{"id":1807,"date":"2019-06-04T07:31:29","date_gmt":"2019-06-04T06:31:29","guid":{"rendered":"https:\/\/bibliography.nanobiotix.com\/2019-ahns-phase-i-ii-nbtxr3-in-combination-with-anti-pd-1\/"},"modified":"2022-05-24T16:34:41","modified_gmt":"2022-05-24T15:34:41","slug":"2019-ahns-phase-i-ii-nbtxr3-in-combination-with-anti-pd-1","status":"publish","type":"post","link":"https:\/\/bibliography.nanobiotix.com\/fr\/2019-ahns-phase-i-ii-nbtxr3-in-combination-with-anti-pd-1\/","title":{"rendered":"2019 \u2013 AHNS \u2013 Phase I\/II 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\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]J. Welsh1<\/span>, T. Y. Seiwert2<\/span>, C. Le Tourneau3<\/span>, C. C. Foster2<\/span>, Y. Hu1, V. Calugaru3<\/span>, S. Bonvalot3<\/span>
\n
\n1 \u2013 MD Anderson Cancer Center, Houston, USA
\n2 \u2013 The University of Chicago Medicine, Chicago, USA
\n3 \u2013 Institut Curie, Paris, France
\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″]Hafnium oxide nanoparticles (NBTXR3) activated by radiotherapy (RT) increase radiation dose deposit within cancer cells compared to RT alone. There are currently 7 clinical trials underway to evaluate NBTRX3 activated by RT, including a phase I\/II study in elderly frail patients with locally advanced head and neck squamous cell carcinoma (HNSCC) [NCT01946867]. To date, no dose limiting toxicities (DLTs) have been observed. Studies in animals showed that NBTXR3 + RT can induce an immunogenic cell death-mediated abscopal effect which was not observed with RT alone. Furthermore, the immune cell infiltration profiles pre-treatment (biopsy) vs post-treatment (tumor resection) in patients with locally advanced Soft Tissue Sarcoma were modified in patients who received NBTXR3 + RT, compared to RT alone, as measured by immunohistochemistry. These results have led us to investigate the safety and systemic effect of NBTXR3 activated by stereotactic ablative radiotherapy (SABR) in combination with anti-PD-1 antibody in patients with more advanced disease: locoregionally recurrent or metastatic (to lung or liver) HNSCC, as well as in metastatic non-small cell lung cancer (NSCLC) and liver metastasis patients [NCT03589339].<\/p>\n

Recent clinical studies have demonstrated the efficacy of anti-PD-1 in recurrent\/metastatic HNSCC and metastatic NSCLC patients. However, only a subset of these patients benefits from this treatment, while most patients with recurrent\/metastatic HNSCC and metastatic NSCLC demonstrate innate (primary) resistance to checkpoint inhibition and do not respond to initial therapy. There is thus an important unmet medical need of a curative treatment for this checkpoint inhibition-resistant population. We hypothesize that intra-tumoral\/intralesional injection of NBXTR3 in the primary tumor or in one of the liver or lung metastases, followed by SABR may be a powerful mechanism to convert the local immune microenvironment to a \u201chot\u201d phenotype and thus help to overcome resistance to immune checkpoint inhibition.<\/p>\n

We have therefore designed an open label phase I\/II, non-randomized clinical study of NBTXR3 activated by SABR in combination with PD-1 blockade in patients with recurrent or metastatic HNSCC, metastatic NSCLC , or liver metastasis*. The phase I primary objective is to determine the maximum tolerated dose(s), the early DLTs and the recommended dose(s) of NBTXR3. The Phase II primary objectives are Complete Response Rate of target lesion\/s by RECIST v1.1 for the locoregional recurrent group, Objective Response Rate by RECIST v1.1 for the metastatic group, and safety and tolerability of SABR activated NBTXR3 in combination with anti-PD-1 at the recommended dose(s) in both groups.<\/p>\n

The mode of action of first-in-class NBTXR3 has already been demonstrated in a phase II\/III randomized trial in locally advanced soft tissue sarcoma patients. NBTXR3 activated by RT met both primary and main secondary endpoints and demonstrated a significant superiority in terms of clinical benefits compared to RT alone [NCT02379845]. The combination of NBTXR3 activated by SABR and PD-1 inhibition may therefore be able to improve patient response in advanced HNSCC and NSCLC.<\/p>\n

*Metastatic patients must have received an approved anti-PD1 with SD for at least for 12 weeks or with confirmed PD at 12 weeks.[\/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":"

Preoperative radiotherapy (RT) is an option for a subset of patients with locally advanced primary or relapsed tumors. Yet, its impact on efficacy in terms of pathological response is limited, highlighting the need for novel multimodal therapies aimed at local control with low toxicity. NBTXR3 is made of hafnium oxide nanoparticles which, injected intratumorally (IT) and activated by ionizing radiation, yield a tumor-localized high energy deposit and increase cell death compared to the same dose of RT alone. [\u2026]<\/p>\n","protected":false},"author":1,"featured_media":1802,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":[],"categories":[182,183,669,670,668],"tags":[539,540,196,541,465,545,342,542,200,503,543],"aioseo_notices":[],"_links":{"self":[{"href":"https:\/\/bibliography.nanobiotix.com\/fr\/wp-json\/wp\/v2\/posts\/1807"}],"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=1807"}],"version-history":[{"count":1,"href":"https:\/\/bibliography.nanobiotix.com\/fr\/wp-json\/wp\/v2\/posts\/1807\/revisions"}],"predecessor-version":[{"id":1808,"href":"https:\/\/bibliography.nanobiotix.com\/fr\/wp-json\/wp\/v2\/posts\/1807\/revisions\/1808"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/bibliography.nanobiotix.com\/fr\/wp-json\/wp\/v2\/media\/1802"}],"wp:attachment":[{"href":"https:\/\/bibliography.nanobiotix.com\/fr\/wp-json\/wp\/v2\/media?parent=1807"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/bibliography.nanobiotix.com\/fr\/wp-json\/wp\/v2\/categories?post=1807"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/bibliography.nanobiotix.com\/fr\/wp-json\/wp\/v2\/tags?post=1807"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}