Cemiplimab Plus Fianlimab for the Treatment of Locally Advanced Head and Neck Basal Cell Carcinoma Before Surgery

Neoadjuvant REGN2810 (Cemiplimab) or REGN2810 (Cemiplimab) Plus REGN3767 (Fianlimab) in Cutaneous Basal Cell Carcinoma of the Head and Neck

A non-randomized two-cohort study of neoadjuvant Cemiplimab or neoadjuvant Cemiplimab plus Fianlimab (CF) in patients with basal cell carcinoma of the head and neck. Enrollment in the dual-therapy cohort will begin after completion of enrollment in the monotherapy cohort. Patients will undergo at least 2 and up to 6 infusions of immunotherapy prior to surgical resection. If patients have progression on neoadjuvant treatment, they may switch to standard of care surgical resection or hedgehog inhibitors prior to surgery. The primary endpoints are objective response rate and disease control rate. Safety and surgical benefit rate (de-escalation of surgery) with preservation of key anatomic structures are secondary endpoints. Correlative endpoints include analysis of pre and post treatment primary tumor and blood samples compared for histology, tumor genetics and immune cell composition.

Study Overview

• Status: Recruiting
• Conditions: Basal Cell Carcinoma; Locally Advanced Basal Cell Carcinoma
• Intervention / Treatment: Other: Quality-of-Life Assessment; Procedure: Biospecimen Collection; Procedure: Magnetic Resonance Imaging; Procedure: Biopsy; Procedure: Computed Tomography; Biological: Cemiplimab; Biological: Fianlimab

Detailed Description

The proposed study is a phase II trial of neoadjuvant Cemiplimab (cohort 1) or Cemiplimab plus Fianlimab (cohort 2) that will target patients with advanced BCCHN who have not been previously treated with anti-PD1 checkpoint therapy for this primary lesion. Patients will be assessed by the enrolling surgeon for response to therapy every 3 weeks (before initiating the next cycle) by clinical assessment, and by imaging assessment (every 6 weeks). Patients will undergo a minimum of 2 cycles of therapy over a 6-week window prior to surgery. Patients who demonstrate clinical or RECISTv1.1 response or stable disease with regression or up to 5% growth, will go on to the next cycle of treatment. Patients who demonstrate clinical or RECISTv1.1 radiographic progression or stable disease with >5%-20% growth will proceed directly to surgery or to other SOC therapy (after biopsies) (Fig 1). Patients who demonstrate a complete clinical response prior to at any assessment prior to completion of 6 cycles will proceed to appropriate surgery or biopsy of tumor site to ensure complete pathologic response at the time of CR.

PRIMARY OBJECTIVE:

I. Our primary objective is to assess treatment response of locally advanced BCC of the head and neck (BCCHN) in the neoadjuvant, presurgical setting.

SECONDARY OBJECTIVES:

I. To assess functional organ preservation with neoadjuvant Cemiplimab or Cemiplimab plus Fianlimab therapy.

II. To assess pathologic response. III. To assess safety of neoadjuvant therapy. IV. To assess changes in quality of life.

EXPLORATORY OBJECTIVE:

I. To assess treatment-related changes in the immune microenvironment related to functional changes in immune cell composition.

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Joseph Curry, MD; Phone Number: 215-955-6760; Email: Joseph.Curry@jefferson.edu

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • Recruiting
      • University of Miami Health System
      • Contact: Donald Weed, MD
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Recruiting
      • Thomas Jefferson University Hospital
      • Contact: Joseph Curry, MD; Phone Number: 215-955-6760; Email: Joseph.Curry@jefferson.edu
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Recruiting
      • Vanderbilt University
      • Contact: Michael Topf, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

-Individuals must meet all of the following inclusion criteria in order to be eligible to participate in the study:

1. Pathologically confirmed, locally-advanced BCC of the head and neck of any stage which is not resectable without major morbidity or unresectable, defined as requiring greater than 30% auriculectomy, rhinectomy, upper or lower lip resection, orbital exenteration (due to lid or orbital involvement), facial nerve sacrifice, or any Brigham and Women's stage 2b or 3 disease of head and neck (see Table 5).
2. Male or female, aged ≥18 years of age
3. Performance status 0-1.
4. Must have a life expectancy of at least 6 months as judged by the treating physician.

