145 Participants Needed

NBTXR3 + Radiotherapy for Cancer

Recruiting at 18 trial locations
KJ
RC
PT
RG
Overseen ByRomain Gineste, PhD
Age: 18+
Sex: Any
Trial Phase: Phase 1
Sponsor: Nanobiotix
Must be taking: Anti-PD-1 therapy
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

What is the purpose of this trial?

The 1100 study is an open-label, Phase I, dose escalation and expansion prospective clinical study to assess the safety of intratumoral injection of NBTXR3 activated by radiotherapy in combination with anti-PD-1 therapy.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you must not have received certain cancer treatments or vaccines recently, and you should discuss your specific medications with the trial team.

What data supports the effectiveness of the treatment NBTXR3 + Radiotherapy for Cancer?

Research shows that NBTXR3, when combined with radiotherapy, has shown clinical activity in various cancers like soft tissue sarcoma and head and neck cancer. Additionally, in animal studies, NBTXR3 combined with immunotherapy improved survival and created long-term immune memory against tumors.12345

Is NBTXR3 + Radiotherapy safe for humans?

NBTXR3, a type of hafnium oxide nanoparticle, has been used in clinical studies for various cancers, including pancreatic cancer, and has shown clinical activity. However, delivering radiation safely remains challenging due to potential toxicities in surrounding normal tissues. Pembrolizumab and nivolumab, which are sometimes used in combination with NBTXR3, have been associated with cardiac-related toxicities, so monitoring for heart-related side effects is important.12567

What makes the NBTXR3 + Radiotherapy treatment unique for cancer?

The NBTXR3 + Radiotherapy treatment is unique because it combines hafnium oxide nanoparticles (NBTXR3) with radiotherapy to enhance the effectiveness of the radiation, while also using immune checkpoint inhibitors like nivolumab and pembrolizumab to boost the body's immune response against cancer cells. This combination aims to improve treatment outcomes by both directly targeting the tumor and enhancing the immune system's ability to fight cancer.56789

Research Team

PT

Pavel Tyan, MD

Principal Investigator

Nanobiotix

Eligibility Criteria

This trial is for adults with advanced cancers like lung, kidney, bladder, skin cancer and more who have a life expectancy over 12 weeks. They must be able to receive radiotherapy and not have had certain treatments recently or suffer from conditions like severe heart failure or active infections.

Inclusion Criteria

I have never received anti-PD-1 therapy.
My cancer diagnosis was confirmed by a biopsy and is recommended for anti-PD-1 therapy.
My cancer has spread to a part of my lung that hasn't been treated with radiation.
See 17 more

Exclusion Criteria

My head or neck cancer has come back in the same area and has caused an open sore.
Any condition for which participation would not be in the best interest of the participant
I had severe side effects from previous anti-PD-1 cancer therapy, stopping further use.
See 13 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single intratumoral injection of NBTXR3 activated by radiotherapy followed by anti-PD-1 therapy

4 weeks
End of treatment visit 4 weeks after last radiotherapy fraction

Follow-up

Participants are monitored for long-term safety and efficacy

24 months

Treatment Details

Interventions

  • NBTXR3
  • Nivolumab
  • Pembrolizumab
Trial OverviewThe study tests NBTXR3 injected into tumors activated by radiotherapy alongside anti-PD-1 therapy (Pembrolizumab or Nivolumab). It's an open-label Phase I trial meaning everyone gets the treatment and doctors know what they're giving.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: NBTXR3 activated by SABR followed by anti-PD-1 monotherapyExperimental Treatment4 Interventions
Intratumoral injection of NBTXR3 followed by SABR followed by monotherapy with nivolumab or pembrolizumab

Find a Clinic Near You

Who Is Running the Clinical Trial?

Nanobiotix

Lead Sponsor

Trials
7
Recruited
950+

Findings from Research

NBTXR3 nanoparticles can be effectively taken up by various human cancer cell lines, with their uptake and clustering in cells depending on the concentration and type of cancer cells, indicating potential for targeted cancer therapy.
The study suggests that the radioenhancement effect of NBTXR3 nanoparticles can be predicted based on the concentration of nanoparticles and the radiation dose, which could help optimize treatment strategies for different types of cancer.
Hafnium oxide nanoparticles: toward an in vitro predictive biological effect?Marill, J., Anesary, NM., Zhang, P., et al.[2021]
The first patient with unresectable pancreatic ductal adenocarcinoma (PDAC) treated with NBTXR3 showed no acute adverse events, indicating a promising safety profile for this novel radioenhancer when combined with radiation therapy.
Local endoscopic delivery of NBTXR3 followed by intensity-modulated radiation therapy (IMRT) demonstrated feasibility, with the treatment maintaining tumor stability and no treatment-related toxicity observed during follow-up.
NBTXR3, a first-in-class radioenhancer for pancreatic ductal adenocarcinoma: Report of first patient experience.Bagley, AF., Ludmir, EB., Maitra, A., et al.[2023]
The combination of NBTXR3, high-dose radiation, low-dose radiation, and immune checkpoint inhibitors significantly improved survival rates in a mouse model of anti-PD1-resistant metastatic lung cancer, increasing survival from 0% to 50%.
This treatment enhanced the immune response by increasing CD8 T-cell infiltration and reducing regulatory T cells in the tumors, suggesting that NBTXR3 may help overcome resistance to anti-PD1 therapy by promoting a stronger antitumor immune response.
A radioenhancing nanoparticle mediated immunoradiation improves survival and generates long-term antitumor immune memory in an anti-PD1-resistant murine lung cancer model.Hu, Y., Paris, S., Barsoumian, H., et al.[2022]

References

Hafnium oxide nanoparticles: toward an in vitro predictive biological effect? [2021]
NBTXR3, a first-in-class radioenhancer for pancreatic ductal adenocarcinoma: Report of first patient experience. [2023]
A radioenhancing nanoparticle mediated immunoradiation improves survival and generates long-term antitumor immune memory in an anti-PD1-resistant murine lung cancer model. [2022]
NBTXR3 improves the efficacy of immunoradiotherapy combining nonfucosylated anti-CTLA4 in an anti-PD1 resistant lung cancer model. [2022]
Nivolumab and pembrolizumab: Monoclonal antibodies against programmed cell death-1 (PD-1) that are interchangeable. [2022]
Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]
Comparative cardiotoxicity risk of pembrolizumab versus nivolumab in cancer patients undergoing immune checkpoint inhibitor therapy: A meta-analysis. [2023]
Efficacy of Nivolumab and Pembrolizumab in Platinum-sensitive Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma. [2023]
Concurrent Definitive Immunoradiotherapy for Patients with Stage III-IV Head and Neck Cancer and Cisplatin Contraindication. [2023]