Radiation Biology

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SU_43_2434 - Hafnium Oxide Nanoparticles Activated By Radiation Therapy for the Treatment of Solid Tumors

Sunday, October 21
1:15 PM - 2:45 PM
Location: Innovation Hub, Exhibit Hall 3

Hafnium Oxide Nanoparticles Activated By Radiation Therapy for the Treatment of Solid Tumors
C. Le Tourneau1, J. O. Thariat2, E. Chajon Rodriguez3, P. Sargos4, C. Le Pechoux5, G. Kantor6, C. Hoffmann1, V. Moreno Garcia7, T. De Baere5, V. Vendrely8, E. Rio9, A. Lecesne10, A. Gronchi11, P. L. Nguyen12, A. P. Dicker13, T. Y. Seiwert14, Z. Papai15, P. Rutkowski16, and S. Bonvalot1; 1Institut Curie, Paris, France, 2Centre Antoine-Lacassagne, Department of Radiation Oncology, Nice, France, 3Centre Eugène Marquis - Département de Radiothérapie, Rennes, France, 4Department of Radiation Oncology. Institut Bergonie, Bordeaux, France, 5Institut Gustave Roussy, Villejuif, France, 6Department of Radiotherapy, Institut Bergonié, Bordeaux, France, 7START Madrid, Madrid, Spain, 8University Hospital of Bordeaux, Bordeaux, France, 9Institut de Cancérologie de l’Ouest, Nantes, France, 10Service d'Oncologie médicale Gustave Roussy, Villejuif, France, 11Istituto Nazionale Tumori, Milan, Italy, 12Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 13Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, PA, 14University of Chicago, Chicago, IL, 15Magyar Honvedseg Egeszsegugyi Kozpont, Budapest, Hungary, 16Centrum Onkologii-Instytut im. Sklodowskiej-Curie w Warszawie, Warszawa, Poland

Purpose/Objective(s): To improve radiotherapy (RT) in terms of tumor response and to reduce irradiation of healthy tissues, innovative therapeutic approaches are needed. In response, NBTXR3, injectable hafnium oxide nanoparticles, was developed for the treatment of solid tumors. Once injected intratumorally, NBTXR3 can deposit high energy within tumors only when activated by an ionizing radiation source, like current standard RTs. Upon activation, the high energy radiation physically kills the tumor cells by triggering DNA damage and cell destruction improving clinical outcomes. Since its first successful clinical evaluation in a completed phase I trial in patients with locally advanced soft tissue sarcoma, NBTXR3 is currently evaluated in numerous indications worldwide (EU, Asia, US).

Materials/Methods: NBTXR3 was the object of numerous in vitro and in vivo tumor models to determine its mechanism of action, performance and biocompatibility profile. Once they were assessed, NBTXR3 entered clinical development and was administered as a single intratumoral (IT) injection activated by RT. NBTXR3 is clinically evaluated in head and neck [NCT01946867; NCT02901483], prostate [NCT02805894], liver [NCT02721056] and rectum cancers [NCT02465593] with the scope of determining the Recommended Dose or observing any Dose Limiting Toxicities (DLTs) in each indication. A phase II/III trial in soft tissue sarcoma (STS) of the trunk and extremities [NCT02379845] is about to be finalized.

Results: Preclinically, in vitro results showed an increase of cancer cells death and in vivo results demonstrated antitumor efficacy with NBTXR3 + RT compared to RT alone. This physical cell killing could open a potential systemic activity through immune response by triggering immunogenic cell death, reinforcing local effect. Clinically, across the 7 clinical trials and 6 indications, NBTXR3 demonstrated an overall positive safety profile. The numerous types of tumors and different body locations involved in these trials confirmed feasibility of IT injection and persistence of NBTXR3 in the tumor, with no leakage in the surrounding healthy tissues. NBTXR3 antitumor activity is currently evaluated in its first phase II/III in patients with STS. Besides, analysis of tumor biopsies collected pre- and post-radiotherapy suggested a release of tumor antigens during cancer cell death and stimulation of local immunological effects.

Conclusion: NBTXR3 have shown promising results in non-clinical studies with marked antitumor efficacy and in clinical development in terms of safety and preliminary evaluations of efficacy. Considering the preliminary results of the 145 patients injected across all clinical trials, these first-in-class nanoparticles have already proven to be an encouraging innovative treatment in various types of tumors.

Author Disclosure: C. Le Tourneau: Honoraria; Novartis, Bristol-Myers Squibb. Consultant; Amgen, Bristol-Myers Squibb, Merck Serono, AstraZeneca. Travel Expenses; MSD. J.O. Thariat: None. E. Chajon Rodriguez: None. P. Sargos: None. C. Le Pechoux: None. C. Hoffmann: None. V. Moreno Garcia: None. E. Rio: None. A. Lecesne: None. P.L. Nguyen: Honoraria; Bayer. Consultant; Nanobiotix, Infinity Pharmaceuticals, GI Windows, Astellas, Augmenix. Advisory Board; Ferring, Medivation, Genome DX, Dendreon. Stock Options; Augmenix. Program Committee; Genitourinary Cancers Symposium. A.P. Dicker: Research Grant; Radiation Therapy Oncology Group. Travel Expenses; Prostate Cancer Foundation. Chair; Department of Defense. T.Y. Seiwert: Honoraria; Amgen, BMS, Jounce, Merck/ MSD. Travel Expenses; BMS, Jounce, Merck/ MSD. Z. Papai: None.

Juliette Thariat, MD, PhD, MS

Disclosure:
No relationships to disclose.

Biography:
Dr Juliette Thariat, MD, PhD, is a professor in radiation oncology at the cancer Centre of Caen / ARCHADE, France. She trained at MDAnderson, at the European Hospital of Paris, and at the Nice proton center. Her main fields of interest are head and neck, ophthalmology, sarcomas and rare tumors, new indications and innovative radiation techniques (proton therapy / hadrontherapy, SBRT, IMRT). Her lab efforts at the corpuscular physics lab / ENSICAEN-CNRS focus on modeling radiation effects and resolving hadrontherapy uncertainties. She is principal investigator in several national clinical trials. She is president of the French Head and neck Intergroup and co-chairs the GORTEC and REFCOR head and neck groups and supervises the French Inter University Diploma Of innovative irradiation techniques. She serves as an associate editor for several national and international journals. She has written over 290 peer-reviewed publications, 15 book chapters and has over 200 communications in French and International meetings.

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