{"id":3089,"date":"2022-06-06T08:48:56","date_gmt":"2022-06-06T07:48:56","guid":{"rendered":"https:\/\/bibliography.nanobiotix.com\/?p=3089"},"modified":"2022-06-06T08:49:32","modified_gmt":"2022-06-06T07:49:32","slug":"2021-nbtxr3-activated-by-radiotherapy-in-combination-with-nivolumab-or-pembrolizumab-in-patients-with-advanced-cancers-a-phase-i-trial","status":"publish","type":"post","link":"https:\/\/bibliography.nanobiotix.com\/fr\/2021-nbtxr3-activated-by-radiotherapy-in-combination-with-nivolumab-or-pembrolizumab-in-patients-with-advanced-cancers-a-phase-i-trial\/","title":{"rendered":"2021 \u2013 NBTXR3 Activated by Radiotherapy in Combination With Nivolumab or Pembrolizumab in Patients With Advanced Cancers: A 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]Colette Shen1<\/span>, Jessica Frakes2<\/span>, Jiaxin Niu3<\/span>, Jared Weiss1<\/span>, Jimmy Caudell2<\/span>, Katherine Jameson4<\/span>, Patricia Said4<\/span>, Tanguy Seiwert5<\/span>
\n
\n1 \u2013 University of North Carolina School of Medicine;
\n2 \u2013 Moffitt Cancer Center;
\n3 \u2013 Banner MD Anderson Cancer Center;
\n4 \u2013 Nanobiotix;
\n5 \u2013 Johns Hopkins Medicine
\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\/Objective(s):<\/b> Immune checkpoint inhibitors (ICIs) have led to improved treatment outcomes in a variety of cancers; however, the majority of patients exhibit resistance to ICIs. Overcoming this resistance is a major challenge in immune-oncology. Radiation therapy (RT) has emerged as a promising combination with ICIs since it may act synergistically with ICIs by producing an immunomodulatory effect. NBTXR3, composed of functionalized hafnium oxide nanoparticles, is injected intratumorally and activated by RT. NBTXR3 increases RT energy deposit 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\/Methods:<\/b> This multicenter, open-label, phase I trial [NCT03589339] is evaluating NBTXR3\/RT\/anti-PD-1 in 3 cohorts: (1) Locoregional recurrent or recurrent and metastatic head and neck squamous cell carcinoma (HNSCC) amenable to HN re-irradiation and (2) lung or (3) liver metastases from any primary cancer eligible for anti-PD-1. Stereotactic body RT (SBRT) is delivered at tumor-site selective doses per standard practice. The primary objective is to determine the NBTXR3\/RT\/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 patients have been treated: 3 HNSCC, 4 lung, 2 liver. Overall tumor regression was observed in 8\/9 patients of which 7 were anti-PD-1 non-responders. A complete response lasting over 1 year was observed in the injected lymph node in 1 anti-PD-1 na\u00efve patient. 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 patient and considered DLTs. This patient also experienced 2 other G4 SAEs related to anti-PD-1 (diabetic ketoacidosis, acute kidney injury). SBRT-related safety profile was as expected. Updated safety and efficacy results with additional patients and longer follow-up will be presented.<\/p>\n

Conclusion:<\/b> Safety data from this first-in-human phase I trial evaluating NBTXR3\/RT\/anti-PD-1 in patients with advanced cancers, show NBTXR3 intratumoral injection is feasible and well-tolerated in HNSCC, lung, and liver. NBTXR3\/RT\/anti-PD-1 demonstrated promising signs of efficacy and led to tumor regression in patients having progressed on prior anti-PD-1. These data support further development of NBTXR3 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 led to improved treatment outcomes in a variety of cancers; however, the majority of patients exhibit resistance to ICIs. Overcoming this resistance is a major challenge in immune-oncology. Radiation therapy (RT) has emerged as a promising combination with ICIs since it may act synergistically with ICIs by producing an immunomodulatory effect. [\u2026]<\/p>\n","protected":false},"author":1,"featured_media":2879,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":[],"categories":[182,183,669,670,668],"tags":[197,411,455,545,342,542,200,203],"aioseo_notices":[],"_links":{"self":[{"href":"https:\/\/bibliography.nanobiotix.com\/fr\/wp-json\/wp\/v2\/posts\/3089"}],"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=3089"}],"version-history":[{"count":1,"href":"https:\/\/bibliography.nanobiotix.com\/fr\/wp-json\/wp\/v2\/posts\/3089\/revisions"}],"predecessor-version":[{"id":3091,"href":"https:\/\/bibliography.nanobiotix.com\/fr\/wp-json\/wp\/v2\/posts\/3089\/revisions\/3091"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/bibliography.nanobiotix.com\/fr\/wp-json\/wp\/v2\/media\/2879"}],"wp:attachment":[{"href":"https:\/\/bibliography.nanobiotix.com\/fr\/wp-json\/wp\/v2\/media?parent=3089"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/bibliography.nanobiotix.com\/fr\/wp-json\/wp\/v2\/categories?post=3089"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/bibliography.nanobiotix.com\/fr\/wp-json\/wp\/v2\/tags?post=3089"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}