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

Plain English Summary

Testing the Addition of Cemiplimab (REGN2810) to Chemotherapy Treatment Given Prior to Surgery in Patients With Sinonasal Squamous Cell Carcinoma is a Phase 2 clinical trial sponsored by National Cancer Institute (NCI) studying Sinonasal Squamous Cell Carcinoma, Stage III Sinonasal Cancer AJCC v8, Stage IVA Sinonasal Cancer AJCC v8, Stage IVB Sinonasal Cancer AJCC v8. Tests if adding cemiplimab to chemotherapy before surgery can stop cancer from growing or spreading better than chemotherapy alone. For patients with sinonasal squamous cell carcinoma, stages III to IVB, who are fit for surgery and chemotherapy. Participation involves taking carboplatin and paclitaxel, and possibly cemiplimab, before surgery, with regular check-ups. Alternative treatments include surgery followed by radiation, with or without chemotherapy. The trial aims to enroll 108 participants.

Official Summary

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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Eligible if over 18, with sinonasal squamous cell carcinoma, no metastasis, and fit for chemotherapy. Not eligible if under 18, with unresectable disease, or with significant autoimmune disease. Age: 18 years and older. Health: Must be fit for chemotherapy and have no significant health issues. This trial is studying Sinonasal Squamous Cell Carcinoma, Stage III Sinonasal Cancer AJCC v8, Stage IVA Sinonasal Cancer AJCC v8, Stage IVB Sinonasal Cancer AJCC v8, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome measures how long patients can stay free from cancer progression or death after treatment. The specific primary outcome measures are: Event free survival (EFS) (From randomization to first occurrence of progression of disease or death, assessed up to 5 years). 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 improve treatment outcomes for sinonasal squamous cell carcinoma by combining chemotherapy with immunotherapy. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Sinonasal Squamous Cell Carcinoma, Stage III Sinonasal Cancer AJCC v8, Stage IVA Sinonasal Cancer AJCC v8, Stage IVB Sinonasal Cancer AJCC v8, where improved treatment options are needed.

Investor Insight

The market for innovative cancer treatments is large, with a competitive landscape, and there is a high probability of approval given the unmet need. 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 have sinonasal squamous cell carcinoma and are fit for surgery and chemotherapy. Participation involves taking medication and having regular check-ups. This trial is currently recruiting participants. The trial is being conducted at 1 site. 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: 108 participants

Interventions

• PROCEDURE: Biopsy Procedure — Undergo biopsy
• PROCEDURE: Biospecimen Collection — Undergo collection of blood samples
• DRUG: Carboplatin — Given IV
• DRUG: Carboplatin — Given carboplatin
• BIOLOGICAL: Cemiplimab — Given IV

Primary Outcomes

• Event free survival (EFS) (From randomization to first occurrence of progression of disease or death, assessed up to 5 years)

Secondary Outcomes

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

Full Eligibility Criteria

Inclusion Criteria:

* 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
* 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

Exclusion Criteria:

* 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
* Patients who have not recovered from adverse 

Trial Locations

• Ohio State University Comprehensive Cancer Center LAO, Columbus, Ohio, United States

Frequently Asked Questions

Related Conditions

• Sinonasal Squamous Cell Carcinoma
• Head and Neck Cancer
• Squamous Cell Carcinoma
• Cancer Immunotherapy
• Neoadjuvant Therapy
• Chemotherapy
• Surgery
• Radiation Therapy
• Immunotherapy
• Cancer Treatment

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