NT219 for Head and Neck Cancer

Recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Colorado, Denver

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Unknown origin cancer, Active HIV, others

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

Compensation: Varies

Number of Visits: 228

Duration: Until progression or unacceptable toxicity

29 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called NT219 for head and neck cancer that cannot be cured. The study tests NT219 in combination with two existing treatments, pembrolizumab and cetuximab, to evaluate their combined effectiveness. It targets individuals whose head and neck cancer has not responded well to other treatments. For those with recurrent or worsening head and neck cancer who are familiar with treatments like pembrolizumab or cetuximab, this trial may be suitable. As a Phase 1, Phase 2 trial, the research focuses on understanding how NT219 works in people and measuring its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, there are washout periods for certain treatments, like prior anti-cancer biologic agents, chemotherapy, and radiation therapy, which must be stopped a few weeks before starting the trial.

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

Research has shown that NT219, when combined with pembrolizumab, was safe in earlier studies. The most common side effects included infusion-related reactions (in 76% of cases) and nausea (in 35.3% of cases).

For those considering NT219 with cetuximab, studies have found it to be generally safe and well-tolerated. This combination also demonstrated some ability to fight tumors in patients with head and neck cancer.

Both combinations have been tested in patients with head and neck cancer and are manageable for most people. However, like any treatment, side effects can occur, so participants should discuss these with their doctors. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike standard treatments for head and neck cancer, which often rely on chemotherapy and radiation, NT219 offers a novel approach by targeting specific signaling pathways involved in cancer cell survival. Researchers are excited about NT219 because it works by inhibiting IRS and STAT3, which are proteins that help cancer cells resist treatment. This makes NT219 particularly promising when combined with pembrolizumab, a PD-1 inhibitor, for patients who haven't benefited from PD-1 inhibitors in the past. Additionally, NT219 combined with cetuximab is tailored for patients who have not responded to multiple treatments, potentially offering a new lifeline where standard therapies fall short.

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

This trial will evaluate NT219 combined with either pembrolizumab or cetuximab for head and neck cancer. Research has shown that using NT219 with pembrolizumab, which participants in Cohort 1 may receive, may help treat head and neck cancer. Although pembrolizumab alone has been successful, about 60% of patients still experience cancer progression. Adding NT219 might help by targeting pathways that could reduce cancer resistance to treatment.

In Cohort 2, participants will receive NT219 combined with cetuximab. Studies have found this combination to be safe and effective for patients with recurring or spreading head and neck cancer. It has demonstrated the ability to fight tumors and can even overcome resistance to cetuximab. Both combinations show promising results and could offer new hope for patients. ^{1 2 3 5 6}

Who Is on the Research Team?

Alice Weaver, MD, PhD

Principal Investigator

University of Colorado, Denver

Are You a Good Fit for This Trial?

Adults over 18 with incurable head and neck squamous cell carcinoma that's not caused by EBV can join. They should have recovered from previous cancer treatments, have measurable disease, and good organ/marrow function. Specific groups include those who've benefited from anti-PD-1 therapy or are new to it, as well as candidates for cetuximab after PD-1 inhibitors didn't work.

Inclusion Criteria

I can have biopsies on my cancer that's not being targeted by current treatments.

I have benefited from anti-PD-1 therapy for at least 6 months or achieved partial/complete response without disease progression.

I have recovered from major side effects of my last cancer treatment.

Exclusion Criteria

I have received an organ transplant.

My cancer is squamous type but its origin is unknown.

My cancer is linked to the Epstein-Barr virus.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive NT219 weekly plus pembrolizumab every 3 weeks or cetuximab weekly until progression, unacceptable toxicity, or decision to discontinue

Until progression or unacceptable toxicity

Weekly visits for NT219 and cetuximab, every 3 weeks for pembrolizumab

Follow-up

Participants are monitored for safety and effectiveness after treatment

9 weeks

Tumor assessments every 9 weeks

Dose-limiting Toxicity Assessment

Assessment of dose-limiting toxicities within the first 21-day cycle for NT219 plus pembrolizumab

3 weeks

What Are the Treatments Tested in This Trial?

Interventions

• NT219

Trial Overview The trial tests NT219 combined with pembrolizumab every three weeks or weekly cetuximab until the cancer progresses, side effects become too much, or the participant/investigator decides to stop. The goal is to see if this combo helps control the cancer better than current treatments.

How Is the Trial Designed?

Group I: Cohort 2 NT219 plus cetuximab Experimental Treatment 1 Intervention

Cohort 2 will enroll patients who had progression of disease without clinical benefit from PD-1 inhibition or have received 2 or more lines of therapy and are good candidates for cetuximab. Patients will be treated with NT219 100mg/kg once weekly plus cetuximab given as an initial loading dose of 400 mg/m2 followed by maintenance dosing of 250 mg/m2 once weekly.

Group II: Cohort 1 NT219 plus pembrolizumab Experimental Treatment 1 Intervention

Cohort 1 will enroll patients who have not received PD-1 inhibition in the relapsed/metastatic setting or have received and derived significant clinical benefit from PD-1 inhibition as their first line of therapy. Patients will be treated with NT219 100 mg/kg once weekly plus pembrolizumab 200 mg once every three weeks. The first 6 patients will be required to clear a DLT window of 21 days as an abbreviated safety lead-in.

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

Purple Biotech Ltd.

Industry Sponsor

Citations

1. esmoopen.com esmoopen.com/article/S2059-7029(24)00123-6/fulltext

27O Interim results of a phase I/II trial of NT219 in ... Conclusions. NT219 in combination with cetuximab is well tolerated and exhibits anti-tumor activity in R/M SCCHN pts at dose levels equivalent to animal model ...

2. onclive.com onclive.com/view/nt219-plus-cetuximab-elicits-responses-demonstrates-tolerability-in-recurrent-or-metastatic-hnscc

NT219 Plus Cetuximab Elicits Responses, Demonstrates ... Second-line treatment with NT219 alone and in combination with cetuximab demonstrated safety and tolerability, and the combination produced confirmed partial ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06919666

Study Details | NCT06919666 | NT219 Combined With ... NT219 also synergized with cetuximab in vitro and reversed cetuximab resistance in a head and neck cancer xenograft platform.

4. clin.larvol.com clin.larvol.com/trial-detail/NCT04474470

A Study to Evaluate NT219 Alone and in Combination with ... "The new data demonstrates IRS2-amplified colorectal cancer (CRC) cells upregulate β-catenin expression, and treatment with NT219 significantly decreased the β ...

5. onclive.com onclive.com/view/nt219-plus-cetuximab-demonstrates-efficacy-tolerability-in-scchn

NT219 Plus Cetuximab Demonstrates Efficacy, Tolerability ... NT219 in combination with cetuximab was safe and effective in patients with recurrent/metastatic squamous cell carcinoma of the head and neck.

6. targetedonc.com targetedonc.com/view/nt219-delivers-safety-responses-in-scchn

NT219 Delivers Safety Responses in SCCHN In a phase 1/2 trial of NT219 with cetuximab in patients with squamous cell carcinoma of the head and neck, safety and tolerability responses were encouraging.