Head and Neck CancerPhase 1/2NCT06919666
NT219 Combined With Standard of Care Biologic Therapy in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma
A Phase 1/2 study testing NT219 in people with Head and Neck Cancer and Head and Neck Squamous Cell Carcinoma, run by University of Colorado, Denver at 2 sites in United States.
Trial summary
Fixed dose NT219 weekly plus pembrolizumab every 3 weeks or cetuximab weekly to be continued until progression, unacceptable toxicity, or investigator or participant decision. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma
- What is being tested?
- NT219
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 2 sitesUnited States
- Study dates
- 12 Jun 2025to Feb 2031
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 and over.
- ECOG PS 0-2.
- Incurable head and neck squamous cell carcinoma of mucosal origin (oral cavity, tongue, oropharynx, pharynx, larynx, sinonasal and non-EBV-driven NPC).
- Adequate organ and marrow function as defined by routine lab testing including calculated creatinine clearance >60 mL/min, total bilirubin < 1.5x the ULN, ALT and AST <5x the ULN, ANC >1500, and platelets >100,000.
- Measurable disease by RECIST on CT (including a diagnostic CT performed as part of a PET-CT) or MRI available for review.
- Recovered from clinically significant adverse events of most recent anti-cancer therapy prior to enrollment.
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- Cohort 1: In addition to the general inclusion criterion, patients with tumor tissue CPS >1 for whom single agent pembrolizumab is appropriate OR who derived significant clinical benefit from anti-PD-1 therapy (as single agent or combination) in the first line setting. No more than 7 patients with each profile (PD-1 inhibitor naïve vs PD-1 inhibitor experienced with benefit) can be enrolled in the first stage of Cohort 1.
- o Significant clinical benefit is defined as treatment duration >=6 months and/or PR/CR as best objective response prior to disease progression.
- Cohort 1: In addition to the above inclusion criterion, patients must have accessible sites of disease not involving target lesions that are amenable to sequential biopsies, and participants willing to undergo sequential tumor biopsies as long as the treating investigator considers to be clinically safe.
- Cohort 2: In addition to the general inclusion criteria, patients have had progression or recurrence in the relapsed/metastatic setting to PD-1 inhibitors given with or without cytotoxic chemotherapy without significant clinical benefit OR who are candidates for cetuximab monotherapy.
- Significant clinical benefit is defined as treatment duration >=6 months and/or PR/CR as best objective response prior to disease progression.
Who cannot join
- Unknown origin squamous cancer.
- EBV-driven NPC.
- 4 lines or more in the relapsed/metastatic setting.
- Pregnant or lactating, as the effects of NT219 on a fetus or child are unknown. Patients who are capable of childbearing or have partners capable of childbearing must use two forms of birth control including a barrier method to avoid pregnancy.
- Known central nervous system metastases unless previously treated and clinically stable for at least one month.
- Major surgery within 4 weeks or minor surgery within 1 week of starting therapy.
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- Known active HIV infection, unless treated with no detectable virus, or active HIV infection based on screening testing.
- Participants with chronic hepatitis B virus (HBV) infection with active disease that meets the criteria for anti-HBV therapy and are not on suppressive antiviral therapy for at least 4 weeks prior to the first dose of study treatment.
- Patients with known hepatitis C virus (HCV) who have not completed curative antiviral treatment at least 4 weeks prior to first dose of study treatment or have an HCV viral load above the limit of quantification at screening.
- Prior anti-cancer biologic agent within 4 weeks prior to Study Day 1, or prior chemotherapy, targeted small molecular therapy, or radiation therapy within 2 weeks prior to Study Day 1, as wash-out considerations.
- Vaccine administration within 4 weeks before the first dose of NT219
- Serious systemic infection within 4 weeks of the first dose of the study treatment, or clinically significant infection requiring hospitalization and/or IV anti-infective therapy within 2 weeks of the first dose of the study treatment.
- Receipt of any organ transplantation including autologous and allogeneic stem cell transplantation, with the exception of transplants that do not require immunosuppression.
- Diagnosed and/or treated for any other additional malignancy within 2 years of the first dose of study treatment with the exception of curatively treated basal cell or squamous cell carcinoma of the skin and curatively resected in situ cancers. Other exceptions may be considered with the PI's consultation.
