Sinonasal Squamous Cell CarcinomaPhase 2NCT07281417

Testing the Addition of Cemiplimab (REGN2810) to Chemotherapy Treatment Given Prior to Surgery in Patients With Sinonasal Squamous Cell Carcinoma

A Phase 2 study testing Biopsy Procedure, Biospecimen Collection and Carboplatin in people with Sinonasal Squamous Cell Carcinoma and Stage III Sinonasal Cancer AJCC v8, run by National Cancer Institute (NCI) at 18 sites in United States.

Recruiting

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Sites and contacts

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Sinonasal Squamous Cell Carcinoma, Stage III Sinonasal Cancer AJCC v8, Stage IVA Sinonasal Cancer AJCC v8
What is being tested?: Biopsy Procedure, Biospecimen Collection and Carboplatin
Type of treatment: Injection or infusion, Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 108 participants
Where: 18 sitesUnited States
Study dates: 1 Sep 2026to 16 Dec 2030
Phase: Phase 2
Are there results?: Not yet: the study is under way

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 confirmed squamous cell carcinoma of sinonasal origin
Patients must have a T stage (T3, T4a, and select T4b) primary tumor according to American Joint Committee on Cancer (AJCC) 8th edition. 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
No evidence of metastatic disease determined by pre-treatment imaging. Metastatic disease to neck nodes is considered locally advanced and therefore allowable. Patients with N0 and N1-3 disease will be eligible
Known HPV status (i.e., HPV negative, p16 immunohistochemistry [IHC] positive, high risk [HR]-HPV in situ hybridization [ISH] positive) from testing performed prior to referral. HPV status data (e.g., date of test, type of test [p16 IHC or HR-HPV ISH] and testing result) must be collected during enrollment. Patients who do not have this information available for collection will not be enrolled on this study
Age ≥ 18 years
Because no dosing or adverse event data are currently available on the use of cemiplimab (REGN2810) in combination with carboplatin and paclitaxel in patients < 18 years of age, children are excluded from this study

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Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%)
Hemoglobin ≥ 8 g/dL (acceptable to reach via transfusion)
Absolute neutrophil count ≥ 1,500/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 glutamate pyruvate transaminase [SGPT]) ≤ 3 × institutional ULN
Creatinine clearance ≥ 40 mL/min
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 a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
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. For this reason and because paclitaxel is a class D agent with the potential for teratogenic or abortifacient effects, women of childbearing potential (WCBP) and men should use highly effective contraception during treatment and for 6 months after the last dose of the study drugs. WCBP and men should avoid donating eggs/sperm during treatment and for 6 months after the last dose of the study drugs. Women should discontinue nursing during treatment and for 6 months after the last dose of the study drugs
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
Prior to enrollment, verification of payment coverage by insurance (or other payment) for neoadjuvant paclitaxel and carboplatin chemotherapy must be obtained

Who cannot join

Patients with unresectable disease
Patients presenting with T3 disease without the need for maxillectomy and/or orbital invasion requiring orbital dissection/resection
Patients who have had any previous systemic therapy to the index lesion in the past 12 months. This includes cemiplimab (REGN2810) and/or other immune modulating agents. Previous systemic therapy may alter or affect response
Patients who had palliative RT (< 20 Gy) within 1 week prior to entering the study
Ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest risk for immune-mediated adverse events (imAEs)
History of pneumonitis within the last 5 years

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Patients who have not recovered from adverse events (AEs) 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
History of allergic reactions attributed to compounds of similar chemical or biologic composition to cemiplimab (REGN2810) or carboplatin and paclitaxel
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). Men and WCBP who are not prepared to use highly effective contraception during and for 6 months after completion of treatment are excluded from this study

Trial locations and contacts

18 sites in 1 country. Contact the study team or a site near you to ask about taking part.

