Conditions

• Locally Recurrent Skin Squamous Cell Carcinoma
• Metastatic Skin Squamous Cell Carcinoma

Eligibility

Eligible Ages

Over 18 Years

Eligible Sex

All

Accepts Healthy Volunteers

No

Criteria

Inclusion Criteria:

- Participants must have pathologically proven diagnosis of cutaneous squamous cell
carcinoma based on pathology from original diagnosis or from a metastatic/recurrent
lesion

- Participants must have measurable or non-measurable disease per RECIST 1.1 and must
have their disease assessed by CT of chest/abdomen/pelvis (with contrast unless
contraindicated) within 28 days prior to registration for measurable disease or
within 42 days prior to registration for non-measurable disease. All known sites of
disease must be assessed and documented on the Baseline Tumor Assessment Form
(RECIST 1.1). Any lesions assessed using a non-diagnostic positron emission
tomography (PET)/CT of chest/abdomen/pelvis will be considered non-measurable
lesions. Pleural effusions, ascites and laboratory parameters are not acceptable as
the only evidence of disease. Participants whose only measurable disease is within a
previous radiation therapy port must demonstrate clearly progressive disease (in the
opinion of the treating investigator) prior to registration to be considered
measurable

- NOTE: All diseases must be assessed and documented on the baseline tumor
assessment form

- Participants with exclusively locally recurrent disease must have either a
contraindication to surgical treatment of lesions (i.e., complete resection is not
possible or not expected to be clinically beneficial or resection conferring
significant cosmetic or functional concerns) or have refused surgical or radiation
treatment

- Participants must be immunocompromised, defined as below. For cases where there is a
lack of clarity, it is highly recommended study teams reach out to Drs. Swiecicki
and Geiger for discussion:

- An active diagnosis of either chronic lymphocytic leukemia (CLL) or acute
leukemia, regardless of whether actively receiving therapy OR

- A diagnosis of lymphoma or multiple myeloma either on antineoplastic therapy,
or within 6 months after therapy completion OR

- Recipient of an organ transplant (excluding corneal transplants or lung
transplants)

- If a transplant patient, documentation from the patient's transplant
physician confirming that the patient's allograft is stable. Documentation
must be dated within 180 days of registration OR

- Autoimmune disease under active treatment with an immunosuppressive medication
(as defined below)

- Autoimmune diseases include but are not limited to: systemic lupus
erythematosus, rheumatoid arthritis, inflammatory bowel disease,
vasculitis, myasthenia gravis, Guillain-Barre syndrome, autoimmune
hepatitis, scleroderma, primary biliary cirrhosis, pemphigus, and bullous
pemphigoid

- Vitiligo, psoriasis, type 1 diabetes mellitus, hypothyroidism, or
resolved childhood asthma/atopy are not eligible diagnoses

- Immunosuppressant medications include the following:

- Tumor necrosis factor (TNF) inhibitors (adalimumab, certolizumab,
etanercept, golimumab, and infliximab)

- Interleukin inhibitors (anakinra, ustekinumab, secukinumab,
sarilumab, siltuximab, sulfasalazine, tildrakizumab, tocilizumab,
chloroquine, and hydroxychloroquine)

- Janus kinase (JAK) inhibitors (baricitinib, filgotinib, and
tofacitinib)

- Calcineurin inhibitors (cyclosporine and tacrolimus)

- Metabolic inhibitors (azathioprine, leflunomide, mercaptopurine,
methotrexate)

- mTOR (mammalian target of rapamycin) inhibitors (sirolimus
[rapamycin], everolimus, and zotarolimus)

- Inosine monophosphate dehydrogenase inhibitors (mycophenolate)

- Phosphodiesterase inhibitors (apremilast)

- B cell inhibitors (rituximab)

- T cell inhibitors (abatacept)

- Glucocorticoids

- Active treatment is defined as current use of any one or more of the
following:

- Oral glucocorticoid therapy (Prednisone equivalent > 10 mg/day) for
30 days prior to registration

- Oral or subcutaneous immunosuppressive therapy for 90 days or more
prior to registration

- Two or more doses of intravenous non corticosteroid immunosuppressant
within 90 days prior to registration

- Participants with treated brain metastases must show no evidence of progression on
follow-up brain imaging after central nervous system (CNS)-directed therapy

- Participants with new or progressive brain metastases (active brain metastases) or
leptomeningeal disease must not require immediate CNS specific treatment at the time
of study registration or anticipated during the first cycle of therapy

- Participants must not have had prior treatment with cetuximab or another EGFR
inhibitor within the last 365 days

- Participant must be ≥ 18 years old at the time of registration

- Participant must have Zubrod Performance Status of 0-2

- Participant must have a complete medical history and physical exam within 28 days
prior to registration

- Leukocytes ≥ 3 x 10^3/uL (within 14 days prior to registration)

- Absolute neutrophil count ≥ 1.5 x 10^3/uL (within 14 days prior to registration)

- Platelets ≥ 100 x 10^3/uL (within 14 days prior to registration)

- Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) unless history of
Gilbert's disease. Participants with history of Gilbert's disease must have total
bilirubin ≤ 5 x institutional ULN (within 14 days prior to registration)

- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 3 × institutional
ULN with the exception of subjects with documented liver metastases: AST and/or ALT
≤ 5.0 x institutional ULN (within 14 days prior to registration)

- Participants must have a measured OR calculated creatinine clearance ≥ 30 mL/min
using the following Cockcroft-Gault Formula. This specimen must have been drawn and
processed within 14 days prior to registration

- Participants must not have an active or past medical history of interstitial lung
disease (ILD)/pneumonitis, including drug-induced or radiation ILD/pneumonitis

- Participants must not have a history of lung transplantation

- Participants must not have a history of pulmonary graft versus host disease (GVHD)

- Participants must have adequate cardiac function. Participants with known history or
current symptoms of cardiac disease, must have a clinical risk assessment of cardiac
function using the New York Heart Association Functional Classification. To be
eligible for this trial, participants must be class 2B or better

- Participants with a history human immunodeficiency virus (HIV)-infection must be on
effective anti-retroviral therapy at registration and have undetectable viral load
test on the most recent test results obtained within 6 months prior to registration

- Participants with a history of chronic hepatitis B virus (HBV) infection must have
undetectable HBV viral load while on suppressive therapy on the most recent test
results obtained within 6 months prior to registration, if indicated

- Participants with a history of hepatitis C virus (HCV) infection must have been
treated and cured. Participants currently being treated for HCV infection must have
undetectable HCV viral load test on the most recent test results obtained within 6
months prior to registration, if indicated

- Participants must not have an uncontrolled illness, including but not limited to:

- Ongoing or active infection (includes infection requiring treatment with
antimicrobial therapy [participants will be required to complete antibiotics 1
week prior to starting study treatment])

- Active bleeding diathesis

- Any ophthalmologic condition that is clinically unstable

- Participants must not have a prior or concurrent malignancy whose natural history or
treatment (in the opinion of the treating physician) has the potential to interfere
with the safety or efficacy assessment of the investigational regimen

- Participants must not be pregnant or nursing (nursing includes breast milk fed to an
infant by any means, including from the breast, milk expressed by hand, or pumped)
due to known toxicities of amivantamab. Individuals who are of reproductive
potential must have agreed to use an effective contraceptive method with details
provided as a part of the consent process. A person who has had menses at any time
in the preceding 12 consecutive months or who has semen likely to contain sperm is
considered to be of "reproductive potential." In addition to routine contraceptive
methods, "effective contraception" also includes refraining from sexual activity
that might result in pregnancy and surgery intended to prevent pregnancy (or with a
side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy,
bilateral tubal ligation/occlusion, and vasectomy with testing showing no sperm in
the semen. Participants must agree not to donate ova or sperm for the purpose of
reproduction during the study and for a minimum of 6 months after receiving the last
dose of study treatment. For female participants of childbearing potential, a
negative pregnancy test is required within 72 hours prior to registration

- Participants must be offered the opportunity to participate in specimen banking

Recruiting Locations

Study Contact

Detailed Description

PRIMARY OBJECTIVES: I. To evaluate the safety and preliminary efficacy of amivantamab monotherapy in patients with locoregionally incurable or metastatic cutaneous squamous cell carcinoma and an active immunosuppressed condition. (Cohort A) II. To compare progression-free survival (PFS) of amivantamab monotherapy versus cetuximab monotherapy in patients with locoregionally incurable or metastatic cutaneous squamous cell carcinoma and an active immunosuppressed condition. (Cohort B) SECONDARY OBJECTIVES: I. To estimate the frequency and severity of toxicities in each cohort and treatment arm. II. To estimate confirmed objective response rate (ORR) (ORR, confirmed complete and partial responses by Response Evaluation Criteria in Solid Tumors [RECIST] version [v] 1.1) in each cohort and treatment arm. III. To estimate duration of objective response, time to progression, time to next treatment, and overall survival in each cohort and treatment arm. IV. To estimate ORR and progression free survival (PFS) in each cohort and treatment arm in subgroups defined by reason for immunosuppression: transplant, autoimmune disease, hematologic malignancy, or other reason. BANKING OBJECTIVE: I. To bank specimens for future correlative studies. OUTLINE: Patients in cohort A are assigned to arm I, patients in cohort B are randomized to arm I or II. ARM I: Patients receive amivantamab and hyaluronidase subcutaneously (SC) over at least 5 minutes on days 1, 8, 15 and 22 of cycle 1 and day 1 of subsequent cycles. Cycles repeat every 28 days for 24 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection on study and computed tomography (CT) and/or magnetic resonance imaging (MRI) throughout the study. ARM II: Patients receive cetuximab intravenously (IV) over 60-120 minutes on days 1 and 15 of each cycle. Cycles repeat every 28 days for 24 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection on study and CT and/or MRI throughout the study. After completion of study treatment, patients are followed up, per the treating investigator, for up 3 years.