Elderly Patients | Nano Publications

2020 – ESTRO – NBTXR3 for the Treatment of Locally Advanced HNSCC

nano-pub — Sun, 20 Dec 2020 12:45:12 +0000

Authors

Christophe Le Tourneau1, Valentin Calugaru1, Edith Borcoman7, Victor Moreno2, Emiliano Calvo3, Xavier Liem4, Sébastien Salas5, Bernard Doger2, Thomas Jouffroy1, Xavier Mirabel4, Jose Rodriguez1, Anne Chilles1, Katell Bernois6, Mercedes De Rink6, Nicolas Fakhry5, Stéphanie Wong Hee Kam5, Caroline Hoffmann1

1 – Institut Curie, Paris, France
2 – START – Fundación Jiménez Díaz, Madrid, Spain
3 – START – Hospital Sanchinarro, Madrid, Spain
4 – Oscar Lambret Center, Lille, France
5 – Hôpital Timone, Marseille, France
6 – Nanobiotix, SA, France
7 – Department of Drug Development and Innovation (D3i), Institut Curie, Paris, France
8 – INSERM U900 Research unit, Saint-Cloud, France
9 – Paris-Saclay University, Paris, France

Summary

Purpose/Objective: Elderly and frail patients (pts) with head and neck squamous cell carcinoma (HSNCC) remain a challenging population to manage due to the lack of evidence-based recommendations. Despite representing approximately 20% of the HNSCC population no consensus exists on the optimal treatment for these pts with locally advanced (LA) disease, vulnerable to current standard of care treatment-induced toxicities. New approaches are thus needed to improve clinical outcomes without adding toxicity. NBTXR3 hafnium oxide nanoparticles injected intratumorally may represent such an option. Otherwise inert, this first-in-class radioenhancer augments the radiotherapy (RT) dose within tumor cells when activated by RT, increasing tumor cell death compared to RT alone. The results presented here demonstrate the feasibility and safety of NBTXR3 activated by RT in elderly patients, a population with few therapeutic options.

Material/Methods: Patients with Stage III-IV LA HNSCC of the oropharynx or oral cavity ineligible for platinum-based chemoradiation received a single intratumoral injection of NBTXR3 and intensity modulated radiation therapy (IMRT; 70 Gy/35 fractions/7 weeks). This is a 3+3 design dose escalation study to test NBTXR3 dose levels equivalent to 5, 10, 15, and 22% of baseline theoretical tumor volume, followed by a dose expansion. Primary endpoints include Recommended Phase 2 Dose (RP2D) determination and early dose limiting toxicities (DLT). NBTXR3 presence in surrounding healthy tissues and anti-tumor activity (RECIST 1.1) were also evaluated.

Results: Enrollment was completed at all dose levels: 5% (3 pts), 10% (3 pts), 15% (5 pts), and 22% (8 pts). No early DLT or SAE related to NBTXR3 or injection were observed. One G1 AE (asthenia; 22%) related to NBTXR3 and four AEs (G2 oral pain, G1 tumor hemorrhage, asthenia, and injection site hemorrhage) related to injection were observed. RT-related toxicity was as expected with IMRT. The RP2D was determined to be 22% by the DSMB. CT-scan assessment demonstrated localization of NBTXR3 intratumorally without presence in surrounding healthy tissues. At a median follow-up of 231 days, 9/13 (2 unconfirmed) evaluable pts receiving doses ≥10%, achieved a complete response of the treated tumors. The final dose escalation safety and efficacy results will be presented herein.

Conclusion: NBTXR3 was well tolerated at all tested doses and demonstrated preliminary anti-tumor activity. The dose expansion part at the RP2D is ongoing. These results highlight the potential of NBTXR3 as a novel treatment option for elderly pts with LA HNSCC and address an unmet medical need.

The post 2020 – ESTRO – NBTXR3 for the Treatment of Locally Advanced HNSCC first appeared on Nano Publications.

2020 – ASTRO – NBTXR3 in HNSCC

nano-pub — Fri, 18 Dec 2020 12:19:04 +0000

Authors

Christophe Le Tourneau1, Valentin Calugaru2, Edith Borcoman1, Victor Moreno3, Emiliano Calvo4, Xavier Liem5, Sébastien Salas6, Bernard Doger3, Olivier Choussy7, Maria Lesnik7, Xavier Mirabel5, Nathalie Badois8, Samar Krihli2, Josefin Blomkvist9, Nicolas Fakhry6, Stéphanie Wong Hee Kam6, Caroline Hoffmann8

1 – Department of Drug Development and Innovation (D3i), Institut Curie, Paris, France
2 – Department of Radiation Therapy, Institut Curie, Paris, France
3 – START – Fundación Jiménez Díaz, Madrid, Spain
4 – START – Hospital Sanchinarro, Madrid, Spain
5 – Oscar Lambret Center, Lille, France
6 – Hôpital Timone, Marseille, France
7 – Department of Surgical Oncology, Institut Curie, Paris, France
8 – Department Medical Oncology, Institut Curie, Paris, France
9 – Nanobiotix, SA, France

