{"id":3086,"date":"2022-06-06T08:47:18","date_gmt":"2022-06-06T07:47:18","guid":{"rendered":"https:\/\/bibliography.nanobiotix.com\/?p=3086"},"modified":"2022-06-06T08:47:51","modified_gmt":"2022-06-06T07:47:51","slug":"2021-nbtxr3-activated-by-sbrt-combined-with-nivolumab-or-pembrolizumab-in-patients-with-advanced-cancers-phase-i-trial-2","status":"publish","type":"post","link":"https:\/\/bibliography.nanobiotix.com\/fr\/2021-nbtxr3-activated-by-sbrt-combined-with-nivolumab-or-pembrolizumab-in-patients-with-advanced-cancers-phase-i-trial-2\/","title":{"rendered":"2021 \u2013 NBTXR3 activated by SBRT combined with nivolumab or pembrolizumab in patients with advanced cancers: phase I trial"},"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\u00bb99″ 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]C. Shen1<\/span>, J.M. Frakes2<\/span>, J. Niu3<\/span>, A.J. Rosenberg4<\/span>, J. Weiss5<\/span>, J.J. Caudell6<\/span>, K. Jameson7<\/span>, P. Said8<\/span>, and T.Y. Seiwert9<\/span>
\n
\n1 \u2013 Department of Radiation Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC,
\n2 \u2013 H. Lee Moffitt Cancer Center and Research Institute, Department of Radiation Oncology, Tampa, FL,
\n3 \u2013 Banner MD Anderson Cancer Center, Gilbert, AZ,
\n4 \u2013 Department of Medicine, Section of Hematology\/Oncology, University of Chicago Medical Center, Chicago, IL,
\n5 \u2013 University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC,
\n6 \u2013 Moffitt Cancer Center, Tampa, FL,
\n7 \u2013 Nanobiotix Corp, Cambridge, MA,
\n8 \u2013 Nanobiotix, Paris, France,
\n9 \u2013 Department of Medicine, Section of Hematology\/Oncology, The University of Chicago Medicine, Chicago, IL
\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″]Introduction:<\/b> Immune checkpoint inhibitors (ICIs) have improved treatment outcomes in a variety of cancers; however the majority of patients (pts) exhibit resistance. Emerging evidence suggests radiation therapy (RT) can enhance response to ICIs by producing an immunomodulatory effect. NBTXR3, composed of functionalized hafnium oxide nanoparticles, is injected intratumorally and activated by RT. NBTXR3 increases RT energy deposition inside tumor cells and subsequent tumor cell death, without adding toxicity to healthy tissues. Preclinical data demonstrate NBTXR3\/RT can trigger a local and systemic anti-tumor immune response and overcome anti-PD-1 resistance. NBTXR3\/RT combined with anti-PD-1 may prime the immune system to increase the proportion of ICI responders or convert ICI non-responders to responders.<\/p>\n

Materials and Methods:<\/b> A multicenter, open-label, phase I trial [NCT03589339] evaluating NBTXR3\/SBRT\/anti-PD-1 (nivolumab or pembrolizumab) in 3 cohorts (1) Locoregional recurrent or recurrent and metastatic HNSCC amenable to HN re-irradiation, (2) lung or (3) liver metastases from any primary cancer eligible for anti-PD-1. Stereotactic body RT (SBRT) is delivered at tumor-site specific doses per standard practice. Primary objective is to determine the NBTXR3\/SBRT\/anti-PD-1 recommended phase 2 dose in each cohort. Secondary objectives are anti-tumor response (objective response rate), safety, and feasibility of NBTXR3 injection.<\/p>\n

Results:<\/b> Nine pts have been treated, 3 HNSCC, 4 lung and 2 liver. HNSCC was the primary cancer in 2 pts in the lung and 1 pt in the liver cohort. 7\/9 pts were anti-PD-1 non-responders. Overall tumor regression was observed in 8\/9 pts. NBTXR3\/SBRT\/anti-PD-1 resulted in tumor regression in 6\/7 pts who had progressed on prior anti-PD-1. One anti-PD-1 na\u00efve HNSCC pt achieved a complete response lasting over a year in the injected lymph node. 2 SAEs related to anti-PD-1 and possibly related to NBTXR3 (G5 pneumonitis, G4 hyperglycemia) were observed in 1 anti-PD-1 na\u00efve HNSCC pt and considered DLTs. This pt also experienced 2 other SAEs (G4 diabetic ketoacidosis, G4 acute kidney injury) related to anti-PD-1. SBRT-related safety profile was as expected.<\/p>\n

Conclusions:<\/b> Safety data from this first-in-human phase I trial evaluating NBTXR3\/SBRT\/anti-PD-1 in pts with advanced cancers show NBTXR3 intratumoral injection is feasible and well-tolerated in HNSCC, lung, and liver metastases. NBTXR3\/SBRT\/anti-PD-1 demonstrated promising signs of efficacy and led to tumor regression in pts having progressed on prior anti-PD-1. These data support further development of NBTXR3\/SBRT in combination with anti-PD-1 as well as other ICIs.[\/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_row_inner][\/vc_column][\/vc_row]<\/p>\n<\/section>","protected":false},"excerpt":{"rendered":"

Immune checkpoint inhibitors (ICIs) have improved treatment outcomes in a variety of cancers; however the majority of patients (pts) exhibit resistance. Emerging evidence suggests radiation therapy (RT) can enhance response to ICIs by producing an immunomodulatory effect. NBTXR3, composed of functionalized hafnium oxide nanoparticles, is injected intratumorally and activated by RT. [\u2026]<\/p>\n","protected":false},"author":1,"featured_media":3011,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":[],"categories":[182,183,669,181,670,668],"tags":[197,455,463,545,342,542,200,203],"aioseo_notices":[],"_links":{"self":[{"href":"https:\/\/bibliography.nanobiotix.com\/fr\/wp-json\/wp\/v2\/posts\/3086"}],"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=3086"}],"version-history":[{"count":1,"href":"https:\/\/bibliography.nanobiotix.com\/fr\/wp-json\/wp\/v2\/posts\/3086\/revisions"}],"predecessor-version":[{"id":3088,"href":"https:\/\/bibliography.nanobiotix.com\/fr\/wp-json\/wp\/v2\/posts\/3086\/revisions\/3088"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/bibliography.nanobiotix.com\/fr\/wp-json\/wp\/v2\/media\/3011"}],"wp:attachment":[{"href":"https:\/\/bibliography.nanobiotix.com\/fr\/wp-json\/wp\/v2\/media?parent=3086"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/bibliography.nanobiotix.com\/fr\/wp-json\/wp\/v2\/categories?post=3086"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/bibliography.nanobiotix.com\/fr\/wp-json\/wp\/v2\/tags?post=3086"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}