5. Adequate organ function:

   1. Absolute neutrophil count 1500/μl or more;
   2. Platelets 100,000/μl or more,
   3. Hemoglobin 9 g/dl or more;
   4. Bilirubin less than or equal to 1.5 x the upper limit of normal (except subjects with Gilbert syndrome, who can have total bilirubin <3 mg/dl);
   5. AST and ALT less than or equal to 2.5 x the upper limit of normal,
   6. GFR greater than or equal to 40 ml/min using the Cockcroft-Gault formula or measured creatinine clearance using 24 hours urine collection
6. Women of reproductive potential should have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG), which must also be confirmed as negative within 28 days of the start of study drugs.
7. Women of reproductive potential must use highly effective contraception methods to avoid pregnancy for 120 days after the last dose of study drugs. "Women of reproductive potential" is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes. In addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU/mL.
8. Men of reproductive potential who are sexually active with women of reproductive potential must use any contraceptive method with a failure rate of less than 1% per year. Men who are receiving the study medications will be instructed to adhere to contraception for 120 days after the last dose of study drugs. Men who are azoospermic do not require contraception.
9. Informed Consent: All subjects must be able to comprehend and sign a written informed consent document.

Exclusion Criteria:

An individual who meets any of the following criteria will be excluded from participation in this study:

1. Prior radiation therapy within the past 6 months for this target cancer documented by surgeon at Visit 1, Day 0 initial assessment. (Prior surgical resection to area/tumor is acceptable.)
2. Any history of allergy to the study drug components.
3. Any concurrent malignancies: exceptions include- basal cell carcinoma of the skin at another site, chronic lymphocytic leukemia, melanoma in situ, squamous cell carcinoma of the skin of a secondary location, superficial bladder cancer or in situ cervical cancer that has undergone potentially curative therapy. Patients with a history of other prior malignancy must have been treated with curative intent and must have remained disease-free for 2 years post-diagnosis.
4. Any unresolved toxicity NCI CTCAE v 5.0 Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria. Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician. Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with anti-PD1 therapy may be included only after consultation with the Study Physician.
5. Any Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 28 days of study drug administration., or a prior history of allogenic organ transplantation.
6. Any diagnosis of a significant connective tissue disorder as determined by the treating surgeon or medical team.
7. Patients must not be receiving any other investigational agents.
8. Receipt of a live attenuated vaccine within 30 days prior to the first dose of drug on trial.
9. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.
10. Patients must not be pregnant or breastfeeding.
11. Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc]and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV)antibody are eligible only if polymerase chain reaction is negative for HCVRNA.
12. Any patient with prior immunotherapy or HHI for malignancy treatment.
13. Any untreated metastasis(es) to the brain that may be considered active.
14. History of pneumonitis with the past 5 years.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: Cemiplimab; Patients will undergo 2 infusions of Cemiplimab (Cemi), 350 mg every 3 weeks. Patients undergo CT or MRI scans and collection of blood samples throughout the trial. Patients also undergo biopsies during screening and on study. The recommended dose of Cemiplimab is 350 mg as an intravenous infusion over 30 minutes every 3 weeks (constituting one cycle). Dosing will occur in this manner for a single dose of 350mg Cemiplimab every 3 weeks constituting 1 cycle of therapy. Patients will undergo at least 2 cycles of Cemiplimab and at most, 4 additional cycles dependent upon treatment response.	Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Procedure: Biospecimen Collection; Undergo collection of blood samples; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Procedure: Magnetic Resonance Imaging; Undergo MRI; Other Names: MRI; Magnetic Resonance; Magnetic Resonance Imaging Scan; MR; MR Imaging; MRI Scan; NMR Imaging; NMRI; Medical Imaging; Magnetic Resonance / Nuclear Magnetic Resonance; nuclear magnetic resonance imaging; Magnetic Resonance Imaging (MRI); sMRI; Magnetic resonance imaging (procedure); MRIs; Structural MRI; Procedure: Biopsy; Undergo biopsy; Other Names: Bx; BIOPSY_TYPE; Procedure: Computed Tomography; Undergo CT scan; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Tomography; tomography; CT SCAN; computerized axial tomography; Biological: Cemiplimab; Given IV; Other Names: REGN2810; Cemiplimab RWLC; Cemiplimab-rwlc; Libtayo; Immunoglobulin G4; Dimer; 1801342-60-8; Anti-(Human Programmed Cell Death Protein 1) (Human Monoclonal REGN2810 Heavy Chain); Disulfide with Human Monoclonal REGN2810 kappa-chain
Experimental: Cohort 2: Fianlimab + Cemiplimab; Patients will undergo infusions of Cemiplimab (C) and Fianlimab (F), 350 mg Cemiplimab + 1600 mg Fianlimab every 3 weeks. Fianlimab in combination with cemiplimab can be administered to patients in a sequential order through co-administration, or concurrently via a fixed-dose combination (FDC). When the FDC is used, the drug product containing co-formulated drugs in a vial is injected into the IV bag and delivered intravenously to the patient. FDC of fianlimab 1600 mg + cemiplimab 350 mg will be administered as a single infusion over 30 to 40 minutes every 3 weeks (constituting one cycle). Patients will undergo at least 2 cycles of the FDC and at most, 4 additional cycles dependent upon treatment response.	Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Procedure: Biospecimen Collection; Undergo collection of blood samples; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Procedure: Magnetic Resonance Imaging; Undergo MRI; Other Names: MRI; Magnetic Resonance; Magnetic Resonance Imaging Scan; MR; MR Imaging; MRI Scan; NMR Imaging; NMRI; Medical Imaging; Magnetic Resonance / Nuclear Magnetic Resonance; nuclear magnetic resonance imaging; Magnetic Resonance Imaging (MRI); sMRI; Magnetic resonance imaging (procedure); MRIs; Structural MRI; Procedure: Biopsy; Undergo biopsy; Other Names: Bx; BIOPSY_TYPE; Procedure: Computed Tomography; Undergo CT scan; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Tomography; tomography; CT SCAN; computerized axial tomography; Biological: Cemiplimab; Given IV; Other Names: REGN2810; Cemiplimab RWLC; Cemiplimab-rwlc; Libtayo; Immunoglobulin G4; Dimer; 1801342-60-8; Anti-(Human Programmed Cell Death Protein 1) (Human Monoclonal REGN2810 Heavy Chain); Disulfide with Human Monoclonal REGN2810 kappa-chain; Biological: Fianlimab; Fianlimab (REGN3767) administered intravenously in combination with Cemiplimab.; Other Names: REGN3767; Anti-LAG-3 MoAb