Summary

Purpose/Objectives: Concurrent chemoradiation (CRT) with high dose cisplatin or cetuximab in case of contra-indication to cisplatin is the standard of care non-surgical approach for patients (pts) with locally advanced head and neck squamous cell carcinoma (LA HNSCC). Older age is a contra-indication to cisplatin and survival in older pts might not improve with cetuximab. The development of new treatment options for elderly pts with LA HNSCC is therefore urgently needed. NBTXR3, hafnium oxide nanoparticles that enhance the efficacy of radiotherapy (RT) by locally increasing the deposited dose, may benefit this patient population. In this phase I clinical trial we aimed to evaluate the feasibility and safety of intratumoral (IT) NBTXR3 injection prior to RT in elderly pts with LA HNSCC.

Materials/Methods: Patients with stage III-IV LA HNSCC of the oropharynx or oral cavity ineligible for platinum-based CRT received a single IT injection of NBTXR3 into a selected primary tumor followed by intensity modulated RT (IMRT; 70 Gy/35 fractions/7 weeks) [NCT01946867]. The study used a 3+3 dose escalation design to test NBTXR3 dose levels of 5, 10, 15, and 22% of baseline tumor volume, followed by a dose expansion at the Recommended Phase 2 Dose (RP2D). Primary endpoints included RP2D determination, and early dose limiting toxicities (DLT). NBTXR3 intratumoral bioavailability and anti-tumor activity (RECIST 1.1) were also evaluated.

Results: Enrollment at all dose levels has been completed: 5% (3 pts), 10% (3 pts), 15% (5 pts), and 22% (8 pts). There were no observed early DLT or SAE related to NBTXR3 or injection. Median follow-up from NBTXR3 administration is currently 7.6 months. One Grade 1 AE related to NBTXR3 at the 22% dose level and 4 Grade 1-2 AEs related to the injection at the 15% and 22% dose levels were observed. IMRT-related toxicity was as expected. NBTXR3 was well dispersed throughout the tumor and not in surrounding healthy tissues, as assessed by CT-scan. The RP2D was determined to be 22%. Preliminary efficacy was evaluated in pts who received the intended dose of NBTXR3 and RT. Among 13 evaluable pts at doses ≥10%, 9 pts (69%) achieved a complete response (2 unconfirmed) of the injected tumor and 5 pts (38%)achieved an overall complete response. Preliminary safety and efficacy data of the dose expansion cohort at the RP2D will also be presented.

Conclusions: NBTXR3 was well tolerated at all tested doses and when activated by RT demonstrated promising preliminary anti-tumor activity. Recruitment in the dose expansion cohort is ongoing. These results highlight the potential of NBTXR3 activated by RT as a novel treatment option for elderly pts with LA HNSCC and address an unmet medical need.

The post 2020 – ASTRO – NBTXR3 in HNSCC first appeared on Nano Publications.

2020 – MHNCS – NBTXR3 for locally advanced HNSCC

nano-pub — Mon, 20 Jul 2020 12:22:52 +0000

Authors

C. Le Tourneau1, V. Calugaru1, E. Borcoman1, V. Moreno2, E. Calvo3, X. Liem4, S. Salas5, B. Doger3, T. Jouffroy1, X. Mirabel4, J. Rodriguez1, A. Chilles1, K. Bernois6, M. De Rink6, E. Baskin-Bey6, N. Fakhry7, S. Wong Hee Kam8, and C. Hoffmann1

1 – Institut Curie, Paris, France
2 – Hospital Fundacio´n Jimenez Diaz, Madrid, Spain
3 – START Madrid, Madrid, Spain
4 – Centre Oscar Lambret, Lille, France
5 – Assistance Publique Hôpitaux de Marseille, Timone Hospital, Marseille, France
6 – Nanobiotix, Paris, France
7 – Hôpital Timone, Marseille, France
8 – Hôpital Timone, APHM, Marseille, France

Summary

Purpose/Objectives: Elderly and/or frail patients (pts) with head and neck squamous cell carcinoma (HSNCC) remain a challenging to manage and neglected population regarding clinical trials and data generation to support treatment choices. Despite representing 20% of the HNSCC population no consensus exists on what is the optimal treatment for these pts with locally advanced (LA) disease, vulnerable to treatment-induced toxicities with the current standard of care. New approaches are needed to improve clinical outcomes without adding toxicity. NBTXR3 hafnium oxide nanoparticles injected intratumorally may represent such an option. Otherwise inert; this first-in-class radioenhancer, augments the radiotherapy (RT) dose within tumor cells when activated by RT, increasing tumor cell death compared to RT alone. The results presented here demonstrate the feasibility and safety of NBTXR3 activated by RT in elderly/frail patients, a population with few therapeutic options.

