ESTRO 2025 - Abstract Book

S1796

Clinical – Upper GI

ESTRO 2025

2265

Poster Discussion Nanoray Pancreas: A Phase I Study of NBTXR3 activated by Radiotherapy for Locally Advanced or Borderline Resectable Pancreatic Cancer (LAPC or BRPC) Eugene J. Koay 1 , Suyu Liu 2 , Paola A. Guerrero 3 , Gabriela D. Fuentes 4 , Ethan H. Stokes 4 , Omar I. Vivar 5 , Louis Kayitalire 5 , Matthew H.G. Katz 6 , Naruhiko Ikoma 6 , Ching-Wei D. Tzeng 6 , Rebecca A. Snyder 6 , Michael J. Overman 7 , Shubham Pant 7 , Robert A. Wolff 7 , Milind Javle 7 , Ethan B. Ludmir 1 , Emma B. Holliday 1 , Sonal S. Noticewala 1 , Prajnan Das 1 , Albert C. Koong 1 , Anirban Maitra 3 , Eric P. Tamm 8 , Manoop Bhutani 9 1 Gastrointestinal Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA. 2 Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, USA. 3 Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, USA. 4 Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA. 5 Global Medical Affairs, Nanobiotix, Paris, France. 6 Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA. 7 Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA. 8 Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, USA. 9 Gastroenterology Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, USA Purpose/Objective: The radioresistance and lethality of pancreatic ductal adenocarcinoma are intrinsically tied to aggressive tumor mutations. We evaluated the potential to overcome radioresistance in LAPC and BRPC using NBTXR3, a novel radioenhancer composed of functionalized hafnium oxide nanoparticles administered by intratumoral injection into the gross tumor volume (GTV) and activated by radiotherapy (RT) to enhance tumor cell killing [1]. The primary objective was to determine the recommended phase 2 dose (RP2D) of NBTXR3. Secondary objectives included measuring anti-tumor effects. Material/Methods: The study used a Bayesian optimal interval design (BOIN) with two parts: dose-finding for RP2D (NBTXR3 at 33% of GTV [level 1] or at 42% of GTV [level 2]) and cohort expansion at RP2D. In part 1 (n=10), eligibility criteria included only patients with LAPC with no evidence of distant metastasis (DM) after 2-6 months of chemotherapy. Part 2 (n=12) allowed LAPC or BRPC. NBTXR3 was intratumorally injected once prior to RT via endoscopic ultrasound guidance. All patients received 45 Gy in 15 fractions to GTV (BED of 58.5 Gy 10 ) with intensity modulated RT. Efficacy was measured by RECIST v1.1 criteria and the Kaplan Meier method. Serial blood was collected to measure CA19-9 kinetics and circulating tumor mutational burden (cTMB) using a targeted mutation panel. Results: 22 patients (median 63 yrs [39-81], 10 males, 12 females, 20 LAPC, 2 BRPC) completed protocol therapy with median follow up of 11.9 mos (range 3-40.7). Dose-limiting toxicities (DLTs) were absent in part 1 (level 1 dose for first patient and level 2 dose for subsequent 9 patients). Grade 3 DLTs were transiently observed in 3 of 12 patients in part 2 at the level 2 dose. After receipt of NBTXR3/RT, 10 of the 22 patients had local progression, with median local progression free survival (LPFS) of 13.3 mos; 14 of the 22 patients had DM, with median DM PFS of 10.7 mos; and 13 of the 22 patients died, with median OS of 16.3 mos. Median OS from diagnosis was 23 mos (95% confidence interval, 17 mos—NA). Two patients had R0 resections with 0% and 15% viable tumor cells remaining. In exploratory analyses, cTMB kinetics associated with LPFS (p<0.05), and CA19-9 normalization associated with OS (p<0.05). Conclusion: NBTXR3/RT is safe for patients with LAPC and BRPC with an RP2D of 42% of GTV. Oncologic outcomes are encouraging and warrant further investigation in a phase 2 trial, with incorporation of cTMB and CA19-9 as correlative biomarkers.

Keywords: pancreatic cancer, NBTXR3, radiation