Head and Neck Squamous Cell CarcinomaPhase 2NCT06980038
Testing Whether Cemiplimab (REGN2810) Plus CDX-1140 Given Prior to Surgery Are Better Than Cemiplimab (REGN2810) Alone in Patients With Stage III-IV Head and Neck Cancer
A Phase 2 study testing Anti-CD40 Agonist Monoclonal Antibody CDX-1140, Biopsy Procedure and Biospecimen Collection in people with Head and Neck Squamous Cell Carcinoma and Hypopharyngeal Squamous Cell Carcinoma, run by National Cancer Institute (NCI) at 12 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Head and Neck Squamous Cell Carcinoma, Hypopharyngeal Squamous Cell Carcinoma, Laryngeal Squamous Cell Carcinoma
- What is being tested?
- Anti-CD40 Agonist Monoclonal Antibody CDX-1140, Biopsy Procedure and Biospecimen Collection
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- 12 sitesUnited States
- Study dates
- 27 May 2026to 24 Nov 2027
- Phase
- Phase 2
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
- 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)
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- 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
Who cannot join
- 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)
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- 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
Trial locations and contacts
12 sites in 1 country. Contact the study team or a site near you to ask about taking part.
12 sites in 1 country
United States12 sites, 12 recruiting
- Recruiting
Emory University Hospital Midtown
Atlanta, Georgia, 30308
Site Public Contact, 888-946-7447
Jose A. Monteiro de Oliveira Novaes
- Recruiting
University of Cincinnati Cancer Center-UC Medical Center
Cincinnati, Ohio, 45219
Site Public Contact, 513-584-7698, cancer@uchealth.com
Chad A. Zender
- Recruiting
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Site Public Contact, 551-996-2897
Robert S. Alter
- Recruiting
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
Irvine, California, 92612
Site Public Contact, 877-827-8839, ucstudy@uci.edu
Victoria M. Villaflor
- Recruiting
Los Angeles General Medical Center
Los Angeles, California, 90033
Site Public Contact, 323-865-0451, uscnorrisinfo@med.usc.edu
Jacob S. Thomas
- Recruiting
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033
Site Public Contact, 323-865-0451
Jacob S. Thomas
- Recruiting
Ochsner Medical Center Jefferson
New Orleans, Louisiana, 70121
Site Public Contact, 504-842-8084, Elisemarie.curry@ochsner.org
Daniel Johnson
- Recruiting
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, 92868
Site Public Contact, 877-827-8839, ucstudy@uci.edu
Victoria M. Villaflor
- Recruiting
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
Site Public Contact, 412-647-8073
Kevin J. Contrera
- Recruiting
Oregon Health and Science University
Portland, Oregon, 97239
Site Public Contact, 503-494-1080, trials@ohsu.edu
Jeremy P. Cetnar
- Recruiting
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, 23298
Site Public Contact, 804-628-6430, CTOclinops@vcu.edu
Erin R. Alesi
- Recruiting
University of Cincinnati Cancer Center-West Chester
West Chester, Ohio, 45069
Site Public Contact, 513-584-7698, cancer@uchealth.com
Chad A. Zender
About this study
Official title: A Phase 2 Window of Opportunity Trial of Neoadjuvant Agonistic Anti-CD40 Antibody CDX-1140 and Cemiplimab (REGN2810) in AJCC Stage III-IV Head and Neck Cancer Patients Prior to Surgery
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.
Read the detailed description
PRIMARY OBJECTIVE:
- To evaluate major pathologic response rate (defined as ≤ 10% of residual viable tumor) of anti-CD40 agonist monoclonal antibody CDX-1140 (CDX-1140) combined with cemiplimab (REGN2810) compared with cemiplimab (REGN2810) alone.
SECONDARY OBJECTIVES:
- Evaluate the rate of any pathologic response of CDX-1140 in combination with cemiplimab (REGN2810).
II. To evaluate toxicity and tolerability of CDX-1140 and programmed cell death protein 1 (PD-1) blockade combination in neoadjuvant (pre-surgical) setting.
III. To compare gene expression profiles by ribonucleic acid (RNA) sequencing (RNAseq) between CDX-1140 and control groups as well as correlate gene expression with pathologic response.
IV. To evaluate circulating tumor deoxyribonucleic acid (DNA) (ctCNA) as a biomarker of response to neoadjuvant immunotherapy V. To evaluate the pharmacokinetics (PK) of CDX-1140 and cemiplimab (REGN2810) used in combination (arm 2) and the relationship of outcomes to baseline and time-varying clearance of both agents.
EXPLORATORY OBJECTIVES:
- To evaluate dynamic changes in tumor microenvironment (TME) and circulating immune cell populations.
Ia. To compare dynamic changes in TME while on treatment with subsequent pathologic response in the final specimen.
II. To evaluate changes in circulating plasma cytokines pre and post neoadjuvant immunotherapy with CDX-1140 and cemiplimab (REGN2810).
III. To correlate major pathologic response with the level of programmed cell death ligand 1 (PD-L1) expression.
IV. To explore the correlation of pathologic response to disease free recurrence and overall survival at 2 years after surgery.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive cemiplimab intravenously (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 computed tomography (CT) scan, positron emission tomography (PET) during screening and tumor biopsy and blood sample collection throughout the study.
