Clinical Trials /

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

NCT04315701

Description:

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.

Related Conditions:
  • Skin Squamous Cell Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A PD-1 Checkpoint Inhibitor (Cemiplimab) for High-Risk Localized, Locally Recurrent, or Regionally Advanced Skin Cancer
  • Official Title: Evaluating the PD-1 Checkpoint Inhibitor, Cemiplimab, as Neoadjuvant Therapy in High Risk Localized, Locally Recurrent, and Regionally Advanced Cutaneous Squamous Cell Carcinoma: A Phase II Pilot Study

Clinical Trial IDs

  • ORG STUDY ID: 14SK-19-1
  • SECONDARY ID: NCI-2020-01247
  • SECONDARY ID: 14SK-19-1
  • SECONDARY ID: P30CA014089
  • NCT ID: NCT04315701

Conditions

  • Recurrent Skin Squamous Cell Carcinoma
  • Resectable Skin Squamous Cell Carcinoma
  • Stage I Skin Cancer
  • Stage II Skin Cancer
  • Stage III Skin Cancer

Interventions

DrugSynonymsArms
CemiplimabCemiplimab RWLC, Cemiplimab-rwlc, Libtayo, REGN2810Treatment (cemiplimab, surgical resection)

Purpose

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.

Detailed Description

      PRIMARY OBJECTIVE:

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

      SECONDARY OBJECTIVES:

      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.

      EXPLORATORY OBJECTIVES:

      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.

      OUTLINE:

      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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (cemiplimab, surgical resection)ExperimentalPatients receive cemiplimab 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.
  • Cemiplimab

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Confirmed pathologic partial response
Time Frame:Up to 24 months after completion of study treatment
Safety Issue:
Description:Defined by presence of < 50% malignant cells. Descriptive statistics will be used to summarize the measurements.

Secondary Outcome Measures

Measure:Pathologic complete response rate
Time Frame:Up to 24 months after completion of study treatment
Safety Issue:
Description:Descriptive statistics will be used to summarize the measurements.
Measure:Objective response rate
Time Frame:At 9 weeks
Safety Issue:
Description:Measured by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1. Descriptive statistics will be used to summarize the measurements.
Measure:Progression-free survival
Time Frame:From start of treatment to time of progression or death whichever comes first, assessed at 12 months
Safety Issue:
Description:Measured by RECIST v1.1. Descriptive statistics will be used to summarize the measurements.
Measure:Incidence of toxicities
Time Frame:Up to 24 months after completion of study treatment
Safety Issue:
Description:All toxicities will be summarized and graded according to maximum grade by Common Terminology Criteria for Adverse Events v4. Descriptive statistics will be used to summarize the measurements.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of Southern California

Last Updated

March 17, 2020