City, postcode or hospital

Sites recruiting now only

18 sites in 1 country

United States18 sites, 18 recruiting

Emory University Hospital Midtown
Atlanta, Georgia, 30308
Site Public Contact, 888-946-7447
Jose A. Monteiro de Oliveira Novaes
Recruiting
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599
Site Public Contact, 877-668-0683, cancerclinicaltrials@med.unc.edu
Siddharth Sheth
Recruiting
University of Virginia Cancer Center
Charlottesville, Virginia, 22908
Site Public Contact, 434-243-6303, uvacancertrials@hscmail.mcc.virginia.edu
Varinder Kaur
Recruiting
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
Irvine, California, 92612
Site Public Contact, 877-827-8839, ucstudy@uci.edu
Edward Kuan
Recruiting
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536
Site Public Contact, 859-257-3379
Susanne M. Arnold
Recruiting
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033
Site Public Contact, 323-865-0451
Jacob S. Thomas
Recruiting
Yale University
New Haven, Connecticut, 06520
Site Public Contact, 203-785-5702, canceranswers@yale.edu
Aarti Bhatia
Recruiting
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, 92868
Site Public Contact, 877-827-8839, ucstudy@uci.edu
Edward Kuan
Recruiting
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
Site Public Contact, 412-647-8073
Dan P. Zandberg
Recruiting
Moffitt Cancer Center at SouthShore
Ruskin, Florida, 33570
Site Public Contact, 800-679-0775, ClinicalTrials@moffitt.org
Jimmy J. Caudell
Recruiting
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817
Site Public Contact, 916-734-3089
Shiruyeh Schokrpur
Recruiting
Moffitt Cancer Center-International Plaza
Tampa, Florida, 33607
Site Public Contact, 800-679-0775, ClinicalTrials@moffitt.org
Jimmy J. Caudell
Recruiting
Moffitt Cancer Center - McKinley Campus
Tampa, Florida, 33612
Site Public Contact, 800-679-0775, ClinicalTrials@moffitt.org
Jimmy J. Caudell
Recruiting
Moffitt Cancer Center
Tampa, Florida, 33612
Site Public Contact, 800-679-0775, ClinicalTrials@moffitt.org
Jimmy J. Caudell
Recruiting
Smilow Cancer Hospital Care Center-Trumbull
Trumbull, Connecticut, 06611
Site Public Contact, 203-785-5702, canceranswers@yale.edu
Aarti Bhatia
Recruiting
Smilow Cancer Hospital-Waterbury Care Center
Waterbury, Connecticut, 06708
Site Public Contact, 203-785-5702, canceranswers@yale.edu
Aarti Bhatia
Recruiting
Smilow Cancer Hospital Care Center - Waterford
Waterford, Connecticut, 06385
Site Public Contact, 203-785-5702, canceranswers@yale.edu
Aarti Bhatia
Recruiting
Moffitt Cancer Center at Wesley Chapel
Wesley Chapel, Florida, 33544
Site Public Contact, 800-679-0775, ClinicalTrials@moffitt.org
Jimmy J. Caudell
Recruiting

Other trials in United States

About this study

Official title: Neoadjuvant Chemotherapy With or Without Cemiplimab (REGN2810) in Sinonasal Squamous Cell Carcinoma: A Randomized Phase 2 Study

This phase II trial compares the effect of chemotherapy (carboplatin and paclitaxel) with versus without cemiplimab given before surgery (neoadjuvant) in patients with sinonasal squamous cell cancer. Carboplatin is in a class of medications known as platinum-containing compounds. Carboplatin works by killing, stopping or slowing the growth of cancer cells. Paclitaxel is in a class of medications called antimicrotubule agents. It stops cancer cells from growing and dividing and may kill them. 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. The usual approach for patients with sinonasal squamous cell cancer is surgery followed by radiation therapy, with or without chemotherapy. Recently, some patients have also been treated with neoadjuvant chemotherapy before surgery. Adding cemiplimab to chemotherapy before surgery may be more effective at stopping the cancer from growing or spreading, compared to chemotherapy alone.

Read the detailed description

PRIMARY OBJECTIVE:

To assess whether neoadjuvant therapy (NAT) with cemiplimab (REGN2810)/carboplatin/paclitaxel (Arm 1) results in improved event free survival (EFS) compared to carboplatin/paclitaxel (Arm 2) in participants with sinonasal squamous cell carcinoma (SNSCC).

SECONDARY OBJECTIVES:

To compare objective response rate (ORR) between neoadjuvant cemiplimab (REGN2810)/carboplatin/paclitaxel (Arm 1) and neoadjuvant carboplatin/paclitaxel (Arm 2) and to historical standard of care (SOC) in participants with SNSCC.

II. To compare overall survival (OS) between neoadjuvant cemiplimab (REGN2810)/carboplatin/paclitaxel (Arm 1) and carboplatin/paclitaxel (Arm 2) and to historical SOC in participants with SNSCC.

