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