On November 10, 2020 NANOBIOTIX (Paris:NANO) (Euronext: NANO – ISIN: FR0011341205 – the "Company"), a clinical-stage nanomedicine company pioneering new approaches to the treatment of cancer, reported positive first clinical results from a phase I study evaluating potentially first-in-class NBTXR3 activated by radiation therapy in combination with pembrolizumab or nivolumab (anti-PD-1 checkpoint inhibitors) for the treatment of patients with advanced cancers (Press release, Nanobiotix, NOV 10, 2020, View Source [SID1234570547]). The results were presented at The Society for the Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 35th Anniversary Annual Meeting.
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Addressing Unmet Needs in Cancer Immunotherapy
Cancer immunotherapies such as immune checkpoint inhibitors (ICIs) have shown promising clinical outcomes over the past two decades; and they are often used for patients with advanced cancers once other therapies have reached the end of their effectiveness. Additionally, the vast majority of patients only receive a temporary benefit or no benefit from ICIs, as they either develop resistance to the treatment during the course of therapy or are non-responsive to the treatment altogether (only 15%-20% of patients respond, according to published data). Taken together, these barriers present a significant unmet need to improve the efficacy ICIs and expand their potentially curative benefits to more patients with advanced cancers.
Combining ICIs with radiation therapy is emerging as a valuable strategy to "prime" an immune response and thereby increase the response rate, however the efficacy of radiation therapy is limited by toxicities related to the exposure of healthy tissues.
NBTXR3 is injected one time, directly into solid tumors. The product candidate is designed to increase the energy deposit from radiation therapy within the target tumor and subsequently increase the tumor-killing effect without increasing toxicity in surrounding healthy tissue. Pre-clinical and clinical data also suggest that NBTXR3 activated by radiation therapy can prime the immune system, creating an anti-tumor immune response that produces both local and systemic effects.
A Phase I Study of Intratumoral NBTXR3 in Combination with anti-PD-1 in Patients with Advanced Cancers
Colette Shen, Jessica Frakes, Jiaxin Niu, Jared Weiss, Jimmy Caudell, Katherine Jameson, Patricia Said, Tanguy Seiwert
Abstract ID: 410
Study 1100 is a multicenter, open-label, non-randomized, phase I dose escalation with dose expansion study evaluating NBTXR3 activated by radiation therapy in combination with anti-PD-1 (pembrolizumab or nivolumab) in three (3) cohorts of patients with advanced cancers: (i) inoperable locoregional recurrent or recurrent/metastatic head and neck cancer; (ii) lung metastasis; (iii) liver metastasis. The study is being administered across ten (10) sites in the United States.
The primary endpoint of the trial is recommended phase II dose (RP2D); the secondary endpoints are objective response rate (ORR), safety and feasibility, and body-kinetics; and the exploratory endpoints are survival outcomes, duration of response, and biomarkers of response.
First Results
To date, first results show that twenty AEs related to NBTXR3 or injection procedure (80% Grade 1-2) were reported in four patients (two each in the head and neck cancer and liver metastasis cohorts). One patient in the head and neck cancer cohort experienced 4 SAEs related to anti-PD-1 (nivolumab) of which two were also reported as possibly related to NBTXR3 (Grade 4 hyperglycemia and Grade 5 pneumonitis) and were considered dose-limiting toxicities. Pneumonitis is a known adverse event associated with nivolumab. There were no NBTXR3- or injection-related AEs, nor treatment-related SAEs in any of the patients treated in the lung metastasis cohort.
Regarding efficacy and generation of immune response linked to NBTXR3, tumor regression was observed in eight of nine patients including six of seven prior anti-PD-1 non-responders. Three out of seven patients who exhibited prior resistance to anti-PD-1 showed an overall partial response. Four of the anti-PD-1 non-responders also had multiple lesions, and three of those four experienced tumor regression in local and/or distant, non-injected lesions. One patient with prior resistance to anti-PD-1 experienced delayed tumor regression, which is an additional sign that an immune response may have been aided by NBTXR3 activated by radiation therapy.
Next Steps in Immunotherapy
Given the major opportunity to significantly improve treatment outcomes for patients by increasing the proportion of patients that respond to ICIs and positive early signs that potentially first-in-class NBTXR3 activated by radiation therapy could provide this benefit, Nanobiotix is preparing to accelerate development in immunotherapy. Recruitment in Study 1100 remains ongoing and the next update from the study is expected in the second quarter of 2021.
Nanobiotix will conduct a web conference to discuss the results in detail at 8:00AM Eastern Standard Time, 2PM Central European Time, on Friday, November 13th 2020. The web conference will include presentations from Colette Shen, M.D., Ph.D., and Jared Weiss, M.D.
Access the webcast: here
About NBTXR3
NBTXR3 is a novel, potentially first-in-class radioenhancer composed of functionalized hafnium oxide nanoparticles that is administered via one-time intra-tumoral injection and activated by radiation therapy. The primary mode of action (MoA) of NBTXR3 is designed to generate increased cellular destruction when activated by radiation therapy without increasing damage to healthy tissues. Subsequently, this cellular destruction also triggers an adaptive immune response.
NBTXR3 is being evaluated in locally advanced head and neck squamous cell carcinoma (HNSCC) of the oral cavity or oropharynx in elderly patients unable to receive chemotherapy or cetuximab with limited therapeutic options. Promising results have been observed in the phase I trial regarding local control. In the United States, the Company has started the regulatory process to commence a phase III clinical trial in locally advanced head and neck cancers. In February 2020, the United States Food and Drug Administration granted the regulatory Fast Track designation for the investigation of NBTXR3 activated by radiation therapy, with or without cetuximab, for the treatment of patients with locally advanced head and neck squamous cell cancer who are not eligible for platinum-based chemotherapy.
Nanobiotix is also running an Immuno-Oncology development program. The Company has launched a Phase I clinical trial of NBTXR3 activated by radiotherapy in combination with anti-PD-1 checkpoint inhibitors in locoregional recurrent (LRR) or recurrent and metastatic (R/M) HNSCC amenable to re-irradiation of the HN and lung or liver metastases (mets) from any primary cancer eligible for anti-PD-1 therapy.
Other ongoing NBTXR3 trials are treating patients with hepatocellular carcinoma (HCC) or liver metastases, locally advanced or unresectable rectal cancer in combination with chemotherapy, head and neck cancer in combination with concurrent chemotherapy, and pancreatic cancer. The Company is also engaged in a broad, comprehensive clinical research collaboration with The University of Texas MD Anderson Cancer Center to further expand the NBTXR3 development program.