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 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
3 other identifiers
interventional
44
1 country
5
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Aug 2026
Shorter than P25 for phase_2
5 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 16, 2025
CompletedFirst Posted
Study publicly available on registry
May 20, 2025
CompletedStudy Start
First participant enrolled
August 21, 2026
ExpectedPrimary Completion
Last participant's last visit for primary outcome
November 24, 2027
Study Completion
Last participant's last visit for all outcomes
November 24, 2027
April 16, 2026
April 1, 2026
1.3 years
May 16, 2025
April 15, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
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.
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.
Up to 2 years after surgical resection
Secondary Outcomes (9)
Acute incidence of adverse events
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
From the time of their first treatment with CDX-1140 and/or cemiplimab (REGN2810), up to 2 years after surgical resection
Quantitative pathologic response
Up to 2 years after surgical resection
Tumor infiltrating immune populations
Up to 2 years after surgical resection
Serum cytokines levels
Up to 2 years after surgical resection
- +4 more secondary outcomes
Study Arms (2)
Arm I (Cemiplimab)
ACTIVE COMPARATORPatients 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.
Arm II (CDX-1140 and cemiplimab)
EXPERIMENTALPatients 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
Undergo tumor biopsy
Undergo blood sample collection
Given IV
Undergo CT scan
Undergo PET scan
Given IV
Eligibility Criteria
You may qualify if:
- 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
- +2 more criteria
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (5)
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
Irvine, California, 92612, United States
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, 92868, United States
Emory University Hospital Midtown
Atlanta, Georgia, 30308, United States
Ochsner Medical Center Jefferson
New Orleans, Louisiana, 70121, United States
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, 23298, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Matin Imanguli
JHU Sidney Kimmel Comprehensive Cancer Center LAO
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 16, 2025
First Posted
May 20, 2025
Study Start (Estimated)
August 21, 2026
Primary Completion (Estimated)
November 24, 2027
Study Completion (Estimated)
November 24, 2027
Last Updated
April 16, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
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.