NBTXR3 +/− Cetuximab for Head and Neck Cancer

Recruiting at 281 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Johnson & Johnson Enterprise Innovation Inc.

Disqualifiers: Nasopharynx carcinoma, Non-squamous histology, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 7 weeks

500 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called NBTXR3 for individuals with locally advanced head and neck cancer who cannot receive platinum-based chemotherapy. It tests the effectiveness of NBTXR3 when combined with radiation therapy, with or without cetuximab, a type of targeted therapy. The trial includes two groups: one receives NBTXR3 with radiation, and the other receives only radiation (with or without cetuximab). Suitable candidates have head and neck cancer treatable with radiation but cannot undergo platinum chemotherapy. As a Phase 3 trial, this treatment represents the final step before FDA approval, offering patients a promising opportunity to access potentially effective therapy.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Studies have shown that NBTXR3, when used with radiotherapy, is generally safe for patients. Research indicates that injecting this special enhancer directly into the tumor is well-tolerated. Previous studies reported no serious safety concerns. In fact, these studies suggest that NBTXR3 can enhance the effectiveness of radiotherapy in killing cancer cells and slowing tumor growth. While minor side effects may occur, past research considers the overall safety of NBTXR3 to be good. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for head and neck cancer, which typically include radiation therapy (RT) and the drug cetuximab, NBTXR3 is unique because it is a nanoparticle injected directly into the tumor or lymph nodes and activated by radiation. This method allows for a more targeted approach, potentially enhancing the effectiveness of the radiation therapy. Researchers are excited about NBTXR3 because it promises to boost the local control of tumors without increasing systemic side effects. This innovative approach could lead to better outcomes for patients with head and neck cancer by maximizing the impact of radiation where it's needed most.

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

Research has shown that NBTXR3, a treatment under study in this trial, can enhance the effectiveness of radiotherapy in destroying cancer cells and controlling tumor growth compared to radiotherapy alone. In studies on head and neck cancer, NBTXR3 has demonstrated potential in amplifying the effects of radiotherapy, possibly leading to new treatment options for patients. Early results suggest that NBTXR3 is well tolerated and effective in patients with recurring head and neck cancer. Overall, these studies offer hope that NBTXR3 could improve outcomes for those with challenging cases of head and neck cancer. Participants in this trial may receive NBTXR3 with radiotherapy, with or without Cetuximab, as part of the study's treatment arms. ^{1 2 5 6 7}

Who Is on the Research Team?

Johnson & Johnson Enterprise Innovation Inc Clinical trial

Principal Investigator

Johnson & Johnson Enterprise Innovation Inc.

Are You a Good Fit for This Trial?

This trial is for people aged 65 or older with a specific type of throat cancer (SCC) that hasn't been treated before. They must be able to handle radiation therapy, not have certain other health issues like severe allergies to cetuximab, HIV, active hepatitis B or C, heart problems, or lung disease. Women who are pregnant or nursing and those not using birth control can't join.

Inclusion Criteria

My cancer is confirmed as squamous cell carcinoma in specific areas of the head or neck.

I can undergo radiation therapy with the goal of curing my condition.

My cancer is classified as T3-T4 or T2 with significant lymph node involvement.

Exclusion Criteria

I do not have serious heart rhythm problems.

Subject participating in another clinical study at the time of signature of the informed consent form

My head or neck cancer has returned but I haven't had chemo or radiation for it.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment

Participants receive 70 Gy in 35 fractions over a 7 week period, with either RT alone or RT in combination with cetuximab

7 weeks

End of Treatment (EOT)

An EOT visit is performed 4 weeks after the completion of RT

4 weeks

Follow-up

Follow-up visits start at 12 weeks post-RT completion, continuing every 12 weeks for 2 years, then every 24 weeks thereafter until death or study end

48 months

What Are the Treatments Tested in This Trial?

Interventions

• Cetuximab
• NBTXR3

Trial Overview The study tests NBTXR3 combined with radiation therapy (RT), with or without the drug cetuximab. It's an open-label Phase 3 trial where patients are randomly assigned to one of two groups: one receiving NBTXR3/RT±cetuximab and the other receiving RT±cetuximab alone.

How Is the Trial Designed?

Group I: Arm A Experimental Treatment 3 Interventions

JNJ-90301900 (NBTXR3), as an intratumoral/intranodal injection, activated by investigator's choice of RT alone or RT in combination with cetuximab. JNJ-90301900 (NBTXR3) is given as a dose of 33% of the Gross Tumor Volume.