- Cohort 1: In addition to the general exclusion criteria, patients with active autoimmune disease requiring systemic treatment in the past two years with use of disease modifying agents, corticosteroids, or immunosuppressive drugs. Replacement therapy such as thyroxine, insulin, or physiologic corticosteroids is allowed. Well-managed or inactive autoimmune disorders, such as Hashimoto's thyroiditis, are allowed at the discretion of the PI.
- Cohort 1: Any condition requiring systemic treatment with >10mg prednisone or equivalent corticosteroid daily or other systemic immunosuppressive medication within 2 weeks of the first dose of study treatment. Topical, intranasal, intrabronchial, and ocular steroids are allowed. Steroids used as premedication for allergic reactions or as prophylactic management of AEs related to the study drugs specific in this protocol are allowed.
- Cohort 2: Any of the following within 6 months of starting study treatment: ST elevation myocardial infarction, severe or unstable angina, uncontrolled cardiac ventricular arrhythmia, coronary or peripheral artery bypass graph or stent, cerebrovascular accident or stroke, or severe/uncontrolled congestive heart failure. Deep vein thrombosis that are hemodynamically stable do not exclude enrollment if the patient has been on a stable dose of anticoagulant for at least three months.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Universtiy of Colorado Hospital
Aurora, Colorado, 80045
UCHealth Highlands Ranch Hospital
Highlands Ranch, Colorado, 80126
About this study
Official title: Phase Ib/II Study of NT219 in Combination With Pembrolizumab or Cetuximab in Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (HNSCC)
Fixed dose NT219 weekly plus pembrolizumab every 3 weeks or cetuximab weekly to be continued until progression, unacceptable toxicity, or investigator or participant decision.
- Being tested
- NT219
- Medical subject headings
- Head and Neck Neoplasms, Squamous Cell Carcinoma of Head and Neck
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NT219Drug
NT219 is a first-in-class small molecule targeting IRS 1/2 and STAT3. Preclinical studies in melanoma have shown NT219 induces PD-L1 expression in vitro and in vivo, resulting in increased efficacy of PD-1 inhibition via synergistic antitumor effect in PD-1 sensitive models and restoration of sensitivity in resistant models. NT219 also synergized with cetuximab in vitro and reversed cetuximab resistance in a head and neck cancer xenograft platform.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 NT219 plus pembrolizumab | Experimental | 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 75 mg/kg IV 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. Receives: Drug: NT219 |
| Cohort 2 NT219 plus cetuximab | Experimental | Cohort 2 will enroll patients who had progression of disease without clinical benefit from PD-1 inhibition or have received ≥2 prior lines of therapy and are good candidates for cetuximab. Patients will be treated with NT219 75mg/kg IV once weekly plus cetuximab given as an initial loading dose of 400 mg/m2 followed by maintenance dosing of 250 mg/m2 once weekly. Receives: Drug: NT219 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate following treatment with NT219 plus pembrolizumab (cohort 1) or cetuximab (cohort 2).
Objective response rate is defined as the percentage of participants who have confirmed best response of complete response or partial response as determined by the investigator. Response will be assessed by RECIST 1.1 or iRECIST (when applicable, cohort 1 only) at baseline (within 28 days of C1D1) and every 9 weeks +/- 10 days while on treatment. All scans during study intervention will be repeated using the same method (CT, PET-CT, or MRI).
Measured: Tumor assessments will be completed every 9 weeks from enrollment/baseline until the final study visit. Additional imaging can occur at 60 days post-treatment +/- 7 days at the discretion of the investigator.
Secondary outcomes (6)
Rate of occurence of dose-limiting toxicity (DLT) within the first 21-day cycle of NT219 plus pembrolizumab (Cohort 1 only)
DLT is defined as any of the following occuring during Cycle 1 of NT219 administered in combination with pembrolizumab: Grade >=3 non-hematologic toxicity, Grade >=4 neutropenia >7 days, Grade >=3 thrombocytopenia with clinically significant bleeding, neutropenic fever, any Hy's law case (AST or ALT >3 x ULN AND total bilirubin >2x ULN AND alk phos <2x ULN AND no other reason for liver injury), and any death not clearly due to underlying disease or extraneous causes. The following Grade >=3 non-hematologic toxicities are NOT considered DLTs: Grade 3 nausea, vomiting, or diarrhea <72 hours with adequate antiemetic and other supportive care; Grade 3 fatigue lasting <7 days; Grade >=3 or higher electrolyte abnormalities lasting up to 72 hours which are not clinically complicated and resolve spontaneously or respond to conventional medical interventions; Grade 3 amylase or lipase elevation not associated with symptoms or clinical manifestations of pancreatitis.