III. To characterize toxicity with NAT in SNSCC. IV. To measure changes in T-cell clonality/diversity using ribonucleic acid (RNA) sequencing (RNAseq) and correlate with NAT response and EFS.

To evaluate organ preservation (orbital and skull base) rate with NAT in SNSCC.

CORRELATIVE OBJECTIVES:

To correlate human papillomavirus (HPV) status with ORR and OS after NAT. II. To correlate combined positive score (CPS) for PD-L1 expression with OS and EFS.

III. To measure the kinetics of circulating tumor DNA (ctDNA) pre- and post-NAT and correlate with ORR and OS after NAT.

IV. To correlate change in Sinonasal Morbidity Score with ORR and EFS after NAT.

To conduct DNA sequencing on pre-treatment tumor biopsies to determine whether features of the tumor genomic landscape are associated with response to NAT.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM 1:

NAT: Patients receive cemiplimab intravenously (IV) over 30 minutes on day 1 of each cycle, carboplatin IV over 30 minutes on day 1 of each cycle, and paclitaxel IV over 180 minutes on day 1 of each cycle. Cycles repeat every 21 days (3 weeks) for up to 2 cycles (6 weeks) in the absence of disease progression or unacceptable toxicity. At the discretion of the investigator, patients may alternatively receive carboplatin IV over 30 minutes and paclitaxel IV over 60 minutes weekly during the 2, 3-week cycles. Up to 14 days after completion of NAT, patients are evaluated for response and proceed to definitive therapy.

DEFINITIVE THERAPY: Patients with complete response (CR) or partial response (PR) receive concurrent SOC chemoradiotherapy (CRT). Patients with stable disease (SD) or progressive disease (PD) undergo surgery within 6 weeks of completion of NAT followed by SOC adjuvant therapy.

ADJUVANT THERAPY: Within 3-4 weeks of NAT or 4-6 weeks of surgery, patients undergo radiation therapy (RT) once daily, 5 days per week for a total of 30 fractions over 6 weeks and receive cisplatin or carboplatin weekly during RT.

Patients also undergo magnetic resonance imaging (MRI), positron emission tomography (PET)/computed tomography (CT), CT, and collection of blood samples throughout the trial. Patients may undergo biopsy pre-treatment and/or on study.

ARM 2:

NAT: Patients receive carboplatin IV over 30 minutes on day 1 of each cycle and paclitaxel IV over 180 minutes on day 1 of each cycle. Cycles repeat every 21 days (3 weeks) for up to 2 cycles (6 weeks) in the absence of disease progression or unacceptable toxicity. At the discretion of the investigator, patients may alternatively receive carboplatin IV over 30 minutes and paclitaxel IV over 60 minutes weekly during the 2, 3-week cycles. Up to 14 days after completion of NAT, patients are evaluated for response and proceed to definitive therapy.

DEFINITIVE THERAPY: Patients with CR or PR receive concurrent SOC CRT. Patients with SD or PD undergo surgery within 6 weeks of completion of NAT followed by SOC adjuvant therapy.

ADJUVANT THERAPY: Within 4-6 weeks of surgery, patients undergo RT once daily, 5 days per week for a total of 30 fractions over 6 weeks and receive cisplatin or carboplatin weekly during RT.

Patients also undergo MRI, PET/CT, CT, and collection of blood samples throughout the trial. Patients may undergo biopsy pre-treatment and/or on study.

After completion of definitive therapy, patients are followed up at 3, 9, 15, 21, and 27 months and then every 12 months for an additional 3 years (5 years total follow up).