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	Defined by responders at surgery using clinical assessment and RECIST v1.1. Results will be summarized with frequency counts, percentages, and exact Clopper-Pearson 95% CIs. Tumor response will follow RECIST v1.1: up to five target lesions (max two per organ) measured by longest diameter (non-nodal) or short axis (nodal). Complete Response is disappearance of all target lesions and lymph nodes <10 mm. Partial Response is ≥30% decrease from baseline. Progressive Disease is ≥20% increase (and ≥5 mm growth) from the smallest on-study sum or the appearance of new lesions. Stable Disease applies when changes do not meet PR or PD. Reasons for unevaluable cases will be documented.	Up to 6 months post surgery (up to Day 309 +/- 3 days)
Disease control rate (DCR)	Defined responders plus stable disease using clinical assessment and RECIST v1.1. Results will be summarized by frequency counts, percentages, and exact Clopper-Pearson 95% CIs. Tumor response will follow RECIST v1.1: up to five target lesions (no more than two per organ) measured by longest diameter (non-nodal) or short axis (nodal). Complete Response is disappearance of all target lesions and lymph nodes <10 mm. Partial Response is ≥30% decrease from baseline. Progressive Disease is ≥20% increase (and ≥5 mm growth) from the smallest on-study sum or new lesions. Stable Disease applies when changes do not meet PR or PD. Reasons for unevaluable cases will be documented.	Up to 6 months post surgery (up to Day 309 +/- 3 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Surgical/Clinical Benefit Rate (SBR)	Percentage of patients with an organ at risk demonstrating tumor response allowing functional organ preservation surgery.	At surgery (Day 129 +/- 3 days)
Pathologic complete response (pCR)	Pathologic complete response (pCR)	Up to 6 months post surgery (up to Day 309 +/- 3 days)
Major pathologic response (mPR)	Major pathologic response (mPR)	Up to 6 months post surgery (up to Day 309 +/- 3 days)
Changes in quality of life and functional organ preservation (FACE-Q)	Assessed by the Functional Assessment of Cancer Therapy Questionnaire (FACE-Q), validated questionnaires. Score range: 0-100, generally higher scores reflect a better outcome. Summarized with descriptive statistics and plotted graphically (i.e., with box plots). Those data will be modeled using generalized linear modeling to account for the correlation of the longitudinal observations from the same patient.	At baseline (Day 1)
Changes in quality of life and functional organ preservation (VFQ-25)	Assessed by the Visual Function Questionnaire (VFQ-25) validated questionnaires. Score range: 0-100, higher scores reflect a better outcome. Summarized with descriptive statistics and plotted graphically (i.e., with box plots). Those data will be modeled using generalized linear modeling to account for the correlation of the longitudinal observations from the same patient.	At baseline (Day 1)
Changes in quality of life and functional organ preservation (FHNSI)	Assessed by the Functional Assessment of Cancer Therapy - Head and Neck Symptom Index (FHNSI) validated questionnaires. Score range: 0-40, higher scores reflect a better outcome. Summarized with descriptive statistics and plotted graphically (i.e., with box plots). Those data will be modeled using generalized linear modeling to account for the correlation of the longitudinal observations from the same patient.	6 months post-surgery (up to Day 309 +/- 3 days)
Changes in quality of life and functional organ preservation (FACE-Q)	Assessed by the Functional Assessment of Cancer Therapy Questionnaire (FACE-Q), validated questionnaires. Score range: 0-100, generally higher scores reflect a better outcome. Summarized with descriptive statistics and plotted graphically (i.e., with box plots). Those data will be modeled using generalized linear modeling to account for the correlation of the longitudinal observations from the same patient.	6 months post-surgery (up to Day 309 +/- 3 days)
Changes in quality of life and functional organ preservation (VFQ-25)	Assessed by the Visual Function Questionnaire (VFQ-25) validated questionnaires. Score range: 0-100, higher scores reflect a better outcome. Summarized with descriptive statistics and plotted graphically (i.e., with box plots). Those data will be modeled using generalized linear modeling to account for the correlation of the longitudinal observations from the same patient.	6 months post-surgery (up to Day 309 +/- 3 days)
Changes in quality of life and functional organ preservation (FHNSI)	Assessed by the Functional Assessment of Cancer Therapy - Head and Neck Symptom Index (FHNSI), FACE-Questionnaire (Q), Visual Function Questionnaire (VFQ)-25 validated questionnaires. Summarized with descriptive statistics and plotted graphically (i.e., with box plots). Those data will be modeled using generalized linear modeling to account for the correlation of the longitudinal observations from the same patient.	At baseline (Day 1) to 6 months post-surgery (up to Day 309 +/- 3 days)
Number of adverse events	Safety and tolerability assessed using CTCAE v5.0.	Up to 6 months post surgery (up to Day 309 +/- 3 days)