Measured: DLTs will be collected from C1D1 to C1D21 of NT219 plus pembrolizumab
Occurence of treatment-emergent and treatment-related adverse events (AEs) in patients treated with NT219 plus pembrolizumab (cohort 1) or cetuximab (cohort 2).
AEs will be graded according to NCI CTCAE v5.0.
Measured: AEs will be collected from C1D1 until the final study visit
Progression-free survival (PFS) in patients treated with NT219 plus pembrolizumab (Cohort 1) or cetuximab (Cohort 2)
PFS is defined as the time from first dose of NT219 plus pembrolizumab (Cohort 1) or cetuximab (Cohort 2) until investigator-assessed radiographic progressive disease, death, or loss of follow-up, whichever occurs first.
Measured: First dose of NT219 plus pembrolizumab (Cohort 1) or cetuximab (Cohort 2) until progressive disease, death, or loss of follow-up.
Overall survival in patients treated with NT219 plus pembrolizumab (Cohort 1) or cetuximab (Cohort 2)
Overall survival is defined as the time from first dose of NT219 plus pembrolizumab (Cohort 1) or cetuximab (Cohort 2) until death or loss of follow-up, whichever occurs first.
Measured: First dose of NT219 plus pembrolizumab (Cohort 1) or cetuximab (Cohort 2) until death or loss of follow-up.
Duration of response in patients treated with NT219 plus pembrolizumab (Cohort 1) or cetuximab (Cohort 2)
Duration of response is defined as the time from response to NT219 plus pembrolizumab (Cohort 1) or cetuximab (Cohort 2) to progression, death, or loss of clinical follow-up, whichever occurs first.
Measured: Time from response to NT219 plus pembrolizumab (Cohort 1) or cetuximab (Cohort 2) to progression, death, or loss of clinical follow-up.
Clinical benefit rate for patients treated with NT219 plus pembrolizumab (Cohort 1) or cetuximab (Cohort 2)
Clinical benefit rate is defined as the percentage of participants who have confirmed best response of complete response, partial response, or stable disease as determined by the investigator according to RECIST or iRECIST (when applicable, Cohort 1 only).
Measured: Tumor assessments will be completed every 9 weeks from enrollment/baseline until the final study visit. Additional imaging can occur at 60 days post-treatment +/- 7 days at the discretion of the investigator.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Apr 2025
- Study start12 Jun 2025
- Primary completion1 Feb 2030 (estimated)
- Study completionFeb 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Head and Neck CancerStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 29 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Collaborators
- Purple Biotech Ltd.
- Responsible party
- Sponsor
- Investigators
- Alice Weaver, MD, PhD, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06919666
- Sponsor's protocol ID
- 24-0689.cc
- Status last verified
- Jul 2026
- First submitted
- 2 Apr 2025
- Last updated
- 2 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase Ib/II Study of NT219 in Combination With Pembrolizumab or Cetuximab in Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (HNSCC)
- ClinicalTrials.gov ID
- NCT06919666
- Acronym / sponsor ID
- 24-0689.cc
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 29 participants (estimated)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Collaborators
- Purple Biotech Ltd.
- Study start
- 12 Jun 2025 (actual)
- Primary completion
- 1 Feb 2030 (estimated)
- Study completion
- Feb 2031 (estimated)
- First posted
- 9 Apr 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Fixed dose NT219 weekly plus pembrolizumab every 3 weeks or cetuximab weekly to be continued until progression, unacceptable toxicity, or investigator or participant decision.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 NT219 plus pembrolizumab | Experimental | Drug: NT219Cohort 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 75 mg/kg IV 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. |
| Cohort 2 NT219 plus cetuximab | Experimental | Drug: NT219Cohort 2 will enroll patients who had progression of disease without clinical benefit from PD-1 inhibition or have received ≥2 prior lines of therapy and are good candidates for cetuximab. Patients will be treated with NT219 75mg/kg IV once weekly plus cetuximab given as an initial loading dose of 400 mg/m2 followed by maintenance dosing of 250 mg/m2 once weekly. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Age 18 and over.
- ECOG PS 0-2.