Material/Methods: Elderly/frail pts received a single intratumoral injection of NBTXR3 and intensity modulated radiation therapy (IMRT; 70 Gy/35 fractions/7 weeks). The study was a 3 + 3 dose escalation to test the NBTXR3 dose equivalent to 5, 10, 15, and 22% of baseline theoretical tumor volume, followed by a dose expansion. Primary endpoints include Recommended Phase 2 Dose (RP2D) determination and early dose limiting toxicities (DLT). NBTXR3 presence in surrounding healthy tissues and anti-tumor activity (RECIST 1.1) were also evaluated.

Results: Enrollment was completed at all dose levels: 5% (3 pts), 10% (3 pts), 15% (5 pts), and 22% (8 pts). No early DLT or SAE related to NBTXR3 or injection were observed. One G1 AE (asthenia; 22%) related to NBTXR3 and four AEs (G2 oral pain, G1 tumor hemorrhage, asthenia, and injection site hemorrhage) related to injection were observed. RT-related toxicity was as expected with IMRT. The RP2D was determined to be 22%. CT-scan assessment demonstrated localization of NBTXR3 intratumorally without presence in surrounding healthy tissues. At a median follow-up of 231 days, 9/13 (2 unconfirmed) evaluable pts receiving doses ≥10%, achieved a complete response of the treated tumors. The final dose escalation safety and efficacy results will be presented herein.

Conclusion: NBTXR3 was well tolerated at all tested doses and demonstrated preliminary anti-tumor activity. A dose expansion phase at the RP2D is ongoing. These results highlight the potential of NBTXR3 as a novel treatment option for elderly/frail pts with LA HNSCC and address an unmet medical need.

The post 2020 – MHNCS – NBTXR3 for locally advanced HNSCC first appeared on Nano Publications.

2021 – Eur J Cancer – NBTXR3 Phase I in HNSCC

nano-pub — Fri, 12 Mar 2021 12:12:10 +0000

Authors

Caroline Hoffmann1, Valentin Calugaru2, Edith Borcoman3, Victor Moreno4, Emiliano Calvo5, Xavier Liem6, Sébastien Salas7, Bernard Doger4, Thomas Jouffroy1, Xavier Mirabel 6, Jose Rodriguez1, Anne Chilles2, Katell Bernois8, Mikaela Dimitriu8, Nicolas Fakhry9, Stéphanie Wong Hee Kam7, Christophe Le Tourneau10

1 – Department of Surgery, Institut Curie, Paris, France
2 – Department of Radiation Oncology, Institut Curie, Paris, France
3 – Department of Drug Development and Innovation (D3i), Institut Curie, Paris, France
4 – START – Fundación Jiménez Díaz, Madrid, Spain
5 – START – Hospital Sanchinarro, Madrid, Spain
6 – Oscar Lambret Center, Lille, France
7 – Hôpital Timone, Marseille, France
8 – Nanobiotix, SA, France
9 – Hôpital Conception, Aix-Marseille University, Marseille, France
10 – Department of Drug Development and Innovation (D3i), Institut Curie, Paris, France; INSERM U900 Research Unit, Saint-Cloud, France; Paris-Saclay University, Paris, France

Summary

Purpose: This phase I study assessed the safety of first-in-class radioenhancer nanoparticles, NBTXR3, in elderly or frail patients with locally advanced head and neck squamous cell carcinoma (HNSCC), ineligible for chemoradiation.

Methods: Patients with stage III or IVA (American Joint Committee on Cancer (AJCC) guidelines, 7th edition, 2010) HNSCC of the oral cavity or oropharynx, aged ≥70 or ≥65 years and ineligible to receive cisplatin, amenable to radiotherapy (RT) with curative intent, received NBTXR3 as a single intratumoural (IT) injection followed by activation by intensity-modulated radiation therapy (IMRT; 70 Gy). The NBTXR3 dose corresponded to a percentage of the baseline tumour volume, measured by magnetic resonance imaging. The primary objectives were to determine the recommended phase II dose (RP2D), dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD). Safety and tolerability were assessed using National Cancer Institute CTCAE version 4.0. Antitumour activity was assessed by Response Evaluation Criteria in Solid Tumours 1.1.

Results: Nineteen patients were enrolled: 3 at the dose level of 5%, 3 at the dose level of 10%, 5 at the dose level of 15% and 8 at the dose level of 22% of the tumour volume. The MTD was not reached, and no DLTs or serious adverse event (SAEs) related to NBTXR3 were observed. Four adverse events related to NBTXR3 and/or the IT injection were reported (grade I–II). NBTXR3 remained in the injected tumour throughout RT, with no leakage in the surrounding healthy tissues. Specific RT-related toxicity was as expected with IMRT. The RP2D was determined as 22% baseline tumour volume. Preliminary signs of antitumour activity were observed.

Conclusion: Intratumoural injection of NBTXR3 followed by IMRT is feasible and demonstrated a good safety profile, supporting further evaluation at the RP2D in this patient population.

The post 2021 – Eur J Cancer – NBTXR3 Phase I in HNSCC first appeared on Nano Publications.