{"id":2212,"date":"2020-12-17T17:37:36","date_gmt":"2020-12-17T17:37:36","guid":{"rendered":"https:\/\/bibliography.nanobiotix.com\/?p=2212"},"modified":"2022-05-24T16:51:51","modified_gmt":"2022-05-24T15:51:51","slug":"2020-astro-nbtxr3-in-combination-with-anti-pd-1","status":"publish","type":"post","link":"https:\/\/bibliography.nanobiotix.com\/fr\/2020-astro-nbtxr3-in-combination-with-anti-pd-1\/","title":{"rendered":"2020 \u2013 ASTRO \u2013 NBTXR3 in Combination with Anti-PD-1"},"content":{"rendered":"

[vc_row padding_top=\u00a0\u00bb0″ padding_bottom=\u00a0\u00bb0″ section_container_layout=\u00a0\u00bbfull-width\u00a0\u00bb remove_horizontal_padding=\u00a0\u00bbyes\u00a0\u00bb module_type=\u00a0\u00bbbg-color\u00a0\u00bb gutter_size=\u00a0\u00bbyes\u00a0\u00bb equal_height=\u00a0\u00bbyes\u00a0\u00bb bg_color=\u00a0\u00bb#28282e\u00a0\u00bb][vc_column][vc_row_inner padding_top=\u00a0\u00bb0″ padding_bottom=\u00a0\u00bb0″ gutter_size=\u00a0\u00bbyes\u00a0\u00bb equal_height=\u00a0\u00bbyes\u00a0\u00bb][vc_column_inner column_paddings=\u00a0\u00bb105″ column_position_vertical=\u00a0\u00bbmiddle\u00a0\u00bb column_min_height=\u00a0\u00bb700″ column_min_height_sm=\u00a0\u00bb400″ column_min_height_xs=\u00a0\u00bb350″ module_type=\u00a0\u00bbbg-image\u00a0\u00bb bg_image=\u00a0\u00bb102″ mask_fx=\u00a0\u00bbyes-mask\u00a0\u00bb mask_color_mode=\u00a0\u00bbpalette\u00a0\u00bb mask_bg_color_palette=\u00a0\u00bbmain-mask\u00a0\u00bb animation_fx=\u00a0\u00bbyes-animation\u00a0\u00bb animation_delay=\u00a0\u00bb200″ animation_offset_scroll_down=\u00a0\u00bb90″ width=\u00a0\u00bb1\/2″ animation_in=\u00a0\u00bbfadeInUp\u00a0\u00bb][vc_empty_space height=\u00a0\u00bb60px\u00a0\u00bb responsive_lg=\u00a0\u00bbhidden\u00a0\u00bb responsive_md=\u00a0\u00bbhidden\u00a0\u00bb][az_box_icons box_icon_title=\u00a0\u00bbAuthors\u00a0\u00bb box_icon_color_mode=\u00a0\u00bbon-the-fly\u00a0\u00bb icon_visibility=\u00a0\u00bbyes-icon\u00a0\u00bb icon_type=\u00a0\u00bbfont\u00a0\u00bb icon=\u00a0\u00bbfa fa-edit\u00a0\u00bb icon_color_mode=\u00a0\u00bbon-the-fly\u00a0\u00bb icon_size=\u00a0\u00bb50″ box_icon_color=\u00a0\u00bb#ffffff\u00a0\u00bb icon_color=\u00a0\u00bb#ffffff\u00a0\u00bb]Colette Shen1<\/span>, Jessica Frakes2<\/span> Jared Weiss1<\/span>, Jimmy Caudell2<\/span>, Trevor Hackman1<\/span>, Jason A. Akulian1<\/span>, Ghassan El-Haddad2<\/span>, Robert Dixon1<\/span>, Yun Hu3<\/span>, Alexander Pearson4<\/span>, Hampartsoum B. Barsoumian3<\/span>, Maria Angelica Cortez3<\/span>, Katherine Jameson5<\/span>, Patricia Said5<\/span>, James Welsh3<\/span> and Tanguy Seiwert6<\/span>
\n
\n1 \u2013 University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA
\n2 \u2013 Moffitt Cancer Center, Tampa, Florida, USA
\n3 \u2013 Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA
\n4 \u2013 University of Chicago Medicine, Chicago, Illinois, USA
\n5 \u2013 Nanobiotix, SA, France; 6Johns Hopkins Medicine, Baltimore, Maryland, USA
\n<\/span>[\/az_box_icons][vc_empty_space height=\u00a0\u00bb60px\u00a0\u00bb responsive_lg=\u00a0\u00bbhidden\u00a0\u00bb responsive_md=\u00a0\u00bbhidden\u00a0\u00bb][\/vc_column_inner][vc_column_inner column_paddings=\u00a0\u00bb105″ column_position_vertical=\u00a0\u00bbmiddle\u00a0\u00bb module_type=\u00a0\u00bbbg-color\u00a0\u00bb animation_fx=\u00a0\u00bbyes-animation\u00a0\u00bb animation_delay=\u00a0\u00bb300″ animation_offset_scroll_down=\u00a0\u00bb90″ width=\u00a0\u00bb1\/2″ bg_color=\u00a0\u00bb#ffffff\u00a0\u00bb animation_in=\u00a0\u00bbfadeInUp\u00a0\u00bb][vc_empty_space height=\u00a0\u00bb60px\u00a0\u00bb responsive_lg=\u00a0\u00bbhidden\u00a0\u00bb responsive_md=\u00a0\u00bbhidden\u00a0\u00bb][az_box_icons box_icon_title=\u00a0\u00bbSummary\u00a0\u00bb icon_visibility=\u00a0\u00bbyes-icon\u00a0\u00bb icon_type=\u00a0\u00bbfont\u00a0\u00bb icon=\u00a0\u00bbaz-icon az-icon-layers2″ icon_color_mode=\u00a0\u00bbon-the-fly\u00a0\u00bb icon_color=\u00a0\u00bb#28282e\u00a0\u00bb icon_size=\u00a0\u00bb50″]Purpose\/Objectives:<\/strong> Immune checkpoint inhibitors (ICIs) are being increasingly used to improve patient outcomes across different cancer types. However, the response rate to ICIs remains low (~15%), indicating the need for novel strategies to improve treatment outcome. Emerging evidence suggests that radiation therapy (RT) could potentially enhance the antitumor response and provide synergy with ICIs. RT dose and ultimate efficacy are however limited by toxicity related to exposure of healthy tissues. The first-in-class radioenhancer NBTXR3, administered by direct intratumoral injection, is designed at the nanoscale to increase RT dose deposition within tumor cells and RT-dependent tumor cell killing, without increasing toxicity to surrounding normal tissue. Preclinical and early clinical data suggest NBTXR3 activated by RT can trigger an anti-tumor immune response, producing both local and systemic (abscopal) effects. We hypothesize that NBTXR3 activated by RT, in combination with anti-PD-1 therapy (R3\/RT\/PD-1), will act synergistically to maximize the local RT effect and produce a systemic response sufficient to increase the proportion of ICI responders or convert ICI non-responders to responders.<\/p>\n

