2020 – Phase I study of NBTXR3 activated by radiotherapy in patients with advanced cancers treated with an anti-PD-1 therapy

nano-pub — Thu, 26 May 2022 11:39:15 +0000

Authors

Colette Shen, Jessica Frakes, Jared Weiss, Jimmy J. Caudell, Trevor G Hackman, Jason A. Akulian, Ghassan El-Haddad, Yun Hu, Robert Dixon, Alexander T. Pearson, Hampartsoum B. Barsoumian, Maria Angelica Cortez, Katherine LaRoque Jameson, Patricia Said, James William Welsh, Tanguy Y. Seiwert

University of North Carolina at Chapel Hill, Chapel Hill, NC; Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; University of North Carolina Hospitals, Chapel Hill, NC; H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; University of North Carolina, Chapel Hill, NC; Moffitt Cancer Center, Tampa, FL; MD Anderson, Houston, TX; University of North Carolina At Chapel Hill, Chapel Hill, NC; Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL; The University of Texas MD Anderson Cancer Center, Houston, TX; Vanderbilt Univ Medcl Ctr, Nashville, TN; Nanobiotix, Paris, France; University of Chicago, Chicago, IL

Summary

Background: Despite the past decade of transformative advances in immuno-oncology, the response rate to checkpoint inhibitors (ICIs) remains low (~15%). There is significant interest in developing strategies to overcome resistance to these treatments, thus increasing response rate. Emerging evidence suggests that radiation therapy (RT) could potentially augment the antitumor response to ICIs through synergic effect. However, RT dose and ultimate efficacy are limited by toxicity related to exposure of healthy tissues. NBTXR3 is a first-in-class radioenhancer administered by direct intratumoral injection, designed at the nanoscale to increase RT dose deposition within tumor cells and RT-dependent tumor cell killing, without increasing surrounding normal tissue toxicity. 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.

Method: This trial [NCT03589339] is a multicenter, open-label, phase I study to 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 gross tumor volume (GTV). 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. To date, three patients have been treated, one in cohort 1, two in cohort 2.

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2019 – ESMO IO – NBTXR3 with anti-PD-1

nano-pub — Tue, 25 Feb 2020 15:22:38 +0000

Authors

Colette Shen1, Katherine Jameson2, Jared Weiss1, Trevor Hackman1, Daniel Corum2, Jason A. Akulian1, Robert Dixon1, Alexander Pearson3, Jessica Frakes4, Patricia Said2, Hichem Miraoui2, Edwina Baskin-Bey2, Tanguy Seiwert5

1 – University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA
2 – Nanobiotix, Paris, France
3 – University of Chicago Medicine, Chicago, Illinois, USA
4 – Moffitt Cancer Center, Tampa, Florida, USA
5 – Johns Hopkins Medicine, Baltimore, Maryland, USA

Summary

Background: The majority of cancer patients are resistant to immune therapy; only around 15% respond to immune checkpoint inhibitors (ICI). Thus, strategies able to increase ICI response are of great interest. Recent work suggests radiotherapy (RT) can act as an immunomodulator to increase the proportion of ICI responders and improve clinical outcomes. However, RT dose and ultimate efficacy are limited by toxicity related to exposure of healthy tissues. NBTXR3 is a first-in-class radioenhancer administered by intratumoral injection, designed at the nanoscale to increase RT energy dose deposition within the tumor. The result is increased radiation-dependent tumor cell killing, without increasing radiation exposure of healthy tissues. Preclinical and early clinical data suggest NBTXR3 activated by RT can increase the 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 while also producing a systemic response sufficient to increase the proportion of ICI responders or convert ICI non-responders to responders.

Trial Design: NANORAY-1100 [NCT03589339] is a multicenter, open-label, phase 1 study to 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 from any primary cancer eligible for anti-PD-1, or (3) Liver metastases from any primary cancer eligible for anti-PD-1. Approximately two-thirds of each cohort will be composed of anti-PD-1 non-responders. NBTXR3 injection volume is based on a percentage of gross tumor volume (GTV) determined by central review. The primary objective is to determine R3/RT/PD-1 RP2D. Secondary objectives are to evaluate anti-tumor response (objective response rate; ORR) of R3/RT/PD-1, 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, mRNA and cytokine immune marker profiling.

The post 2019 – ESMO IO – NBTXR3 with anti-PD-1 first appeared on Nano Publications.

lung metastases | Nano Publications

2020 – Phase I study of NBTXR3 activated by radiotherapy in patients with advanced cancers treated with an anti-PD-1 therapy

Authors

Summary

2019 – ESMO IO – NBTXR3 with anti-PD-1

Authors

Summary