Conditions: Sinonasal Squamous Cell Carcinoma, Stage III Sinonasal Cancer AJCC v8, Stage IVA Sinonasal Cancer AJCC v8, Stage IVB Sinonasal Cancer AJCC v8
Being tested: Biopsy Procedure, Biospecimen Collection, Carboplatin, Cemiplimab, Chemoradiotherapy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Biopsy ProcedureProcedure or surgery
Also called Biopsy, BIOPSY_TYPE, Bx
Undergo biopsy
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection
Undergo collection of blood samples
CarboplatinDrug
Also called Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino
Given IV
CarboplatinDrug
Also called Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino
Given carboplatin
CemiplimabBiological
Also called Cemiplimab RWLC, Cemiplimab-rwlc, Libtayo, REGN 2810
Given IV
ChemoradiotherapyOther
Also called Chemoradiation, CRT, CRTx, Radiochemotherapy
Undergo SOC CRT
CisplatinDrug
Also called Abiplatin, Blastolem, Briplatin, CDDP
Given cisplatin
Computed TomographyProcedure or surgery
Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography
Undergo PET/CT and CT
Magnetic Resonance ImagingProcedure or surgery
Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan
Undergo MRI
PaclitaxelDrug
Also called Anzatax, Asotax, Bristaxol, Praxel
Given IV
Positron Emission TomographyProcedure or surgery
Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)
Undergo PET/CT
Radiation TherapyRadiation
Also called Cancer Radiotherapy, Energy Type, ENERGY_TYPE, Irradiate
Undergo radiation therapy
Surgical ProcedureProcedure or surgery
Also called Operation, Surgery, Surgery Type, Surgery, NOS
Undergo surgery

Study groups in NCT07281417
Study group	Role	What they receive
Arm 1 (cemiplimab, carboplatin, paclitaxel)	Experimental	See Detailed Description. Receives: Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Drug: Carboplatin; Biological: Cemiplimab; Other: Chemoradiotherapy; Drug: Cisplatin; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Drug: Paclitaxel; Procedure: Positron Emission Tomography; Radiation: Radiation Therapy; Procedure: Surgical Procedure
Arm 2 (carboplatin, paclitaxel)	Active comparator	See Detailed Description. Receives: Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Drug: Carboplatin; Other: Chemoradiotherapy; Drug: Cisplatin; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Drug: Paclitaxel; Procedure: Positron Emission Tomography; Radiation: Radiation Therapy; Procedure: Surgical Procedure

What is being measured

The primary outcome is the main question the study is designed to answer.

Event free survival (EFS)
Progression will be assessed per Response Evaluation Criteria in Solid Tumors version 1.1. To evaluate EFS, survival functions will be computed using the Kaplan-Meier method and compared between groups using the stratified log-rank test. Adjustment for additional covariates will be performed using Cox proportional hazards regression analysis if numbers allow.
Measured: From randomization to first occurrence of progression of disease or death, assessed up to 5 years

Secondary outcomes (5)

Overall response rate (ORR)
ORR will be defined as complete response + partial response (≥ 30% decrease in tumor volume) per Response Evaluation Criteria in Solid Tumors version 1.1 criteria. ORR will be estimated with a 95% confidence interval using the exact Clopper Pearson method. The ORR will be compared between with neoadjuvant cemiplimab (REGN2810)/carboplatin/paclitaxel (Arm 1) to carboplatin/paclitaxel (Arm 2) using the Cochran-Mantel-Haenszel test, stratified by the same factors used for the primary endpoint. ORR for the aggregate study cohort (Arm 1 + Arm 2) will be compared to historical standard of care using the same analysis plan.
Measured: Up to 5 years
Incidence of adverse events (AEs) associated with neoadjuvant therapy (NAT)
Both acute toxicities and chronic toxicities will be graded by the treating investigator using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. The frequency of participants experiencing a specific AE will be tabulated by dose level, cycle, seriousness, worst severity, timing of occurrence, outcome, and relationship to study drug. In addition, the number and percentage of participants experiencing a specific toxicity will be tabulated similarly. Accrual will be halted if excessive numbers of unacceptable toxicities are observed. This is defined as > 30% grade 4 treatment-related AEs, which are directly attributable to NAT.
Measured: Up to 5 years
Changes in T-cell clonality/diversity
The changes in T-cell clonality/diversity will be assessed using ribonucleic acid sequencing (RNAseq) and correlated with NAT response and EFS. RNAseq data will undergo quality control, alignment to the human reference genome, and transcript quantification using standard bioinformatics pipelines. T-cell receptor sequences will be reconstructed using tools such as MiXCR or TRUST4. Measures of T-cell clonality and diversity (e.g., Shannon entropy, clonality index) will be calculated. Changes in T-cell clonality/diversity pre- and post-treatment will be assessed using paired t-tests or Wilcoxon signed-rank tests. Associations with NAT response and EFS will be analyzed using logistic regression and Cox proportional hazards models, adjusting for relevant covariates. Multiple testing correction using the Benjamini-Hochberg method will be applied where appropriate.
Measured: Up to 5 years
Organ preservation rates
Organ preservation in the post-treatment setting is defined as physical and functional preservation of the organ. For example, orbital preservation would imply maintenance of the entirety of the orbit and preservation of vision and motion. Orbital preservation rates will be summarized using descriptive statistics such as mean, standard deviation, median, and range. At the time of enrollment the treating team, with the guidance of the surgical team, will indicate what major anatomic locations would have to be resected if the patient elected initial primary surgical therapy (palate, orbit, and/or skull base). This prospective information will allow concrete subsequent secondary analyses of organ preservation rates without the bias of outcome or recall.
Measured: Up to 5 years
Overall survival (OS)
The Kaplan-Meier method will be used to estimate OS and 95% confidence intervals will be reported. OS for the aggregate study cohort (Arm 1 + Arm 2) will be compared to historical standard of care using the same analysis plan.
Measured: From the start of NAT to death, assessed up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Sep 202616 Dec 2030

