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

Testing a New Treatment for Head and Neck Cancer

NCT: NCT06980038 · Status: RECRUITING · Phase: Phase 2 · Sponsor: National Cancer Institute (NCI) · Started: 2026-08-21 · Est. Completion: 2027-11-24

Plain English Summary

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 is a Phase 2 clinical trial sponsored by National Cancer Institute (NCI) studying 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, Recurrent Head and Neck Squamous Cell Carcinoma, Recurrent Hypopharyngeal Squamous Cell Carcinoma, Recurrent Laryngeal Squamous Cell Carcinoma, Recurrent Nasal Cavity Squamous Cell Carcinoma. This trial tests a new combination of drugs to shrink tumors before surgery. It's for patients with stage III-IV head and neck cancer who are about to have surgery. Participants will receive infusions of the drugs and have biopsies and scans. There are no approved treatments that combine these drugs for this condition. The trial aims to enroll 44 participants.

Official 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Eligible patients must be 18 years or older, have stage III-IV head and neck cancer, and be able to have surgery. Patients with active autoimmune diseases, organ transplants, or other cancers are not eligible. Participants must have measurable disease and be in good general health. Pregnant women and those of childbearing potential must use contraception. This trial is studying 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, Recurrent Head and Neck Squamous Cell Carcinoma, Recurrent Hypopharyngeal Squamous Cell Carcinoma, Recurrent Laryngeal Squamous Cell Carcinoma, Recurrent Nasal Cavity Squamous Cell Carcinoma, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome measures the side effects and effectiveness of the treatment in shrinking tumors before surgery. The specific primary outcome measures are: Incidence of adverse events (AE) (From the time of their first treatment with CDX-1140 and/or cemiplimab (REGN2810), up to 2 years after surgical resection); Major pathologic response (Up to 2 years after surgical resection). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial aims to fill a gap in treatment options for head and neck cancer by combining two immunotherapy drugs. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets 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, Recurrent Head and Neck Squamous Cell Carcinoma, Recurrent Hypopharyngeal Squamous Cell Carcinoma, Recurrent Laryngeal Squamous Cell Carcinoma, Recurrent Nasal Cavity Squamous Cell Carcinoma, where improved treatment options are needed.

Investor Insight

The market for head and neck cancer treatments is growing, with limited options for combination therapies, making this trial potentially significant. Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor if you are eligible and if the treatment could help you. You will receive infusions of the drugs and have biopsies and scans. This trial is currently recruiting participants. The trial is being conducted at 3 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

  • Study Type: INTERVENTIONAL
  • Allocation: RANDOMIZED
  • Model: PARALLEL
  • Masking: NONE
  • Enrollment: 44 participants

Interventions

  • BIOLOGICAL: Anti-CD40 Agonist Monoclonal Antibody CDX-1140 — Given IV
  • PROCEDURE: Biopsy Procedure — Undergo tumor biopsy
  • PROCEDURE: Biospecimen Collection — Undergo blood sample collection
  • BIOLOGICAL: Cemiplimab — Given IV
  • PROCEDURE: Computed Tomography — Undergo CT scan

Primary Outcomes

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

Secondary Outcomes

  • 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)

Full Eligibility Criteria

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 treat

Trial Locations

  • UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care, Irvine, California, United States
  • UC Irvine Health/Chao Family Comprehensive Cancer Center, Orange, California, United States
  • VCU Massey Comprehensive Cancer Center, Richmond, Virginia, United States

Frequently Asked Questions

What is clinical trial NCT06980038?

NCT06980038 is a Phase 2 INTERVENTIONAL study titled "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." It is currently recruiting and is sponsored by National Cancer Institute (NCI). The trial targets enrollment of 44 participants.

What conditions does NCT06980038 study?

This trial investigates treatments for 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, Recurrent Head and Neck Squamous Cell Carcinoma, Recurrent Hypopharyngeal Squamous Cell Carcinoma, Recurrent Laryngeal Squamous Cell Carcinoma, Recurrent Nasal Cavity Squamous Cell Carcinoma. The primary condition under study is Head and Neck Squamous Cell Carcinoma.

What treatments are being tested in NCT06980038?

The interventions being studied include: Anti-CD40 Agonist Monoclonal Antibody CDX-1140 (BIOLOGICAL), Biopsy Procedure (PROCEDURE), Biospecimen Collection (PROCEDURE), Cemiplimab (BIOLOGICAL), Computed Tomography (PROCEDURE). Given IV

What does Phase 2 mean for NCT06980038?

Phase 2 trials test whether the treatment works for the intended condition. They involve 100-300 patients and continue to evaluate safety while measuring effectiveness.

What is the current status of NCT06980038?

This trial is currently "Recruiting." It started on 2026-08-21. The estimated completion date is 2027-11-24.

Who is sponsoring NCT06980038?

NCT06980038 is sponsored by National Cancer Institute (NCI). The sponsor is responsible for funding, designing, and overseeing the clinical trial.

How many people can participate in NCT06980038?

The trial aims to enroll 44 participants. The trial is currently recruiting and accepting new participants.

How is NCT06980038 designed?

This is a interventional study, uses randomized allocation, follows a parallel design, employs none masking.

What are the primary outcomes being measured in NCT06980038?

The primary outcome measures are: Incidence of adverse events (AE) (From the time of their first treatment with CDX-1140 and/or cemiplimab (REGN2810), up to 2 years after surgical resection); Major pathologic response (Up to 2 years after surgical resection). These are the main endpoints researchers use to determine whether the treatment is effective.

Where is NCT06980038 being conducted?

This trial is being conducted at 3 sites, including Irvine, California; Orange, California; Richmond, Virginia (United States).

Where can I find official information about NCT06980038?

The official record for NCT06980038 is available on ClinicalTrials.gov at https://clinicaltrials.gov/study/NCT06980038. This government database provides the most up-to-date and detailed information about the trial.

What is NCT06980038 testing in simple terms?

This trial tests a new combination of drugs to shrink tumors before surgery. It's for patients with stage III-IV head and neck cancer who are about to have surgery.

Why is this trial significant?

This trial aims to fill a gap in treatment options for head and neck cancer by combining two immunotherapy drugs.

What are the potential risks of participating in NCT06980038?

Side effects may include fatigue, nausea, and changes in blood counts. Monitor for signs of infection and report any new symptoms to your healthcare provider. As with any clinical trial, participants are closely monitored and can withdraw at any time.

Should I consider participating in NCT06980038?

Ask your doctor if you are eligible and if the treatment could help you. You will receive infusions of the drugs and have biopsies and scans. Always discuss clinical trial participation with your healthcare provider to determine if it is appropriate for your specific situation.

What does NCT06980038 signal from an investment perspective?

The market for head and neck cancer treatments is growing, with limited options for combination therapies, making this trial potentially significant. This is a Phase 2 trial, which is focused on confirming efficacy before larger pivotal studies.

What happens if the treatment in this trial doesn't work?

Participants will receive infusions of the drugs and have biopsies and scans. Participants in clinical trials always have the right to withdraw and pursue alternative treatments. The study team will help transition patients to other available options.

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This analysis is AI-generated and does not constitute medical advice. Always consult your healthcare provider before making decisions about clinical trial participation.