NBTXR3 + Radiotherapy for Cancer

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new cancer treatment by injecting NBTXR3 (Hafnium Oxide nanoparticles) directly into tumors, followed by targeted radiation and a type of immune therapy. The goal is to determine if this approach is safe and effective for cancers like head and neck, lung, or liver cancer that have spread or cannot be surgically removed. Eligible participants include those who have tried other treatments, such as anti-PD-1 therapy, without success and have tumors that can be easily targeted and measured. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative 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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that NBTXR3, when combined with radiotherapy, has a safety profile similar to existing treatments like liver SBRT. However, 42-47% of patients experienced serious side effects, classified as grade 3 or higher. This indicates that while effective, it may also have significant side effects.

Research on nivolumab, an anti-PD-1 therapy, shows that serious side effects, such as pneumonia and fever, occur in at least 2% of patients. Nivolumab's approval for other conditions suggests that its safety profile is generally manageable.

Large trials have tested pembrolizumab, another anti-PD-1 therapy, revealing that 78.6% of patients experienced side effects, with 16.3% experiencing severe ones. Despite this, its common use indicates that its risks are often considered acceptable.

Weighing these potential side effects against the benefits is crucial when considering participation in a trial. Consulting with a healthcare provider to discuss these factors is always recommended. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for cancer, which typically involve systemic chemotherapy or conventional radiotherapy, this approach uses NBTXR3 activated by SABR, followed by anti-PD-1 monotherapy with nivolumab or pembrolizumab. NBTXR3 is a new type of nanoparticle that enhances the effects of radiotherapy directly at the tumor site, potentially increasing the precision and effectiveness of treatment. The combination with immune checkpoint inhibitors like nivolumab or pembrolizumab aims to boost the body's immune response against cancer cells. Researchers are excited because this dual approach could offer a more targeted and potentially more effective treatment option with fewer side effects.

What evidence suggests that this trial's treatments could be effective for cancer?

Research has shown that NBTXR3, when combined with radiotherapy, destroys cancer cells and controls tumor growth more effectively than radiotherapy alone. This treatment uses tiny particles to enhance the effects of radiation, leading to increased cancer cell death with minimal impact on healthy tissue. In this trial, participants will receive an intratumoral injection of NBTXR3 followed by SABR (stereotactic ablative radiotherapy).

Afterward, participants will receive anti-PD-1 monotherapy with either Nivolumab or Pembrolizumab. Nivolumab has demonstrated promising results in extending survival across various cancer types, with studies finding that some patients live more than 21 months, and it is effective even as a standalone treatment. Pembrolizumab, another treatment tested in this trial, has shown long-term success, with up to 22% of patients living at least five years in some studies. It is well-known for effectively treating different cancers, especially as a first-line treatment option. ^{1 2 3 4 6}

Who Is on the Research Team?

Pavel Tyan, MD

Principal Investigator

Nanobiotix

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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 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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8052129/

NBTXR3 Radiotherapy-Activated Functionalized Hafnium ... NBTXR3 activated by radiotherapy was also more effective in destroying cancer cells and in controlling tumor growth than radiotherapy alone.

2. sciencedirect.com sciencedirect.com/science/article/pii/S2452109425002246

Radioenhancing hafnium oxide nanoparticles (NBTXR3 ... NBTXR3, a novel radioenhancer, demonstrated enhanced radiotherapy efficacy with minimal toxicity in healthy tissue. We evaluated NBTXR3 ...

3. tandfonline.com tandfonline.com/doi/full/10.2217/nnm-2022-0186

A Phase Ib/II Trial of PEP503 (NBTXR3, Radioenhancer ... PEP503 (NBTXR3) nanoparticle injection with radiotherapy has increased cancer cell death compared with radiotherapy alone [Citation7–11]. Therefore, PEP503 ( ...

4. nanobiotix.com nanobiotix.com/wp-content/uploads/2023/10/8-A-phase-IbII-trial-of-PEP503-with-radiotherapy-and-chemotherapy-in-patients-with-rectal-cancer.pdf

A phase Ib/II trial of PEP503 (NBTXR3, radioenhancer) with ... PEP503 (NBTXR3) nanoparticle injection with radiotherapy has increased cancer cell death compared with radiotherapy alone [7–11]. Therefore, ...

5. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO.2021.39.3_suppl.66

A new radio-enhancer, PEP503 (NBTXR3), in combination ... Conclusions: Intra-tumor injection of PEP503/NBTXR3 with CCRT is feasible without additional toxicities for rectal cancer patients. The ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.e18041

PEP503 (NBTXR3), a radioenhancer, in combination with ... Conclusions: Adding PEP503, a radioenhancer, via a single intratumoral injection to weekly cisplatin-containing CCRT was feasible and safe for ...