Group II: Arm B Active Control 2 Interventions

Investigator's choice of RT alone or RT in combination with cetuximab.

Who Is Running the Clinical Trial?

Johnson & Johnson Enterprise Innovation Inc.

Lead Sponsor

Trials

5

Recruited

910+

Nanobiotix

Lead Sponsor

Trials

7

Recruited

950+

Published Research Related to This Trial

Cetuximab alone slightly inhibited the growth of Hep-2 cells but did not induce cell death, indicating limited efficacy on its own.

When combined with cisplatin, cetuximab significantly enhanced the inhibition of cell growth and increased apoptosis, suggesting that its clinical effectiveness may be more related to its ability to boost the effects of other pro-apoptotic treatments rather than just inhibiting cell repopulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of the administration of epidermal growth factor receptor specific inhibitor cetuximab, alone and in combination with cisplatin, on proliferation and apoptosis of Hep-2 laryngeal cancer cells. Bussu, F., Pozzoli, G., Giglia, V., et al.[2019]

In a Phase III trial, adding cetuximab to radiotherapy for locoregionally advanced squamous cell carcinoma of the head and neck significantly improved median locoregional control from 14.9 to 24.4 months and overall survival from 29.3 to 49.0 months.

For patients with platinum-refractory recurrent or metastatic disease, cetuximab combined with platinum/5-fluorouracil showed improved survival, response rates (10-13%), and disease control (46-56%), along with better symptom management compared to platinum/5-fluorouracil alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab in the treatment of squamous cell carcinoma of the head and neck. Specenier, P., Vermorken, JB.[2019]

The phase I study involving 19 elderly or frail patients with advanced head and neck cancer showed that the radioenhancer nanoparticles, NBTXR3, had a good safety profile, with no dose-limiting toxicities or serious adverse events related to the treatment.

NBTXR3 was successfully injected intratumorally and remained localized during radiation therapy, with preliminary signs of antitumor activity observed, indicating its potential for further evaluation in this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I dose-escalation study of NBTXR3 activated by intensity-modulated radiation therapy in elderly patients with locally advanced squamous cell carcinoma of the oral cavity or oropharynx. Hoffmann, C., Calugaru, V., Borcoman, E., et al.[2021]

The combination of cetuximab (Cet) with the TPF chemotherapy regimen (docetaxel, cisplatin, and fluorouracil) significantly reduced tumor volume and improved histological responses in a mouse model of advanced head and neck cancer, indicating strong anti-tumor activity.

Adding bevacizumab (Bev) to the TPF-Cet combination did not provide additional benefits over the TPF-Cet treatment alone, suggesting that TPF-Cet is a highly effective option for managing advanced head and neck tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor activity of cetuximab associated with the taxotere-cisplatin-fluorouracil (TPF) combination on an orthotopic head and neck cancer model. Bozec, A., Sudaka, A., Etienne-Grimaldi, MC., et al.[2018]

The new chemotherapy regimen combining docetaxel, cisplatin, and cetuximab (B-CRT) for treating locally advanced head and neck squamous cell carcinoma resulted in severe neutropenia in 56% of patients, indicating significant safety concerns.

Due to the high incidence of adverse events, particularly neutropenia and leukopenia, the study was terminated early, and it remains unclear if B-CRT is as effective as the standard TPF-CRT regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of concurrent bio-chemoradiotherapy using docetaxel, cisplatin, and cetuximab for locally advanced head and neck squamous cell carcinoma. Nishimura, G., Taguchi, T., Takahashi, M., et al.[2018]

Conjugating cetuximab with CHX-A"-DTPA and radiolabeling it with (90)Yttrium does not change its ability to block cancer cell growth or its binding affinity to the EGFR, ensuring that its therapeutic function remains intact.

The combination of (90)Y-cetuximab with external-beam irradiation significantly enhances the inhibition of head and neck squamous cell carcinoma cell growth, suggesting a potential improvement in radiotherapy outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cellular and molecular properties of (90)Y-labeled cetuximab in combination with radiotherapy on human tumor cells in vitro. Saki, M., Toulany, M., Sihver, W., et al.[2021]

Monoclonal antibodies like cetuximab work by promoting receptor endocytosis and activating the immune system to reduce tumor growth in head and neck squamous cell carcinoma (HNSCC).

Different strategies for targeting EGFR, including tyrosine kinase inhibitors and antisense approaches, have unique mechanisms of action, which could lead to more effective treatments and better patient selection for EGFR inhibition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Investigational EGFR-targeted therapy in head and neck squamous cell carcinoma. Cassell, A., Grandis, JR.[2021]

Cetuximab is a monoclonal antibody that effectively inhibits the epidermal growth factor receptor (EGFR), which plays a crucial role in tumor growth and resistance to treatments like chemotherapy and radiotherapy.

