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
2 other identifiers
interventional
70
1 country
3
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Jul 2023
Longer than P75 for phase_2
3 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 7, 2023
CompletedFirst Posted
Study publicly available on registry
July 3, 2023
CompletedStudy Start
First participant enrolled
July 5, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 5, 2031
ExpectedStudy Completion
Last participant's last visit for all outcomes
July 5, 2031
March 24, 2026
March 1, 2026
8 years
February 7, 2023
March 19, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
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 Outcomes (10)
Surgical/Clinical Benefit Rate (SBR)
At surgery (Day 129 +/- 3 days)
Pathologic complete response (pCR)
Up to 6 months post surgery (up to Day 309 +/- 3 days)
Major pathologic response (mPR)
Up to 6 months post surgery (up to Day 309 +/- 3 days)
Number of adverse events
Up to 6 months post surgery (up to Day 309 +/- 3 days)
Changes in quality of life and functional organ preservation (FHNSI)
At baseline (Day 1) to 6 months post-surgery (up to Day 309 +/- 3 days)
- +5 more secondary outcomes
Study Arms (2)
Cohort 1: Cemiplimab
EXPERIMENTALPatients 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.
Cohort 2: Fianlimab + Cemiplimab
EXPERIMENTALPatients 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.
Interventions
Given IV
Undergo CT scan
Undergo biopsy
Undergo collection of blood samples
Ancillary studies
Undergo MRI
Fianlimab (REGN3767) administered intravenously in combination with Cemiplimab.
Eligibility Criteria
You may qualify if:
- 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).
- Male or female, aged ≥18 years of age
- Performance status 0-1.
- Must have a life expectancy of at least 6 months as judged by the treating physician.
- Adequate organ function:
- Absolute neutrophil count 1500/μl or more;
- Platelets 100,000/μl or more,
- Hemoglobin 9 g/dl or more;
- 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);
- AST and ALT less than or equal to 2.5 x the upper limit of normal,
- GFR greater than or equal to 40 ml/min using the Cockcroft-Gault formula or measured creatinine clearance using 24 hours urine collection
- 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.
- 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.
- 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.
- Informed Consent: All subjects must be able to comprehend and sign a written informed consent document.
You may not qualify if:
- An individual who meets any of the following criteria will be excluded from participation in this study:
- 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.)
- Any history of allergy to the study drug components.
- 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.
- 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.
- Any diagnosis of a significant connective tissue disorder as determined by the treating surgeon or medical team.
- Patients must not be receiving any other investigational agents.
- Receipt of a live attenuated vaccine within 30 days prior to the first dose of drug on trial.
- 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.
- Patients must not be pregnant or breastfeeding.
- 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.
- Any patient with prior immunotherapy or HHI for malignancy treatment.
- Any untreated metastasis(es) to the brain that may be considered active.
- History of pneumonitis with the past 5 years.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Thomas Jefferson Universitylead
- Regeneron Pharmaceuticalscollaborator
Study Sites (3)
University of Miami Health System
Miami, Florida, 33136, United States
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107, United States
Vanderbilt University
Nashville, Tennessee, 37232, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Joseph Curry, MD
Thomas Jefferson University
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 7, 2023
First Posted
July 3, 2023
Study Start
July 5, 2023
Primary Completion (Estimated)
July 5, 2031
Study Completion (Estimated)
July 5, 2031
Last Updated
March 24, 2026
Record last verified: 2026-03