Recruiting
Phase 2

Cemiplimab & CDX-1140

Sponsor:

National Cancer Institute (NCI)

Code:

NCT06980038

Conditions

Head and Neck Squamous Cell Carcinoma

Hypopharyngeal Squamous Cell Carcinoma

Laryngeal Squamous Cell Carcinoma

Nasal Cavity Squamous Cell Carcinoma

Oral Cavity Squamous Cell Carcinoma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Anti-CD40 Agonist Monoclonal Antibody CDX-1140

Biopsy Procedure

Biospecimen Collection

Cemiplimab

Computed Tomography

Study Details

Brief summary:

This phase II trial compares the effectiveness of cemiplimab with CDX-1140 to cemiplimab without CDX-1140 prior to surgery in treating patients with stage III-IV head and neck cancer. Immunotherapy with monoclonal antibodies, such as cemiplimab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. CDX-1140 is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Giving cemiplimab with CDX-1140 versus cemiplimab alone before surgery may make the tumor smaller and may reduce the amount of normal tissue that needs to be removed for patients with stage III-IV head and neck cancer.

Conditions

Head and Neck Squamous Cell Carcinoma

Hypopharyngeal Squamous Cell Carcinoma

Laryngeal Squamous Cell Carcinoma

Nasal Cavity Squamous Cell Carcinoma

Oral Cavity Squamous Cell Carcinoma

Study ID

NCT06980038

Start date

May 27, 2026

Status verified date

May, 2026

Completion date

Nov 24, 2027

Anticipated

Primary completion date

Nov 24, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Patients must have histologically or cytologically confirmed American Joint Committee on Cancer (AJCC) stage III-IV T0-4, N0-3b, M0 mucosal head and neck squamous cell carcinoma (HNSCC) (oral cavity, oropharynx, larynx, hypopharynx, and nasal cavity) that is appropriate for surgical resection. Both previously untreated (primary) and recurrent (salvage) settings will be eligible. Tumors must be accessible to biopsy in clinic (patients with laryngeal, hypopharyngeal, nasal cavity and base of tongue tumors will have endoscopic biopsies)
  • For patients with oropharyngeal cancer, only p16-negative (non-human papillomavirus \[HPV\] related) patients will be eligible
  • Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥ 20 mm (≥ 2 cm) by chest x-ray or as ≥ 10 mm (≥ 1 cm) with CT scan, MRI, or calipers by clinical exam
  • Age ≥ 18 years. Because no dosing or adverse event (AE) data are currently available on the use of cemiplimab (REGN2810) alone or in combination with CDX-1140 in patients < 18 years of age, children are excluded from this study
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%)
  • Hemoglobin (Hb) ≥ 7 g/dL (transfusion allowed to bring Hb to this level)
  • Absolute neutrophil count ≥ 1,000/mcL
  • Platelets ≥ 100,000/mcL
  • Total bilirubin ≤ 1.5 × institutional upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) /alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3 × institutional ULN
  • Creatinine ≤ 1.5 × institutional ULN OR glomerular filtration rate (GFR) ≥ 60 mL/min/1.73 m\^2
  • Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
  • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
  • Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
  • Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class II or better
  • Based on its mechanism of action, cemiplimab (REGN2810) can cause fetal harm when administered to a pregnant woman. Animal studies have demonstrated that inhibition of the PD-1/PD-L1 pathway can lead to increased risk of immune-mediated rejection of the developing fetus resulting in fetal death. Women of childbearing potential and men should use effective contraception during treatment with cemiplimab (REGN2810) and for 4 months after the last dose. The reproductive and developmental toxicity of CDX-1140 has not been evaluated. Women of childbearing potential and their partners who receive CDX-1140 must therefore take adequate contraceptive measures
  • Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants

Exclusion Criteria:

  • Active or documented history of autoimmune disease within 2 years before screening
  • Prior or planned allogeneic hematopoietic stem cell transplantation (HSCT)
  • History of organ transplant that requires use of immunosuppressive medications
  • Current or prior use of immunosuppressive medication within 14 days prior to the start of study drug administration. Immunosuppressants may interfere with study drug efficacy
  • Any previous treatment with a PD-1 or PD-L1 inhibitor, including cemiplimab (REGN2810). It is unclear how prior exposure to immunotherapy would impact future use of checkpoint inhibitors
  • Concurrent use of prednisone (10 mg or more)
  • Patients with new pulmonary infiltrates indicative of pneumonitis, history of (non-infectious) pneumonitis/interstitial lung disease, or current pneumonitis/interstitial lung disease, including grade 1 pneumonitis (i.e., asymptomatic, clinical or diagnostic observation only, intervention not indicated)
  • Another active malignancy for which the natural history or treatment has potential to interfere with the safety or efficacy assessment of the investigational regimen on this trial
  • Patients who have not recovered from AE due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1) with the exception of alopecia
  • Patients who are receiving any other investigational agents, such as concurrent chemotherapy, biologic, immunologic or hormonal therapy for cancer treatment
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to CDX-1140 or cemiplimab (REGN2810)
  • Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous
  • Pregnant women are excluded from this study because of the increased risk of immune-mediated rejection of the developing fetus with cemiplimab (REGN2810). Because of the potential for serious adverse reactions in breastfed children, women should not breastfeed during treatment with cemiplimab (REGN2810) and for at least 4 months after the last dose. These risks may also apply to CDX-1140

