2977 - Safety of NBTXR3 Radioenhancer Delivery in Liver Metastases

B. D. Facer¹, C. Shen², J. M. Frakes³, J. Weiss⁴, J. J. Caudell³, A. J. Rosenberg⁵, M. Pracht⁶, Y. Rolland⁷, J. Durand Labrunie⁸, J. P. Bronowicki⁹, V. Vendrely¹⁰, V. V. Croisé-Laurent¹¹, E. Rio¹², D. Rolando¹³, D. Peiffert¹⁴, P. Tyan¹³, O. I. Vivar¹³, E. Deutsch¹⁵, T. De Baere¹⁶, and E. Chajon¹⁷; ¹The Ohio State University, Columbus, OH, ²Department of Radiation Oncology, University of North Carolina, Chapel Hill, NC, ³H. Lee Moffitt Cancer Center and Research Institute, Department of Radiation Oncology, Tampa, FL, ⁴University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC, ⁵Department of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, IL, ⁶Centre Eugene Marquis, Rennes, France, ⁷Centre Eugène-Marquis, Rennes, France, ⁸Gustave Roussy, Villejuif, France, ⁹Hopital de Brabois Adultes, Vandoeuvre-Lès-Nancy, France, ¹⁰Department of Radiation Oncology, Jewish General Hospital, McGill University, Montreal, QC, Canada, ¹¹Institut de Cancérologie de Lorraine, Nancy, France, ¹²Institut de Cancérologie de lOuest René Gauducheau, Nantes, France, ¹³Nanobiotix, Paris, France, ¹⁴Institut de Cancérologie de Lorraine, Vandoeuvre-Les-Nancy, France, ¹⁵Gustave Roussy Cancer Campus, Villejuif, France, ¹⁶Institut Gustave Roussy, Villejuif, France, ¹⁷Eugene Marquis Center, Rennes, France

Purpose/Objective(s): The liver is a common site of cancer metastasis. Approximately 1/3 of patients with metastases at diagnosis have liver metastases. Stereotactic body radiation therapy (SBRT) is a standard treatment option for patients with inoperable liver metastases who may benefit from local treatment. Delivery of an ablative dose while protecting normal organs and preserving a critical volume of functional liver tissue can be challenging, particularly for tumors that are large or near critical structures. In RTOG 0438, 17.4% of patients treated with SBRT for liver metastases had treatment-related Grade 3+ toxicities. NBTXR3, a novel radioenhancer composed of functionalized hafnium oxide nanoparticles administered by a single intratumoral injection, locally increases intratumoral dose deposition without increasing the normal liver dose. NBTXR3 may be a valuable tool for improving the therapeutic ratio in liver SBRT. We report prospective clinical trial data regarding safety of NBTXR3 administration for liver metastases. Materials/

Methods: All patients with liver metastases who were treated with NBTXR3 activated by SBRT were aggregated from two phase I trials, NBTXR3-103 [NCT02721056, completed] and NBTXR3-1100 [NCT03589339, ongoing]. In both studies, patients had 1-2 liver metastases injected with NBTXR3 and treated with SBRT. The NBTXR3 volume ranged from 10-42% of GTV. SBRT dose was recommended 45 Gy / 3 fx or 50 Gy / 5 fx. Success of injection was defined as placement of at least 80% of the planned NBTXR3 volume into the tumor. Outcomes regarding safety (adverse events per CTCAEv5) and efficacy (objective response rate per RECIST v1.1) were gathered.
Results: A total of 20 metastatic tumors in 19 patients were treated with NBTXR3 activated by SBRT. The most common primary tumor sites were head/neck (42.1%), colorectal (21.1%) and lung (10.5%). The median tumor volume was 19.4 cc (1.7—1100.0 cc). The median planned volume of NBTXR3 was 3.3 cc (0.4 – 363.0 cc). Overall injection success rate was 84.2%. Fourteen patients (73.7%) received an NBTXR3 volume of 22-33% of the GTV. There were no SBRT course delays or early terminations. SBRT was delivered as 45 Gy / 3 fx in 16 patients (84.2%) Median follow up was 5.9 months. There were no dose limiting toxicities in any dose level. Grade 3+ toxicities possibly related to NBTXR3 were reported in 3 patients (15.8%): grade 3 bile duct stenosis, grade 3 lymphocytosis, grade 4 anaphylaxis.
Conclusion: NBTXR3 was successfully delivered to the majority of patients. Relative to historical controls, treatment of liver metastases with NBTXR3 activated by SBRT was not associated with an increase in expected grade 3+ toxicities. There were no interruptions to SBRT delivery. These data support the safety of NBTXR3 in the setting of liver metastases as a novel radioenhancer which may allow for dose escalation within the tumor.