{"id":1897,"date":"2021-05-26T16:45:00","date_gmt":"2021-05-26T20:45:00","guid":{"rendered":"https:\/\/nanobiotix.com\/resource\/results-from-the-phase-i-dose-escalation-study-of-the-radiation-enhancer-nbtxr3-for-the-treatment-of-hcc-and-liver-metastases\/"},"modified":"2024-10-29T08:50:15","modified_gmt":"2024-10-29T12:50:15","slug":"results-from-the-phase-i-dose-escalation-study-of-the-radiation-enhancer-nbtxr3-for-the-treatment-of-hcc-and-liver-metastases","status":"publish","type":"resource","link":"https:\/\/nanobiotix.com\/fr\/resource\/results-from-the-phase-i-dose-escalation-study-of-the-radiation-enhancer-nbtxr3-for-the-treatment-of-hcc-and-liver-metastases\/","title":{"rendered":"Results from the phase I dose-escalation study of the radiation enhancer NBTXR3 for the treatment of HCC and liver metastases"},"content":{"rendered":"

[vc_row padding_top=”0″ padding_bottom=”0″ section_container_layout=”full-width” remove_horizontal_padding=”yes” module_type=”bg-color” gutter_size=”yes” equal_height=”yes” bg_color=”#28282e”][vc_column][vc_row_inner padding_top=”0″ padding_bottom=”0″ gutter_size=”yes” equal_height=”yes”][vc_column_inner column_paddings=”105″ column_position_vertical=”middle” column_min_height=”700″ column_min_height_sm=”400″ column_min_height_xs=”350″ module_type=”bg-image” bg_image=”99″ mask_fx=”yes-mask” mask_color_mode=”palette” mask_bg_color_palette=”main-mask” animation_fx=”yes-animation” animation_delay=”200″ animation_offset_scroll_down=”90″ width=”1\/2″ animation_in=”fadeInUp”][vc_empty_space height=”60px” responsive_lg=”hidden” responsive_md=”hidden”][az_box_icons box_icon_title=”Authors” box_icon_color_mode=”on-the-fly” icon_visibility=”yes-icon” icon_type=”font” icon=”fa fa-edit” icon_color_mode=”on-the-fly” icon_size=”50″ box_icon_color=”#ffffff” icon_color=”#ffffff”]Thierry De Baere, Marc Pracht, Yann Rolland, Jerome Durand-Labrunie, Nicolas Jaksic, France Nguyen, Jean-Pierre Bronowicki, Veronique Vendrely, Val\u00e9rie Crois\u00e9-Laurent, Emmanuel Rio, Samuel Le Sourd, Patricia Said, Pierre Gustin, Christophe Perret, Didier Peiffert, Eric Deutsch, Enrique Chajon Institut Gustave Roussy, Villejuif, France; Oncodermatology Unit, Eugene Marquis Center CHU-CLCC, Rennes, France; Centre Eug\u00e8ne-Marquis, Rennes, France; Centre Eug\u00e8ne Marquis, Rennes, France; INSERM 954, CHU de Nancy, Universit\u00e9 de Lorraine, Nancy, France; CHU Bordeaux, Bordeaux, France; Institut de Canc\u00e9rologie de Lorraine, Nancy, France; ICO-Site Ren\u00e9 Gauducheau, Saint-Herblain, France; Nanobiotix, Paris, France; Institut de Canc\u00e9rologie de l\u2019Ouest, Nantes, France; H\u00f4pital de Brabois Adultes, Vand\u0153uvre-L\u00e8s-Nancy, France <\/span>[\/az_box_icons][vc_empty_space height=”60px” responsive_lg=”hidden” responsive_md=”hidden”][\/vc_column_inner][vc_column_inner column_paddings=”105″ column_position_vertical=”middle” module_type=”bg-color” animation_fx=”yes-animation” animation_delay=”300″ animation_offset_scroll_down=”90″ width=”1\/2″ bg_color=”#ffffff” animation_in=”fadeInUp”][vc_empty_space height=”60px” responsive_lg=”hidden” responsive_md=”hidden”][az_box_icons box_icon_title=”Summary” icon_visibility=”yes-icon” icon_type=”font” icon=”az-icon az-icon-layers2″ icon_color_mode=”on-the-fly” icon_color=”#28282e” icon_size=”50″]Background:<\/b> NBTXR3, a first-in-class radioenhancer composed of functionalized hafnium oxide nanoparticles, is administered by one time intratumoral injection (ITI) and activated by radiotherapy (RT), such as stereotactic body RT (SBRT). NBTXR3 increases RT energy deposit inside tumor cells and subsequently increases tumor cell death compared to RT alone, while sparing healthy tissues. SBRT is well-tolerated in hepatocellular carcinoma (HCC) or liver metastases (mets) and a valuable alternative for patients not eligible for surgery or radiofrequency ablation. However, energy dose deposit to tumor cells is limited due to potential toxicity to surrounding healthy tissues. Patients with unresectable liver cancers including patients