anti-PD-1 and possibly related to NBTXR3 (G5 pneumonitis, G4 hyperglycemia) were observed in 1 anti-PD-1 naïve HNSCC patient and considered DLTs. This patient also experienced 2 other G4 SAEs related to anti-PD-1 (diabetic ketoacidosis, acute kidney injury). SBRT-related safety profile was as expected. Updated safety and efficacy results with additional patients and longer follow-up will be presented. Conclusion Safety data from this first-in-human phase I trial evaluating NBTXR3/RT/anti-PD-1 in patients with advanced cancers show NBTXR3 intratumoral injection is feasible and well-tolerated in HNSCC, lung, and liver. NBTXR3/RT/anti-PD-1 demonstrated promising signs of efficacy and led to tumor regression in patients having progressed on prior anti-PD-1. These data support further development of NBTXR3 in combination with anti- PD-1 as well as other ICIs. PH-0054 Re-Irradiation in head & neck cancer - a pooled analysis of 253 individual cases J. Roesch 1 , M. Oertel 2 , A. Fabian 3 , M. Höck 4 , J. von der Grün 5 , A. Löser 6 , C. Süss 7 , M. Vinsensia 8 , B. Tamaskovics 9 , S. Heß 10 , M. Waltenberger 11 , S. Wegen 12 , M. Trommer 12 , M. Mäurer 13 , D. Medenwald 14 , A. Rühle 15 , L. Käsmann 16 , D. Fleischmann 16 , S. Dobiasch 17 , M. Hecht 18 1 Universitätsklinik Erlangen, Strahlenklinik, Erlangen, Germany; 2 Universitätsklinikum Münster, Klinik für Strahlentherapie - Radioonkologie, Münster, Germany; 3 Universitätsklinikum Schleswig-Holstein, Strahlentherapie, Kiel, Germany; 4 Universitätsklinikum Augsburg, Klinik für Strahlentherapie, Augsburg, Germany; 5 Universitätsklinikum Frankfurt, Klinik für Strahlentherapie, Frankfurt, Germany; 6 Universitätsklinikum Hamburg-Eppendorf, Klinik für Strahlentherapie und Radioonkologie, Hamburg, Germany; 7 Universitätsklinikum Regensburg, Klinik für Strahlentherapie, Regensburg, Germany; 8 Universitätsmedizin Mannheim, Klinik für Strahlentherapie und Radioonkologie, Mannheim, Germany; 9 Universitätsklinikum Düsseldorf, Klinik für Strahlentherapie und Radioonkologie, Düsseldorf, Germany; 10 Universitätsklinikum Würzburg, Klinik für Strahlentherapie, Würzburg, Germany; 11 Technische Universität München, Klinik für Strahlentherapie und Radioonkologie, München, Germany; 12 Universitätsklinikum Köln, Klinik für Strahlentherapie und Radioonkologie, Köln, Germany; 13 Universitätsklinikum Jena, Klinik für Strahlentherapie, Jena, Germany; 14 Universitätsklinikum Halle, Klinik für Strahlentherapie, Halle, Germany; 15 Universitätsklinikum Freiburg, Klinik Für Strahlentherapie, Freiburg, Germany; 16 LMU München, Klinik für Strahlentherapie, München, Germany; 17 Technische Universität München, Klinik für Strahlentherapie, München, Germany; 18 Universitätsklinikum Erlangen, Strahlenklinik, Erlangen, Germany Purpose or Objective Advances in diagnostics, surgery, systemic therapy and radiotherapy has improved quality of life and particularly prognoses of head and neck cancer patients over the last decades. As a consequence, the question of re-treatment in case of local recurrence becomes more important. These patients often suffer from long- term toxicities after multimodal therapy resulting in poor nutritional and general status. Resection of recurrent squamous cell carcinoma of the head and neck (HNSCC) within pre-treated tissue is feasible but due to changed anatomy and fibrosis technically demanding and therefore challenging. Up to today systemic therapy alone is only an option in palliative intent and mostly incapable of long term local control. Thus, re- irradiation should be evaluated in these cases. To determine factors influencing outcome and overall survival,
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