First posted15 Dec 2025
Study start1 Sep 2026
Primary completion16 Dec 2030 (estimated)
Study completion16 Dec 2030 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Sinonasal 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: 108 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT07281417
Sponsor's protocol ID: NCI-2025-09016
Other IDs: NCI-2025-09016, 10721, 10721, UM1CA186712
Status last verified: Sep 2026
First submitted: 12 Dec 2025
Last updated: 5 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.

Interested in taking part?

Each site lists its own contact. Pick the site nearest to you.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See sites and contacts

Active, not recruitingPhase 2/3
Testing the Use of Investigational Drugs Atezolizumab and/or Bevacizumab With or Without Standard Chemotherapy in the Second-Line Treatment of Advanced-Stage Head and Neck Cancers
Clinical Stage IV HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, Metastatic Head and Neck Squamous Cell Carcinoma
RecruitingPhase 1
Testing the Addition of an Anti-Cancer Drug, Camonsertib, to Radiation Therapy for Recurrent Head and Neck Squamous Cell Carcinoma
Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, Recurrent Head and Neck Squamous Cell Carcinoma
Active, not recruitingPhase 3
Chemotherapy With or Without Bevacizumab in Treating Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
Neck Squamous Cell Carcinoma of Unknown Primary, Recurrent Hypopharyngeal Squamous Cell Carcinoma
RecruitingPhase 1
Testing the Addition of Ipatasertib to Usual Chemotherapy and Radiation for Head and Neck Cancer
Clinical Stage II HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8
Active, not recruitingPhase 2
Chemotherapy Before Surgery and Radiation Therapy or Surgery and Radiation Therapy Alone in Treating Patients With Nasal and Paranasal Sinus Cancer That Can Be Removed by Surgery
Stage III Sinonasal Squamous Cell Carcinoma AJCC v6 and v7, Stage IVA Sinonasal Squamous Cell Carcinoma AJCC v7

All Sinonasal Squamous Cell Carcinoma trials

Study at a glance

From the registry record, last updated by the sponsor on 5 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Neoadjuvant Chemotherapy With or Without Cemiplimab (REGN2810) in Sinonasal Squamous Cell Carcinoma: A Randomized Phase 2 Study
ClinicalTrials.gov ID: NCT07281417
Acronym / sponsor ID: NCI-2025-09016
Conditions: Sinonasal Squamous Cell Carcinoma, Stage III Sinonasal Cancer AJCC v8, Stage IVA Sinonasal Cancer AJCC v8, Stage IVB Sinonasal Cancer AJCC v8
Phase: Phase 2
Study type: Interventional
Recruitment status: Recruiting
Enrolment: 108 participants (estimated)
Lead sponsor: National Cancer Institute (NCI)US National Institutes of Health
Study start: 1 Sep 2026 (actual)
Primary completion: 16 Dec 2030 (estimated)
Study completion: 16 Dec 2030 (estimated)
First posted: 15 Dec 2025 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

PRIMARY OBJECTIVE:

To assess whether neoadjuvant therapy (NAT) with cemiplimab (REGN2810)/carboplatin/paclitaxel (Arm 1) results in improved event free survival (EFS) compared to carboplatin/paclitaxel (Arm 2) in participants with sinonasal squamous cell carcinoma (SNSCC).

SECONDARY OBJECTIVES:

To compare objective response rate (ORR) between neoadjuvant cemiplimab (REGN2810)/carboplatin/paclitaxel (Arm 1) and neoadjuvant carboplatin/paclitaxel (Arm 2) and to historical standard of care (SOC) in participants with SNSCC.