Clinical data suggest that cetuximab not only has its own anticancer effects but may also enhance the effectiveness of chemotherapy and radiotherapy in patients with advanced head and neck cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of cetuximab in the treatment of squamous cell carcinoma of the head and neck. Merlano, M., Occelli, M.[2021]

Cetuximab, a monoclonal antibody targeting the EGFR, has been shown to improve survival rates when used alongside radiation therapy for patients with locally-advanced head and neck cancer, as demonstrated in a landmark study.

In recurrent and metastatic cases, cetuximab also enhances the effectiveness of chemotherapy, indicating its significant role in the treatment of squamous cell carcinoma of the head and neck, although further research is needed to optimize its use and identify the best patient candidates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of cetuximab in the management of head and neck cancers. Kabolizadeh, P., Kubicek, GJ., Heron, DE., et al.[2020]

Cetuximab is an effective treatment for squamous cell carcinoma of the head and neck, enhancing the effects of radiotherapy and improving response rates when combined with cisplatin chemotherapy, as indicated by a significant hazard ratio for progression of 0.78.

The most common side effect of cetuximab is an acneiform rash, which occurs in 70-80% of patients and may serve as a prognostic marker for treatment response and survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of cetuximab in the treatment of squamous cell cancer of the head and neck. Burtness, B.[2019]

In a meta-analysis of seven randomized controlled trials, cetuximab combined with radiotherapy resulted in significantly poorer overall survival and locoregional control compared to cisplatin combined with radiotherapy in patients with head and neck squamous cell carcinoma (HNSCC).

While cetuximab showed inferior efficacy, the overall incidence of severe adverse events was similar between the cetuximab and cisplatin treatment groups, indicating that cetuximab may not provide a safety advantage despite its reduced effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy plus cetuximab or cisplatin in head and neck squamous cell carcinoma: an updated systematic review and meta-analysis of randomized controlled trials. Li, Y., Yang, C., Gan, Y., et al.[2023]

Cetuximab, when combined with platinum-based chemotherapy, showed a higher overall response rate (34.2%) compared to platinum therapy alone (17.0%) in patients with recurrent/metastatic head and neck squamous cell carcinoma, indicating its potential to enhance treatment efficacy.

Despite the improved response rates, the aggregate analysis revealed no significant improvement in overall survival when comparing platinum-based therapy plus cetuximab to platinum therapy alone, suggesting that cetuximab should complement existing treatments rather than replace them until more conclusive data is available.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cetuximab therapy for head and neck squamous cell carcinoma: a systematic review of the data. Reeves, TD., Hill, EG., Armeson, KE., et al.[2018]

Citations

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

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

2. ir.nanobiotix.com ir.nanobiotix.com/news-releases/news-release-details/nanobiotix-announces-first-data-phase-1-study-evaluating-jnj

NANOBIOTIX Announces First Data From Phase 1 Study ... Radiotherapy-activated JNJ-1900 (NBTXR3) is being evaluated across multiple solid tumor indications as a single agent or combination therapy.

3. targetedonc.com targetedonc.com/view/nbtxr3-well-tolerated-in-r-m-hnscc-with-early-efficacy-signals

NBTXR3 Well Tolerated in R/M HNSCC, With Early Efficacy ... Innovative NBTXR3 shows promise in enhancing radiotherapy for recurrent head and neck cancer, potentially transforming treatment options for ...

4. 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.

5. asco.org asco.org/abstracts-presentations/ABSTRACT362356

Dose-finding of a phase 1b/2 trial. PEP503 nanoparticles plus RT has been tested in elderly HNSCC patients and has demonstrated a good safety profile. The phase 1b part of the study aimed to test ...

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

A Phase Ib/II Trial of PEP503 (NBTXR3, Radioenhancer ... This study reveals the protocol of a phase Ib/II study to investigate the safety profile, dose-limiting toxicity and antitumor activity of PEP503 (NBTXR3) ...

7. ir.nanobiotix.com ir.nanobiotix.com/news-releases/news-release-details/nanobiotix-announces-updates-jnj-1900-nbtxr3-clinical-program

NANOBIOTIX Announces Updates to JNJ-1900 (NBTXR3) ... Radiotherapy-activated JNJ-1900 (NBTXR3) is being evaluated across multiple solid tumor indications as a single agent or combination therapy.