with liver or renal dysfunction might benefit from NBTXR3. A Phase 1 clinical trial was conducted to evaluate the safety and Recommended Phase 2 Dose (RP2D) of NBTXR3 activated by SBRT [NCT02721056] in these patients, here we report the results. Methods:<\/b> A 3+3 dose escalation scheme tested 5 NBTXR3 levels: 10, 15, 22, 33, and 42% of baseline tumor volume. NBTXR3 ITI was followed by SBRT (45 Gy \/ 3 fractions \/ 5-7 days or 50 Gy \/ 5 fractions \/ up to 15 days) in patients with HCC or liver mets. Primary endpoints included RP2D determination and early DLT incidence. Secondary endpoints include safety profile, liver disease scores evolution, and early efficacy by response rate (mRECIST for HCC\/RECIST 1.1 for liver mets). Results:<\/b> 23 patients were treated: 6 patients at 10% (2 SBRT doses tested due to organ constraints), 4 patients each at 15% and 22% (due to fiducial displacement and ITI shift), 3 patients at 33% and 6 patients at 42%. No early DLT was observed at any dose level. 1 SAE (grade 3 late onset bile duct stenosis) related to NBTXR3 and RT occurred at 22%. There were 11 AEs related to NBTXR3 and\/or ITI, of which grade 3 AEs were: 2 abdominal pain (ITI related; 15%) and 1 late onset bile duct stenosis (22%), lesion close to the bile duct. No NBTXR3 or ITI related grade 4-5 AEs were observed. RT related AEs were as expected with SBRT. No clinically meaningful changes in Child-Pugh score or APRI were observed post-treatment. CT-scan showed NBTXR3 present within the tumor without leakage to surrounding healthy tissues. Best observed responses (MRI) in injected target lesions from HCC patients (n = 15) were 5 CRs (33.3%), 5 PRs(33.3%), 1 SD (6.7%), 2 NE (13.3%), 2 patients did not have post baseline MRI and for liver mets (n = 8) were 5 PRs (62.5%), 2 SD (25.0%) and 1 NE (12.5%). Conclusions:<\/b> No early DLTs were observed and NBTXR3 demonstrated a good safety and tolerability profile. The RP2D was determined to be 42% of tumor volume. Initial efficacy is promising and highlights the potential for NBTXR3 to address an unmet medical need in patients with unresectable primary or metastatic liver cancers.[\/az_box_icons][vc_empty_space height=”60px” responsive_lg=”hidden” responsive_md=”hidden”][\/vc_column_inner][\/vc_row_inner][\/vc_column][\/vc_row]<\/p>\n","protected":false},"featured_media":0,"menu_order":0,"template":"","meta":{"_acf_changed":false,"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"default","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","ast-disable-related-posts":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"wds_primary_resource_type":0,"wds_primary_data_type":0,"wds_primary_indication":0,"wds_primary_platform_type":0,"footnotes":""},"resource_type":[31,23],"data_type":[25],"indication":[32],"platform_type":[36],"class_list":["post-1897","resource","type-resource","status-publish","hentry","resource_type-abstracts","resource_type-no-rights","data_type-clinical","indication-liver","platform_type-nbtxr3"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanobiotix.com\/fr\/wp-json\/wp\/v2\/resource\/1897","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/nanobiotix.com\/fr\/wp-json\/wp\/v2\/resource"}],"about":[{"href":"https:\/\/nanobiotix.com\/fr\/wp-json\/wp\/v2\/types\/resource"}],"version-history":[{"count":0,"href":"https:\/\/nanobiotix.com\/fr\/wp-json\/wp\/v2\/resource\/1897\/revisions"}],"wp:attachment":[{"href":"https:\/\/nanobiotix.com\/fr\/wp-json\/wp\/v2\/media?parent=1897"}],"wp:term":[{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanobiotix.com\/fr\/wp-json\/wp\/v2\/resource_type?post=1897"},{"taxonomy":"data_type","embeddable":true,"href":"https:\/\/nanobiotix.com\/fr\/wp-json\/wp\/v2\/data_type?post=1897"},{"taxonomy":"indication","embeddable":true,"href":"https:\/\/nanobiotix.com\/fr\/wp-json\/wp\/v2\/indication?post=1897"},{"taxonomy":"platform_type","embeddable":true,"href":"https:\/\/nanobiotix.com\/fr\/wp-json\/wp\/v2\/platform_type?post=1897"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}