A Phase 1/2 interventional study of NT219 in Head and Neck Cancer and Head and Neck Squamous Cell Carcinoma, sponsored by University of Colorado, Denver. Active, not recruiting at 2 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-07-02.
Sponsored by University of Colorado, Denver · Phase 1/2, Interventional, and Treatment
Fixed dose NT219 weekly plus pembrolizumab every 3 weeks or cetuximab weekly to be continued until progression, unacceptable toxicity, or investigator or participant decision.
2,344 studies on the registry are indexed under Head and Neck Neoplasms; 551 are open to participants now.
This study's planned enrollment of 29 is below the median of 47 across 1,751 interventional studies indexed under Head and Neck Neoplasms.
Browse Head and Neck Neoplasms studies →University of Colorado, Denver is the lead sponsor of 1,499 studies on the registry; 315 are open to participants now.
Of its 139 completed or terminated interventional studies of FDA-regulated products, 89 (64%) have results posted.
Counted across the registry records on this site, refreshed daily.
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 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.
Exclusion Criteria:
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.
Drug: NT219
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.
Drug: NT219
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.
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).
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.
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.
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).
AEs will be graded according to NCI CTCAE v5.0.
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)
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.
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)
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.
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)
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.
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)
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).
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.
Change from Baseline in Tumor Expression of Immune Biomarkers in patients treated with NT219 plus pembrolizumab (Cohort 1 only)
Baseline and post-treatment tumor tissue will be collected and analyzed for expression of immune biomarkers using immunohistochemistry
Time frame: Baseline tumor tissue collection will occur during the screening window, post-treatment tumor tissue will be collected at C2D8 +/- 2 days
Change from Baseline in Immune Cell Profiles in tumor tissue from patients treated with NT219 plus pembrolizumab (Cohort 1 only)
Baseline and post-treatment tumor tissue will be collected and analyzed for immune cell profiles in tumor and surrounding tissue.
Time frame: Baseline tumor tissue collection will occur during the screening window, post-treatment tumor tissue will be collected at C2D8 +/- 2 days
This study is active, not recruiting, as verified in Jul 2026. You cannot join it, but the record below documents what was studied.
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University of Colorado, Denver