NT219 Combined With Standard of Care Biologic Therapy in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma

NCT06919666 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 24-0689.cc
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Head and Neck Cancer; Head and Neck Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• 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).

  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)

  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 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)

  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)

  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 from response to NT219 plus pembrolizumab (Cohort 1) or cetuximab (Cohort 2) to progression, death, or loss of clinical follow-up.

Other Outcomes (2)

• Change from Baseline in Tumor Expression of Immune Biomarkers in patients treated with NT219 plus pembrolizumab (Cohort 1 only)

  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 tumor tissue collection will occur during the screening window, post-treatment tumor tissue will be collected at C2D8 +/- 2 days

Study Arms (2)

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.

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.

Drug: NT219

Interventions

NT219 DRUG

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.

Cohort 1 NT219 plus pembrolizumab; Cohort 2 NT219 plus cetuximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• o Significant clinical benefit is defined as treatment duration \>=6 months and/or PR/CR as best objective response prior to disease progression.
• Significant clinical benefit is defined as treatment duration \>=6 months and/or PR/CR as best objective response prior to disease progression.

You may not qualify if:

• Unknown origin squamous cancer.
• EBV-driven NPC.
• 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.
• 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: 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.

Sponsors & Collaborators

• University of Colorado, Denver: lead
• Purple Biotech Ltd.: collaborator

Study Sites (2)

Universtiy of Colorado Hospital

Aurora, Colorado, 80045, United States

RECRUITING

UCHealth Highlands Ranch Hospital

Highlands Ranch, Colorado, 80126, United States

RECRUITING

MeSH Terms

Conditions

Head and Neck Neoplasms; Squamous Cell Carcinoma of Head and Neck

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Study Officials

• Alice Weaver, MD, PhD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 2, 2025
• First Posted: April 9, 2025
• Study Start: June 12, 2025
• Primary Completion (Estimated): February 1, 2030
• Study Completion (Estimated): February 1, 2031
• Last Updated: December 22, 2025

Record last verified: 2025-12

Locations

US (2)