NBTXR3 + Radiotherapy for Cancer

Recruiting at 18 trial locations

Overseen By Romain Gineste, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Nanobiotix

Must be taking: Anti-PD-1 therapy

Must not be taking: Checkpoint inhibitors, Live vaccines

Disqualifiers: Autoimmune disease, HIV, Hepatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

Duration: 4 weeks

145 Participants Needed

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. ^{1 2 3 4 5}

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. ^{1 2 5 6 7}

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. ^{5 6 7 8 9}

Research Team

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.

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.

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 Overview The 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

Group I: NBTXR3 activated by SABR followed by anti-PD-1 monotherapy Experimental Treatment 4 Interventions

Intratumoral injection of NBTXR3 followed by SABR followed by monotherapy with nivolumab or pembrolizumab

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

The combination of NBTXR3 nanoparticles with immunoradiotherapy (anti-PD1 and anti-CTLA4) significantly enhanced antitumor immune responses and reduced immune suppression in a mouse model of metastatic lung cancer, leading to the eradication of both primary and secondary tumors.

This treatment approach resulted in a 75% survival rate among the mice, with survivors showing a long-lasting antitumor memory immune response, suggesting potential for effective clinical applications in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NBTXR3 improves the efficacy of immunoradiotherapy combining nonfucosylated anti-CTLA4 in an anti-PD1 resistant lung cancer model. Hu, Y., Paris, S., Bertolet, G., et al.[2022]

Nivolumab and pembrolizumab are FDA-approved monoclonal antibodies that target PD-1, helping to enhance T cell activity against cancer by blocking the PD-1/PD-L1 interaction, which allows cancer cells to escape immune detection.

Both drugs have shown efficacy across multiple cancer types, including melanoma and non-small cell lung cancer, and are considered interchangeable options for treating these conditions, which may help manage the rising costs of cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nivolumab and pembrolizumab: Monoclonal antibodies against programmed cell death-1 (PD-1) that are interchangeable. Prasad, V., Kaestner, V.[2022]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

In a meta-analysis of 15 studies involving cancer patients treated with either nivolumab or pembrolizumab, nivolumab was associated with a higher overall incidence of cardiotoxicity (55.7%) compared to pembrolizumab (27.31%), although this difference was not statistically significant.

However, when looking specifically at myocarditis, pembrolizumab showed a significant increase in cardiotoxicity risk, suggesting that while nivolumab may be more commonly reported for general cardiotoxicity, pembrolizumab poses a greater risk for this specific heart condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative cardiotoxicity risk of pembrolizumab versus nivolumab in cancer patients undergoing immune checkpoint inhibitor therapy: A meta-analysis. Ndjana Lessomo, FY., Wang, Z., Mukuka, C.[2023]

In a study of platinum-sensitive recurrent or metastatic head and neck squamous cell carcinomas involving 36 patients, both nivolumab and pembrolizumab showed effectiveness, with median overall survival of 16.9 months for nivolumab and 19.2 months for pembrolizumab, indicating similar efficacy between the two treatments.

The median progression-free survival was 4.8 months for nivolumab and 9.3 months for pembrolizumab, with objective response rates of 38% and 47%, respectively, suggesting that both drugs are viable options for treatment in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Nivolumab and Pembrolizumab in Platinum-sensitive Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma. Yamashita, G., Okamoto, I., Ito, T., et al.[2023]

In a phase II study involving 29 patients with locally advanced head and neck squamous cell carcinoma who were ineligible for cisplatin, the combination of pembrolizumab and radiotherapy showed promising efficacy, with a 24-month progression-free survival rate of 71%.

The treatment was generally well-tolerated, although a significant number of patients experienced grade 3/4 lymphopenia (58.6%), indicating the need for monitoring immune cell changes during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent Definitive Immunoradiotherapy for Patients with Stage III-IV Head and Neck Cancer and Cisplatin Contraindication. Weiss, J., Sheth, S., Deal, AM., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Hafnium oxide nanoparticles: toward an in vitro predictive biological effect? [2021]

2. Ireland pubmed.ncbi.nlm.nih.gov

NBTXR3, a first-in-class radioenhancer for pancreatic ductal adenocarcinoma: Report of first patient experience. [2023]

3. England pubmed.ncbi.nlm.nih.gov

A radioenhancing nanoparticle mediated immunoradiation improves survival and generates long-term antitumor immune memory in an anti-PD1-resistant murine lung cancer model. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

NBTXR3 improves the efficacy of immunoradiotherapy combining nonfucosylated anti-CTLA4 in an anti-PD1 resistant lung cancer model. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Nivolumab and pembrolizumab: Monoclonal antibodies against programmed cell death-1 (PD-1) that are interchangeable. [2022]

6. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Comparative cardiotoxicity risk of pembrolizumab versus nivolumab in cancer patients undergoing immune checkpoint inhibitor therapy: A meta-analysis. [2023]

8. Greece pubmed.ncbi.nlm.nih.gov

Efficacy of Nivolumab and Pembrolizumab in Platinum-sensitive Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Concurrent Definitive Immunoradiotherapy for Patients with Stage III-IV Head and Neck Cancer and Cisplatin Contraindication. [2023]