- Incurable head and neck squamous cell carcinoma of mucosal origin (oral cavity, tongue, oropharynx, pharynx, larynx, sinonasal and non-EBV-driven NPC).
- Adequate organ and marrow function as defined by routine lab testing including calculated creatinine clearance >60 mL/min, total bilirubin < 1.5x the ULN, ALT and AST <5x the ULN, ANC >1500, and platelets >100,000.
- Measurable disease by RECIST on CT (including a diagnostic CT performed as part of a PET-CT) or MRI available for review.
Key exclusion criteria (17 listed)
- Unknown origin squamous cancer.
- EBV-driven NPC.
- 4 lines or more in the relapsed/metastatic setting.
- Pregnant or lactating, as the effects of NT219 on a fetus or child are unknown. Patients who are capable of childbearing or have partners capable of childbearing must use two forms of birth control including a barrier method to avoid pregnancy.
- Known central nervous system metastases unless previously treated and clinically stable for at least one month.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NT219NT219 is a first-in-class small molecule targeting IRS 1/2 and STAT3. Preclinical studies in melanoma have shown NT219 induces PD-L1 expression in vitro and in vivo, resulting in increased efficacy of PD-1 inhibition via synergistic antitumor effect in PD-1 sensitive models and restoration of sensitivity in resistant models. NT219 also synergized with cetuximab in vitro and reversed cetuximab resistance in a head and neck cancer xenograft platform. | Drug | Cohort 1 NT219 plus pembrolizumab, Cohort 2 NT219 plus cetuximab |
Primary outcome
Objective Response Rate following treatment with NT219 plus pembrolizumab (cohort 1) or cetuximab (cohort 2).
Time frame: Tumor assessments will be completed every 9 weeks from enrollment/baseline until the final study visit. Additional imaging can occur at 60 days post-treatment +/- 7 days at the discretion of the investigator.
Objective response rate is defined as the percentage of participants who have confirmed best response of complete response or partial response as determined by the investigator. Response will be assessed by RECIST 1.1 or iRECIST (when applicable, cohort 1 only) at baseline (within 28 days of C1D1) and every 9 weeks +/- 10 days while on treatment. All scans during study intervention will be repeated using the same method (CT, PET-CT, or MRI).
6 secondary outcomes
Rate of occurence of dose-limiting toxicity (DLT) within the first 21-day cycle of NT219 plus pembrolizumab (Cohort 1 only)
Time frame: DLTs will be collected from C1D1 to C1D21 of NT219 plus pembrolizumab
Occurence of treatment-emergent and treatment-related adverse events (AEs) in patients treated with NT219 plus pembrolizumab (cohort 1) or cetuximab (cohort 2).
Time frame: AEs will be collected from C1D1 until the final study visit
Progression-free survival (PFS) in patients treated with NT219 plus pembrolizumab (Cohort 1) or cetuximab (Cohort 2)
Time frame: First dose of NT219 plus pembrolizumab (Cohort 1) or cetuximab (Cohort 2) until progressive disease, death, or loss of follow-up.
Overall survival in patients treated with NT219 plus pembrolizumab (Cohort 1) or cetuximab (Cohort 2)
Time frame: First dose of NT219 plus pembrolizumab (Cohort 1) or cetuximab (Cohort 2) until death or loss of follow-up.
Duration of response in patients treated with NT219 plus pembrolizumab (Cohort 1) or cetuximab (Cohort 2)
Time frame: Time from response to NT219 plus pembrolizumab (Cohort 1) or cetuximab (Cohort 2) to progression, death, or loss of clinical follow-up.
Clinical benefit rate for patients treated with NT219 plus pembrolizumab (Cohort 1) or cetuximab (Cohort 2)
Time frame: Tumor assessments will be completed every 9 weeks from enrollment/baseline until the final study visit. Additional imaging can occur at 60 days post-treatment +/- 7 days at the discretion of the investigator.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alice Weaver, MD, PhD principal investigator
University of Colorado, Denver
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing NT219 in people with Head and Neck Cancer and Head and Neck Squamous Cell Carcinoma, run by University of Colorado, Denver at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 2 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate following treatment with NT219 plus pembrolizumab (cohort 1) or cetuximab (cohort 2). (time frame: Tumor assessments will be completed every 9 weeks from enrollment/baseline until the final study visit. Additional imaging can occur at 60 days post-treatment +/- 7 days at the discretion of the investigator.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2026.