A PD-1 Checkpoint Inhibitor (Cemiplimab) for High-Risk Localized Locally Recurrent or Regionally Advanced Skin Cancer

  • End date
    Jan 17, 2023
  • participants needed
  • sponsor
    University of Southern California
Updated on 25 October 2021


This phase II trial studies how well cemiplimab before surgery works in treating patients with skin cancer that is high-risk and has not spread to other parts of the body (localized), has come back locally (locally recurrent), or has spread regionally (regionally advanced), and can be removed by surgery (resectable). 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.



I. To assess the pathological partial response (PPR) rate in patients with potentially resectable cutaneous squamous cell carcinoma (CSCC) treated with neoadjuvant cemiplimab.


I. To estimate the pathological complete response rate (PCR). II. To estimate the Response Evaluation Criteria in Solid Tumors (RECIST) (version [v]1.1) 9 week objective response rate (ORR).

III. To estimate the RECIST (v1.1) 12 month progression free (PFS). IV. To assess the toxicity among patients with CSCC treated with neoadjuvant cemiplimab.


I. To evaluate tumor mutational burden (TMB) and correlate with response to PD-1 blockade therapy.

II. To evaluate PD-L1 expression on CSCC tumor cells and correlate with response to PD-1 blockade.

III. To evaluate CD8+ T cell infiltration into CSCC tumors and correlate with response to PD-1 blockade.

IV. To assess other adaptive immune resistance mechanisms in CSCC tumors.


Patients receive cemiplimab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 21 days for up to 3 cycles (or up to 4 cycles for patients whose disease is unresectable after 3 cycles) in the absence of disease progression or unacceptable toxicity. Within 6 weeks of last dose of therapy, patients with potentially resectable tumors undergo surgical resection.

After completion of study treatment, patients are followed up every 3 months for 24 months.

Condition Recurrent Skin Squamous Cell Carcinoma, Stage I Skin Cancer, Stage III Skin Cancer, Stage II Skin Cancer, Resectable Skin Squamous Cell Carcinoma
Treatment Resection, Cemiplimab
Clinical Study IdentifierNCT04315701
SponsorUniversity of Southern California
Last Modified on25 October 2021


Yes No Not Sure

Inclusion Criteria

Histologically confirmed, cutaneous squamous cell carcinoma
Patients must have disease that is deemed potentially resectable, at the time of the start of study, by the treating investigator. The decision to perform surgery on patients must be based on good clinical judgment. Eligible patients for surgical resection must have disease that, in the judgment of the surgeon, is deemed potentially resectable, resulting in free surgical margins
Patients must have measurable disease
Patients must have disease that is considered either: (1) high-risk localized CSCC, (2) locally recurrent CSCC, or (3) regionally advanced CSCC. The criteria specific to each of these populations is listed below
For patients with high-risk localized CSCC, at least two of the following clinical or pathologic high-risk features must be present to be eligible
Clinical risk factors
Any tumor size > 2.0 cm in diameter
Tumors > 1.0 cm in high risk locations, including "mask areas" (central face, eyelids, eyebrow, nose, lips [cutaneous], periorbital, chin, mandible, preauricular and postauricular skin/sulci, genitalia, hands, feet, cheek, forehead, scalp, neck and pretibial)
Any rapidly growing and/or symptomatic tumor
Pathologic risk factors
Poorly differentiated histology
Depth > 6 mm in thickness
Acantholytic / adenoid, adenosquamous, desmoplastic, or metaplastic / carcinosarcomatous histologic subtypes
Invasion beyond subcutaneous fat
Perineural, lymphatic, or vascular involvement
Patients with locally recurrent CSCC, that failed prior surgery, radiation or systemic therapy, are eligible, as long as they have measurable disease and are deemed potentially resectable by the treating investigator
Patients with regionally advanced CSCC, including in-transit, cutaneous, subcutaneous or lymph node metastases are eligible, as long as they have measurable disease and are deemed potentially resectable by the treating investigator
Eastern Cooperative Oncology Group (ECOG) performance status 0-1
Absolute neutrophil count >= 1,000 /mcL
Absolute lymphocyte count >= 500 / mcL
Hemoglobin >= 8.0 g/dL
Platelets >= 75,000/mcl
Total bilirubin =< 1.5 x institutional upper limit of normal
Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SPGT]) =< 3 x institutional upper limit of normal
Creatinine =< 1.8 mg/dl
Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria
Has not undergone a hysterectomy or bilateral oophorectomy; or
Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)
Ability to understand and the willingness to sign a written informed consent and comply with surgical resection at end of study and other study-related procedures

Exclusion Criteria

Metastatic disease that is unresectable. Patients with visceral metastases are not eligible. Regionally advanced disease, including in-transit, cutaneous, subcutaneous, or nodal metastases are allowed, if deemed potentially resectable by the investigator
Prior treatment with cemiplimab or any other agent that blocks the PD-1 or PD-L1 pathway
Prior treatment with other immune modulating agents within fewer than 4 weeks, prior to the first dose of cemiplimab. Examples of immune modulating agents include blockers of CTLA-4, 4-1BB, OX-40, therapeutic vaccines, or cytokine therapies
Patients must not be receiving other concomitant biologic therapy, hormonal therapy, chemotherapy, other anti-cancer therapy or any other investigational agents while on this protocol
Radiation therapy, non-cytotoxic agents or investigational agents in the 4 weeks prior to registration
Immunosuppressive systemic corticosteroids equivalent to prednisone 10 mg or greater in the 14 days prior to the first dose of cemiplimab
Any major surgery within 14 days prior to the first dose of cemiplimab. Patients must have recovered from any major complications before registration
Active autoimmune disease requiring systemic treatment in the past 2 years (i.e. use of disease modifying agents or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc) is not considered a form of systemic treatment
History of other prior malignancy in the last five years, with the exception of: adequately treated non-melanoma skin cancers (including multiple primary skin cancers), adequately treated in situ cancer, and other local tumors considered cured by local treatment (including melanoma)
History of allergic reactions attributed to compounds of similar chemical or biologic composition to cemiplimab or any other PD-1 or PD-L1 inhibitor
Uncontrolled, intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness / social situations that would limit compliance with study requirements
Positive pregnancy test, active pregnancy or nursing / breast-feeding, due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants
History solid organ or bone marrow transplantation
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