Materials\/Methods:<\/strong> This multicenter, open-label, phase I trial [NCT03589339] will evaluate safety and tolerability of R3\/RT\/PD-1 in three cohorts: (1) Locoregional recurrent or recurrent and metastatic head and neck squamous cell carcinoma (HNSCC) amenable to re-irradiation of the HN field, (2) Lung metastases, or (3) Liver metastases, both from any primary cancer eligible for anti-PD-1 treatment. Approximately two-thirds of patients in each cohort will be anti-PD-1 non-responders. NBTXR3 injected volume is based on a percentage of baseline gross tumor volume (GTV).<\/p>\n

Results:<\/strong> The primary objective is to determine the R3\/RT\/PD-1 recommended phase 2 dose in each cohort. Secondary objectives are to evaluate anti-tumor response (objective response rate; ORR), safety and feasibility of NBTXR3 injection, and NBTXR3 body kinetic profile. Exploratory objectives will assess biomarkers of R3\/RT\/PD-1 response, including PD-L1 status by IHC, as well as mRNA and cytokine immune marker profiling. Recruitment is ongoing. To date, three patients have been treated, one in cohort 1 and two in cohort 2.<\/p>\n

Conclusions:<\/strong> NBTXR3 activated by RT induces an anti-tumor immune response which may convert immunologically \u201ccold\u201d tumors into \u201chot\u201d tumors. In combination R3\/RT\/PD-1 holds the potential to increase the proportion of ICI responders or convert ICI non-responders to responders.
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Immune checkpoint inhibitors (ICIs) are being increasingly used to improve patient outcomes across different cancer types. However, the response rate to ICIs remains low (~15%), indicating the need for novel strategies to improve treatment outcome. Emerging evidence suggests that radiation therapy (RT) could potentially enhance the antitumor response and provide synergy with ICIs. RT dose and ultimate efficacy are however limited by toxicity related to exposure of healthy tissues. [\u2026]<\/p>\n","protected":false},"author":1,"featured_media":2226,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":[],"categories":[182,183,669,670,668],"tags":[196,197,541,465,618,602,587,621,545,342,624,625,200,555],"aioseo_notices":[],"_links":{"self":[{"href":"https:\/\/bibliography.nanobiotix.com\/fr\/wp-json\/wp\/v2\/posts\/2212"}],"collection":[{"href":"https:\/\/bibliography.nanobiotix.com\/fr\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/bibliography.nanobiotix.com\/fr\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/bibliography.nanobiotix.com\/fr\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/bibliography.nanobiotix.com\/fr\/wp-json\/wp\/v2\/comments?post=2212"}],"version-history":[{"count":1,"href":"https:\/\/bibliography.nanobiotix.com\/fr\/wp-json\/wp\/v2\/posts\/2212\/revisions"}],"predecessor-version":[{"id":2243,"href":"https:\/\/bibliography.nanobiotix.com\/fr\/wp-json\/wp\/v2\/posts\/2212\/revisions\/2243"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/bibliography.nanobiotix.com\/fr\/wp-json\/wp\/v2\/media\/2226"}],"wp:attachment":[{"href":"https:\/\/bibliography.nanobiotix.com\/fr\/wp-json\/wp\/v2\/media?parent=2212"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/bibliography.nanobiotix.com\/fr\/wp-json\/wp\/v2\/categories?post=2212"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/bibliography.nanobiotix.com\/fr\/wp-json\/wp\/v2\/tags?post=2212"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}