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

Launched by NATIONAL CANCER INSTITUTE (NCI) · May 17, 2025

Keywords

ClinConnect Summary

This clinical trial is exploring whether a combination of two treatments, cemiplimab (REGN2810) and CDX-1140, is more effective than using cemiplimab alone for patients with advanced head and neck cancer. The goal is to see if this combination can help shrink tumors before surgery, potentially allowing for less removal of healthy tissue during the operation. Cemiplimab is an immunotherapy drug that helps the body’s immune system fight cancer, while CDX-1140 is another treatment that may also aid in fighting the tumor.

To participate in this study, patients should be at least 18 years old and have a confirmed diagnosis of stage III or IV head and neck squamous cell carcinoma that can be surgically removed. They should have measurable disease and meet certain health criteria, such as having enough healthy blood cells. Participants can expect to receive treatment before their surgery and will be closely monitored for any side effects. It's important to note that the trial is not yet recruiting participants, and anyone considering joining should speak with their doctor for more details and to see if they qualify.

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ALL

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, nasal cavity and skin) 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) ≥ 8 g/L (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