Study Design

Enrollment

44 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

active comparator: Arm I (Cemiplimab)

Patients receive cemiplimab IV over 30 minutes on day 1. Patients then undergo standard of care surgical resection on day 29-36 and receive standard of care adjuvant therapy. Treatment is given in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, PET during screening and tumor biopsy and blood sample collection throughout the study.

experimental: Arm II (CDX-1140 and cemiplimab)

Patients receive CDX-1140 IV over 90 minutes on day 1 and cemiplimab IV over 30 minutes on day 4. Patients then undergo standard of care surgical resection on day 29-36 and receive standard of care adjuvant therapy. Treatment is given in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, PET during screening and tumor biopsy and blood sample collection throughout the study.

Interventions

Anti-CD40 Agonist Monoclonal Antibody CDX-1140

Given IV

Biopsy Procedure

Undergo tumor biopsy

Biospecimen Collection

Undergo blood sample collection

Cemiplimab

Given IV

Computed Tomography

Undergo CT scan

Positron Emission Tomography

Undergo PET scan

Tumor Resection

Undergo resection surgery

Primary outcome measure

  • Incidence of adverse events (AE) [ Time Frame: From the time of their first treatment with CDX-1140 and/or cemiplimab (REGN2810), up to 2 years after surgical resection ]
  • Major pathologic response [ Time Frame: Up to 2 years after surgical resection ]

Central Contacts and Locations

Locations

UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care

Recruiting

Irvine, California, United States, 92612

Contacts

Site Public Contact

877-827-8839ucstudy@uci.edu

Principal Investigator:

Victoria M. Villaflor

Los Angeles General Medical Center

Recruiting

Los Angeles, California, United States, 90033

Contacts

Site Public Contact

323-865-0451uscnorrisinfo@med.usc.edu

Principal Investigator:

Jacob S. Thomas

USC / Norris Comprehensive Cancer Center

Recruiting

Los Angeles, California, United States, 90033

Contacts

Site Public Contact

323-865-0451

Principal Investigator:

Jacob S. Thomas

UC Irvine Health/Chao Family Comprehensive Cancer Center

Recruiting

Orange, California, United States, 92868

Contacts

Site Public Contact

877-827-8839ucstudy@uci.edu

Principal Investigator:

Victoria M. Villaflor

Emory University Hospital Midtown

Recruiting

Atlanta, Georgia, United States, 30308

Contacts

Site Public Contact

888-946-7447

Principal Investigator:

Jose A. Monteiro de Oliveira Novaes

Ochsner Medical Center Jefferson

Recruiting

New Orleans, Louisiana, United States, 70121

Contacts

Site Public Contact

504-842-8084Elisemarie.curry@ochsner.org

Principal Investigator:

Daniel Johnson

University of Cincinnati Cancer Center-UC Medical Center

Recruiting

Cincinnati, Ohio, United States, 45219

Contacts

Site Public Contact

513-584-7698cancer@uchealth.com

Principal Investigator:

Chad A. Zender

University of Cincinnati Cancer Center-West Chester

Recruiting

West Chester, Ohio, United States, 45069

Contacts

Site Public Contact

513-584-7698cancer@uchealth.com

Principal Investigator:

Chad A. Zender

Oregon Health and Science University

Recruiting

Portland, Oregon, United States, 97239

Contacts

Site Public Contact

503-494-1080trials@ohsu.edu

Principal Investigator:

Jeremy P. Cetnar

UPMC Hillman Cancer Center

Recruiting

Pittsburgh, Pennsylvania, United States, 15232

Contacts

Site Public Contact

412-647-8073

Principal Investigator:

Kevin J. Contrera

VCU Massey Comprehensive Cancer Center

Recruiting

Richmond, Virginia, United States, 23298

Contacts

Site Public Contact

804-628-6430CTOclinops@vcu.edu

Principal Investigator:

Erin R. Alesi

More Information

Sponsor

National Cancer Institute (NCI)

Last update posted

Sep 8, 2026

Last verified

May, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by National Cancer Institute (NCI) on 2026-09-08.