Collaborators and Investigators

• Sponsor: Thomas Jefferson University
• Collaborators: Regeneron Pharmaceuticals
• Investigators: Principal Investigator: Joseph Curry, MD, Thomas Jefferson University

Study record dates

Study Major Dates

• Study Start (Actual): July 5, 2023
• Primary Completion (Estimated): July 5, 2031
• Study Completion (Estimated): July 5, 2031

Study Registration Dates

• First Submitted: February 7, 2023
• First Submitted That Met QC Criteria: June 28, 2023
• First Posted (Actual): July 3, 2023

Study Record Updates

• Last Update Posted (Actual): March 24, 2026
• Last Update Submitted That Met QC Criteria: March 19, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Carcinoma; Neoplasms, Basal Cell; Carcinoma, Basal Cell; Amino Acids, Peptides, and Proteins; Proteins; Sulfur Compounds; Organic Chemicals; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Surgical Procedures, Operative; Cytological Techniques; Cytodiagnosis; Physical Phenomena; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Inorganic Chemicals; Diagnostic Techniques, Surgical; Chemistry Techniques, Analytical; Spectrum Analysis; Immunoglobulin Isotypes; Sulfides; Anions; Ions; Electrolytes; Hydrogen Sulfide; Electromagnetic Phenomena; Magnetic Phenomena; Electromagnetic Radiation; Radiation; Radiation, Ionizing; Immunoglobulin G; Biopsy; Specimen Handling; Magnetic Resonance Spectroscopy; Disulfides; X-Rays; cemiplimab
• Other Study ID Numbers: iRISID-2022-0944; JT 24369 (Other Identifier: JeffTrial Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No