II. To compare overall survival (OS) between neoadjuvant cemiplimab (REGN2810)/carboplatin/paclitaxel (Arm 1) and carboplatin/paclitaxel (Arm 2) and to historical SOC in participants with SNSCC.

III. To characterize toxicity with NAT in SNSCC. IV. To measure changes in T-cell clonality/diversity using ribonucleic acid (RNA) sequencing (RNAseq) and correlate with NAT response and EFS.

To evaluate organ preservation (orbital and skull base) rate with NAT in SNSCC.

CORRELATIVE OBJECTIVES:

To correlate human papillomavirus (HPV) status with ORR and OS after NAT. II. To correlate combined positive score (CPS) for PD-L1 expression with OS and EFS.

III. To measure the kinetics of circulating tumor DNA (ctDNA) pre- and post-NAT and correlate with ORR and OS after NAT.

IV. To correlate change in Sinonasal Morbidity Score with ORR and EFS after NAT.

To conduct DNA sequencing on pre-treatment tumor biopsies to determine whether features of the tumor genomic landscape are associated with response to NAT.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM 1:

ARM 2:

DEFINITIVE THERAPY: Patients with CR or PR receive concurrent SOC CRT. Patients with SD or PD undergo surgery within 6 weeks of completion of NAT followed by SOC adjuvant therapy.

ADJUVANT THERAPY: Within 4-6 weeks of surgery, patients undergo RT once daily, 5 days per week for a total of 30 fractions over 6 weeks and receive cisplatin or carboplatin weekly during RT.

Patients also undergo MRI, PET/CT, CT, and collection of blood samples throughout the trial. Patients may undergo biopsy pre-treatment and/or on study.

After completion of definitive therapy, patients are followed up at 3, 9, 15, 21, and 27 months and then every 12 months for an additional 3 years (5 years total follow up).

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Arm 1 (cemiplimab, carboplatin, paclitaxel)	Experimental	Procedure: Biopsy Procedure, Procedure: Biospecimen Collection, Drug: Carboplatin, Biological: Cemiplimab, Other: Chemoradiotherapy, Drug: Cisplatin, Procedure: Computed Tomography, Procedure: Magnetic Resonance Imaging, Drug: Paclitaxel, Procedure: Positron Emission Tomography, Radiation: Radiation Therapy, Procedure: Surgical ProcedureSee Detailed Description.
Arm 2 (carboplatin, paclitaxel)	Active comparator	Procedure: Biopsy Procedure, Procedure: Biospecimen Collection, Drug: Carboplatin, Other: Chemoradiotherapy, Drug: Cisplatin, Procedure: Computed Tomography, Procedure: Magnetic Resonance Imaging, Drug: Paclitaxel, Procedure: Positron Emission Tomography, Radiation: Radiation Therapy, Procedure: Surgical ProcedureSee Detailed Description.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (21 listed)

Patients must have histologically confirmed squamous cell carcinoma of sinonasal origin
Patients must have a T stage (T3, T4a, and select T4b) primary tumor according to American Joint Committee on Cancer (AJCC) 8th edition. 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
No evidence of metastatic disease determined by pre-treatment imaging. Metastatic disease to neck nodes is considered locally advanced and therefore allowable. Patients with N0 and N1-3 disease will be eligible
Known HPV status (i.e., HPV negative, p16 immunohistochemistry [IHC] positive, high risk [HR]-HPV in situ hybridization [ISH] positive) from testing performed prior to referral. HPV status data (e.g., date of test, type of test [p16 IHC or HR-HPV ISH] and testing result) must be collected during enrollment. Patients who do not have this information available for collection will not be enrolled on this study
Age ≥ 18 years

Key exclusion criteria (11 listed)

