Summary

This phase I trial studies how well cemiplimab before and after surgery works in treating patients with high risk cutaneous squamous cell cancer. 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. Giving cemiplimab before surgery may improve risk of the cancer returning in patients with high risk cutaneous squamous cell cancer.

Objectives

PRIMARY OBJECTIVE:
I. To establish the pathologic response rate of neoadjuvant cemiplimab in cutaneous squamous cell carcinoma (cSCC).

SECONDARY OBJECTIVES:
I. To document the local recurrence rate of high-risk cSCC treated with adjuvant cemiplimab.
II. To document the systemic recurrence rate of high-risk cSCC treated with adjuvant cemiplimab.
III. To document the 6-month, 12-month, 2-year overall survival (OS), recurrence-free survival (RFS) for patients with high risk cSCC.

TERTIARY/EXPLORATORY OBJECTIVE:
I. To evaluate the immune profile of fresh tumor tissue, blood in patients with cSCC treated with cemiplimab.

OUTLINE:

NEOADJUVANT PHASE: Prior to standard of care surgery, patients receive cemiplimab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT or MRI within 7 days of surgery.

ADJUVANT PHASE: Within 2-6 weeks after completion of standard of care radiation therapy (or surgery if no radiation therapy), patients receive cemiplimab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 18 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT or MRI every 3 months following cycle 4 until the end of treatment.

After completion of study treatment, patients are followed up every 12 weeks for 2 years, every 6 months for the next 3 years, and then annually for up to 10 years.

Eligibility

1. Must be at least >= 18 years of age
2. Patient must have a known diagnosis of high risk cSCC defined by the following criteria: * Nodal disease with extracapsular extension (ECE) and at least one node >= 20 mm on the surgical pathology report * In-transit metastases (ITM) defined as skin or subcutaneous metastases that are > 2 cm from the primary lesion but are not beyond the regional nodal basin * T4 lesion for head and neck CSCC * Perineural invasion (PNI), defined as clinical and/or radiologic involvement of named nerves * Recurrent CSCC, defined as CSCC that arises within the area of the previously resected tumor or at least one of the following additional features: ** >= N2b disease associated with the recurrent lesion ** Nominal >= T3 (recurrent lesion >= 4 cm in diameter or minor bone erosion or deep invasion > 6 mm measured from the granular layer of normal adjacent epithelium) ** Poorly differentiated histology and >= 20 mm diameter of recurrent lesion. The recurrent lesion must be documented to be within the area of the previously resected CSCC by radial measurement of the greatest radius of the final defect, measured from the estimated center of the original surgical wound
3. Cancer confirmed to be surgically resectable, with surgery evaluation with planned prior to resection
4. No prior systemic immunotherapy, no prior anti-PD1 therapy
5. Eastern Cooperative Oncology Group (ECOG) performance status =< 1
6. Hemoglobin >= 9.0 g/dl (within 28 days of cycle 1 day 1)
7. Absolute neutrophil count (ANC) >= 1,500/mcL (within 28 days of cycle 1 day 1)
8. Platelets >= 100,000/mcL (within 28 days of cycle 1 day 1)
9. Total bilirubin =<1.5 institutional upper limit of normal (ULN) (within 28 days of cycle 1 day 1)
10. Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 institutional upper limit of normal (ULN) (within 28 days of cycle 1 day 1)
11. Albumin >= 3.0 g/dL (within 28 days of cycle 1 day 1)
12. Serum creatinine =< 1.5 x ULN (or calculated creatinine clearance of >= 50 mL/min using Cockcroft-Gault formula) (within 28 days of cycle 1 day 1)
13. International normalized ratio (INR) =< 1.5 (within 28 days of cycle 1 day 1) * Anticoagulation is allowed only with low molecular weight heparin (LMWH). Patient receiving LMW heparin on stable therapeutic dose for more than 2 weeks or with factor Xa level < 1.1U/mL are allowed on the trial
14. Clinically significant toxic effect(s) of the most recent prior anti-cancer therapy must be grade 1 or resolved (except alopecia and sensory neuropathy); patients with grade 2 adrenal insufficiency related to prior anti-cancer therapy (defined as requiring medical intervention, such as concomitant steroids) or grade 2 hypothyroidism (defined as requiring hormone replacement therapy) may be enrolled provided that clinical symptoms are adequately controlled and the daily dose is 10 mg or less of prednisone or equivalent. If the patient received major surgery or radiation therapy of > 30 Gy, they must have recovered from the toxicity and/or complications from the intervention
15. 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
16. The effects of cemiplimab on the developing human fetus are unknown. For this reason female of child-bearing potential (FCBP) must have a negative serum or urine pregnancy test prior to starting therapy
17. FCBP and men must agree to use adequate contraception (at least one highly effective method and one additional method of birth control at the same time or complete abstinence) prior to study entry, for the duration of study participation and for at least 6 months following study drug discontinuation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. A female of childbearing potential (FCBP) is a sexually mature woman who: has not undergone a hysterectomy or bilateral oophorectomy or has not been naturally postmenopausal for at least 12 consecutive months (if age >= 55 years); if the female subject is < 55 years and she has been naturally postmenopausal for >= 1 year her reproductive status has to be verified by additional lab tests (< 20 estradiol OR estradiol < 40 with follicle stimulating hormone [FSH] > 40 in women not on estrogen replacement therapy)
18. Patients must agree not to donate blood, sperm/ova while taking protocol therapy and for at least 6 months after stopping treatment
19. Willingness and ability of the subject to comply with scheduled visits, drug administration plan, protocol-specified laboratory tests, other study procedures, and study restrictions
20. Evidence of a personally signed informed consent indicating that the subject is aware of the neoplastic nature of the disease and has been informed of the procedures to be followed, the experimental nature of the therapy, alternatives, potential risks and discomforts, potential benefits, and other pertinent aspects of study participation