ARM II: 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.
After completion of study treatment, patients are followed up at week 9-10, week 18, at 6 months and every 3-6 months for 2 years after surgery.
- 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, Oropharyngeal Squamous Cell Carcinoma
- Being tested
- Anti-CD40 Agonist Monoclonal Antibody CDX-1140, Biopsy Procedure, Biospecimen Collection, Cemiplimab, Computed Tomography
- Medical subject headings
- Squamous Cell Carcinoma of Head and Neck, Laryngeal Neoplasms, Mouth Neoplasms, Nasopharyngeal Carcinoma, Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Anti-CD40 Agonist Monoclonal Antibody CDX-1140Biological
Also called Agonist CD40 Antibody CDX-1140, Anti-CD40 Agonistic Monoclonal Antibody CDX-1140, CDX 1140, CDX-1140
Given IV
Biopsy ProcedureProcedure or surgery
Also called Biopsy, BIOPSY_TYPE, Bx
Undergo tumor biopsy
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection
Undergo blood sample collection
CemiplimabBiological
Also called Cemiplimab RWLC, Cemiplimab-rwlc, Libtayo, REGN 2810
Given IV
Computed TomographyProcedure or surgery
Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography
Undergo CT scan
Positron Emission TomographyProcedure or surgery
Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)
Undergo PET scan
Tumor ResectionProcedure or surgery
Undergo resection surgery
| Study group | Role | What they receive |
|---|---|---|
| Arm I (Cemiplimab) | Active comparator | 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. Receives: Procedure: Biospecimen Collection; Biological: Cemiplimab; Procedure: Computed Tomography; Procedure: Positron Emission Tomography; Procedure: Tumor Resection |
| Arm II (CDX-1140 and cemiplimab) | Experimental | 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. Receives: Biological: Anti-CD40 Agonist Monoclonal Antibody CDX-1140; Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Biological: Cemiplimab; Procedure: Computed Tomography; Procedure: Positron Emission Tomography; Procedure: Tumor Resection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of adverse events (AE)
Will be assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Descriptive statistics will be used.
Measured: From the time of their first treatment with CDX-1140 and/or cemiplimab (REGN2810), up to 2 years after surgical resection
Major pathologic response
Defined as ≤ 10% of viable tumor area relative to total tumor area.
Measured: Up to 2 years after surgical resection
Secondary outcomes (9)
Acute incidence of adverse events
Will be assessed using NCI CTCAE version 5.0. Descriptive statistics will be used.
Measured: From the time of their first treatment with CDX-1140 and/or cemiplimab (REGN2810), up to 2 years after surgical resection
Late incidence of adverse events
Will be assessed using NCI CTCAE version 5.0. Descriptive statistics will be used.
Measured: From the time of their first treatment with CDX-1140 and/or cemiplimab (REGN2810), up to 2 years after surgical resection
Quantitative pathologic response
Two-sample t-test, Mann-Whitney U test, or log rank test will be used where appropriate to analyze the correlation between efficacy outcomes.
Measured: Up to 2 years after surgical resection
Tumor infiltrating immune populations
Two-sample t-test, Mann-Whitney U test, or log rank test will be used where appropriate to analyze the correlation between efficacy outcomes.
Measured: Up to 2 years after surgical resection
Serum cytokines levels
Two-sample t-test, Mann-Whitney U test, or log rank test will be used where appropriate to analyze the correlation between efficacy outcomes.
Measured: Up to 2 years after surgical resection
Circulating tumor deoxyribonucleic acid (ctDNA) levels
Two-sample t-test, Mann-Whitney U test, or log rank test will be used where appropriate to analyze the correlation between efficacy outcomes. Will also compare ctDNA levels between the two arms and between responders and non-responders using a Student's t-test.
Measured: Up to 2 years after surgical resection
Gene expression levels
Will be assessed using DEseq2, and will also be compared between treatment arms and between those with and without achieving pathologic response.
Measured: Day 3 and day 29-36
Gene set enrichment
Gene set statistics will be run with fgsea using MSigDb61 pathways annotated in the HALLMARK databases.
Measured: Up to 2 years after surgical resection
Pharmacokinetic (PK) parameters
Including clearance and area-under-the-curve, will be calculated for cemiplimab (REGN2810) and CDX-1140 in combination. Impact of baseline and time-varying clearance of cemiplimab (REGN2810) and CDX-1140 in combination will be correlated to efficacy data and AEs to evaluate any PK-related efficacy or toxicity relationship. Also, comparison of observed cemiplimab (REGN2810) PK with historical data will be included.
Measured: Up to study completion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 May 2025
- Study start27 May 2026
- Primary completion24 Nov 2027 (estimated)
- Study completion24 Nov 2027 (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 Squamous Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 44 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Matin Imanguli, Principal investigator, JHU Sidney Kimmel Comprehensive Cancer Center LAO
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06980038
- Sponsor's protocol ID
- NCI-2025-03539
- Other IDs
- NCI-2025-03539, 10706, 10706, UM1CA186691
- Status last verified
- May 2026
- First submitted
- 16 May 2025
- Last updated
- 16 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.