Patients with unresectable disease
Patients presenting with T3 disease without the need for maxillectomy and/or orbital invasion requiring orbital dissection/resection
Patients who have had any previous systemic therapy to the index lesion in the past 12 months. This includes cemiplimab (REGN2810) and/or other immune modulating agents. Previous systemic therapy may alter or affect response
Patients who had palliative RT (< 20 Gy) within 1 week prior to entering the study
Ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest risk for immune-mediated adverse events (imAEs)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Biopsy ProcedureAlso: Biopsy, BIOPSY_TYPE, BxUndergo biopsy	Procedure or surgery	Arm 1 (cemiplimab, carboplatin, paclitaxel), Arm 2 (carboplatin, paclitaxel)
Biospecimen CollectionAlso: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen CollectionUndergo collection of blood samples	Procedure or surgery	Arm 1 (cemiplimab, carboplatin, paclitaxel), Arm 2 (carboplatin, paclitaxel)
CarboplatinAlso: Blastocarb, Carboplat, Carboplatin Hexal, CarboplatinoGiven IV	Drug	Arm 1 (cemiplimab, carboplatin, paclitaxel), Arm 2 (carboplatin, paclitaxel)
CarboplatinAlso: Blastocarb, Carboplat, Carboplatin Hexal, CarboplatinoGiven carboplatin	Drug	Arm 1 (cemiplimab, carboplatin, paclitaxel), Arm 2 (carboplatin, paclitaxel)
CemiplimabAlso: Cemiplimab RWLC, Cemiplimab-rwlc, Libtayo, REGN 2810Given IV	Biological	Arm 1 (cemiplimab, carboplatin, paclitaxel)
ChemoradiotherapyAlso: Chemoradiation, CRT, CRTx, RadiochemotherapyUndergo SOC CRT	Other	Arm 1 (cemiplimab, carboplatin, paclitaxel), Arm 2 (carboplatin, paclitaxel)
CisplatinAlso: Abiplatin, Blastolem, Briplatin, CDDPGiven cisplatin	Drug	Arm 1 (cemiplimab, carboplatin, paclitaxel), Arm 2 (carboplatin, paclitaxel)
Computed TomographyAlso: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial TomographyUndergo PET/CT and CT	Procedure or surgery	Arm 1 (cemiplimab, carboplatin, paclitaxel), Arm 2 (carboplatin, paclitaxel)
Magnetic Resonance ImagingAlso: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging ScanUndergo MRI	Procedure or surgery	Arm 1 (cemiplimab, carboplatin, paclitaxel), Arm 2 (carboplatin, paclitaxel)
PaclitaxelAlso: Anzatax, Asotax, Bristaxol, PraxelGiven IV	Drug	Arm 1 (cemiplimab, carboplatin, paclitaxel), Arm 2 (carboplatin, paclitaxel)
Positron Emission TomographyAlso: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)Undergo PET/CT	Procedure or surgery	Arm 1 (cemiplimab, carboplatin, paclitaxel), Arm 2 (carboplatin, paclitaxel)
Radiation TherapyAlso: Cancer Radiotherapy, Energy Type, ENERGY_TYPE, IrradiateUndergo radiation therapy	Radiation	Arm 1 (cemiplimab, carboplatin, paclitaxel), Arm 2 (carboplatin, paclitaxel)
Surgical ProcedureAlso: Operation, Surgery, Surgery Type, Surgery, NOSUndergo surgery	Procedure or surgery	Arm 1 (cemiplimab, carboplatin, paclitaxel), Arm 2 (carboplatin, paclitaxel)

Primary outcome

Event free survival (EFS)
Time frame: From randomization to first occurrence of progression of disease or death, assessed up to 5 years
Progression will be assessed per Response Evaluation Criteria in Solid Tumors version 1.1. To evaluate EFS, survival functions will be computed using the Kaplan-Meier method and compared between groups using the stratified log-rank test. Adjustment for additional covariates will be performed using Cox proportional hazards regression analysis if numbers allow.

5 secondary outcomes

Overall response rate (ORR)
Time frame: Up to 5 years
Incidence of adverse events (AEs) associated with neoadjuvant therapy (NAT)
Time frame: Up to 5 years
Changes in T-cell clonality/diversity
Time frame: Up to 5 years
Organ preservation rates
Time frame: Up to 5 years
Overall survival (OS)
Time frame: From the start of NAT to death, assessed up to 5 years

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Oct 2026.
Individual participant dataSharing planned: 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.

UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care

Irvine, United States

877-827-8839

ucstudy@uci.edu

USC / Norris Comprehensive Cancer Center

Los Angeles, United States

323-865-0451

UC Irvine Health/Chao Family Comprehensive Cancer Center

Orange, United States

877-827-8839

ucstudy@uci.edu

Siddharth Sheth principal investigator

Ohio State University Comprehensive Cancer Center LAO

18 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 5 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 18 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Event free survival (EFS) (time frame: From randomization to first occurrence of progression of disease or death, assessed up to 5 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07281417.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Oct 2026.