2021 – A new radio-enhancer, PEP503 (NBTXR3), in combination with concurrent chemoradiation in locally advanced or unresectable rectal cancer: The dose-finding part of a phase I/II trial

nano-pub — Thu, 26 May 2022 12:45:30 +0000

Authors

Jaw-Yuan Wang, Ching-Wen Huang, Ming-Yii Huang, Huang-Ming Hu, Wen-Hung Hsu, Hsiang-Yao Shih, Chiao-Yun Chen, Chou-Pin Chen, Jeffrey Yung-Chuan Chao, You-Hsin Chiu

Division of Colorectal Surgery, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung, Taiwan
Department of Radiation Oncology, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung, Taiwan
Division of Gastroenterology, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung, Taiwan Department of Medical Imaging, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung, Taiwan
Division of Colorectal Surgery, Taichung Veterans General Hospital, Taichung, Taiwan
Department of Radiation Oncology, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Radiology, Taichung Veterans General Hospital, Taichung, Taiwan

Summary

Background: PEP503 (as known as NBTXR3) is a novel radio-enhancer composed of functionalized hafnium oxide nanoparticles for a higher energy deposit by radiotherapy comparing to radiotherapy alone without it. A prior phase 3 study for soft tissue sarcoma has demonstrated the clinical benefit. The phase 1b part of the study aimed to test the feasibility of PEP503 intra-tumor injection and examine the safety profile of various dose levels of PEP503 in combination with concurrent chemo-radiation (CCRT) for locally advanced rectal cancers.

Methods: Patients who had rectal adenocarcinoma of T3-4 or locally unresectable disease suitable for neoadjuvant CCRT were eligible. A single administration of PEP503 intra-tumor injection with multiple needle punctures was applied 24 to 72 hours before the start of IMRT or IMAT at 50 Gy in 25 fractions in combination with capecitabine or infusion 5-FU over 5~6 weeks. Dose escalation of 4 levels of PEP503 injected volume was based on 5%, 10%, 15%, and 22% of the baseline tumor volume by MRI. Intra-tumor dispersion of nanoparticles was inspected by CT-scan and the body kinetics evaluation was performed. The total mesorectal excision was planned around 8~12 weeks later after the completion of CCRT. Preliminary efficacy including tumor response after CCRT and the pathological response with tumor regression grade (TRG) after surgery was collected.

Results: Twenty patients were enrolled, with 7, 4, 3, and 6 patients at 5%, 10%, 15%, and 22% dose levels, respectively. An injection procedure-related dose-limiting toxicity of urinary tract infection with sepsis was reported in the first treated patient at 5%. There was no adverse event (AE) or serious AE directly caused by PEP503. The most frequently reported AEs related to CCRT across all dose levels were diarrhea (~45%), WBC decreased (~40%), and dermatitis (~25%), but all were grade 1 or 2. The safety profile of CCRT with PEP503 was similar to it of CCRT without PEP503 for rectal cancer patients. The CT scans, before and after CCRT, displayed the dispersion of PEP503 among different tumor shapes and contours without leakage to the surrounding healthy tissues. In most patients, hafnium was not detected in the circulation in 60 minutes after PEP503 injection and not found in urine. Around 70% of patients showed tumor response after the CCRT and half of the patients receiving surgery achieved good tumor regression (AJCC TRG 0 or TRG 1). In the small phase 1b dose-escalation part of the trial, the dose-dependency of the efficacy endpoints could not be assessed.

Conclusions: Intra-tumor injection of PEP503/NBTXR3 with CCRT is feasible without additional toxicities for rectal cancer patients. The extension phase 2 of the trial to investigate the clinical benefits of PEP503 at 22% of tumor volume is ongoing in Taiwan.

The post 2021 – A new radio-enhancer, PEP503 (NBTXR3), in combination with concurrent chemoradiation in locally advanced or unresectable rectal cancer: The dose-finding part of a phase I/II trial first appeared on Nano Publications.

2017 – Abstract – 35th CFS – Hafnium Oxide Nanoparticles: An Emergent Promising Treatment for Solid Tumors

nano-pub — Tue, 03 Apr 2018 10:15:38 +0000

Authors

L. Levy1, C. Le Tourneau2, P. Sargos3, Le Pechoux4, G. Kantor3, T. De Baere4, A. Le Cesne4, V. Moreno5, E. Calvo5, S. Bonvalot2

1 – Nanobiotix, Paris, France
2 – Institut Curie, Paris, France
3 – Institut Bergonié, Bordeaux, France
4 – Institut Gustave Roussy, Villejuif, France
5 – START Madrid, Spain

Summary

The enclosed abstract was presented at the 35th Annual Chemotherapy Foundation Symposium, New York. The abstract Hafnium oxide nanoparticles: an emergent promising treatment for solid tumors describes the story of hafnium oxide nanoparticles, NBTXR3, from the preclinical to the clinical development up to date.

Preclinical studies have demonstrated increase of cancer cells death in vitro and marked antitumor efficacy in vivo in presence of these nanoparticles (HfO2-NP) exposed to RT, when compared to RT alone. Hafnium oxide nanoparticles efficacy was assessed in cancer epithelial and mesenchymal tumor models and on patient-derived tumor xenografts in nude mice, showing superior anti-tumor effects, over radiation therapy alone in terms of complete response and overall survival. Additionally, in vivo cancer epithelial models in immunocompetent mouse have showed that HfO2-NP + RT triggers immunogenic conversion of the tumor microenvironment and generate an abscopal effect while this effect is not observed with RT alone.

HfO2-NP (NBTXR3), administered as a single intratumoral injection and activated by radiotherapy, is currently evaluated in clinical trials including soft tissue sarcoma (STS) [NCT02379845], head and neck [NCT01946867], prostate [NCT02805894], liver [NCT02721056; NCT02721056] and rectum cancers [NCT02465593]. Patients treated in phases I have had a good tolerance to the product and received radiotherapy as planned, confirming a very good local safety profile.

Besides, consistently with non-clinical studies, preliminary results of the phase II/III in patients with STS, beyond the expected cytotoxic effect induced by NBTXR3 + RT, suggest a release of tumor neoantigens during cancer cell death and stimulation of local immunological effects. This immunogenic cell death might convert “cold” tumor into “hot” tumor. Further analyses are ongoing to reinforce these findings.

The post 2017 – Abstract – 35th CFS – Hafnium Oxide Nanoparticles: An Emergent Promising Treatment for Solid Tumors first appeared on Nano Publications.

Rectal Cancer | Nano Publications

2021 – A new radio-enhancer, PEP503 (NBTXR3), in combination with concurrent chemoradiation in locally advanced or unresectable rectal cancer: The dose-finding part of a phase I/II trial

Authors

Summary

2017 – Abstract – 35th CFS – Hafnium Oxide Nanoparticles: An Emergent Promising Treatment for Solid Tumors

Authors

Summary