Treatment With Amivantamab and Hyaluronidase or Cetuximab for Advanced Skin Cancer in People With a Weakened Immune System

Recruiting now · Phase 2

Conditions studied: Locally Recurrent Skin Squamous Cell Carcinoma, Metastatic Skin Squamous Cell Carcinoma

In brief

This phase II trial compares the effect of amivantamab and hyaluronidase to cetuximab for the treatment of skin (cutaneous) squamous cell carcinoma that has come back after a period of improvement and has not spread to other parts of the body (locally recurrent) or that has spread from where it first started (primary site) to other places in the body (metastatic). Amivantamab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Hyaluronidase is an endoglycosidase. It helps to keep amivantamab in the body longer, so that the medications will have a greater effect. Cetuximab is in a class of medications called monoclonal antibodies. It binds to a protein called EGFR, which is found on some types of cancer cells. This may help keep cancer cells from growing. Giving amivantamab and hyaluronidase may be as effective as cetuximab for the treatment of locally recurrent or metastatic cutaneous squamous cell carcinoma.

Key facts

Study ID

NCT07042295

Run by

National Cancer Institute (NCI)

People needed

86

Starts

2026-03-23

Expected to finish

2029-02-28

Last updated by the study team

2026-08-05

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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 or MRI 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 diagnosis of either chronic lymphocytic leukemia (CLL), acute leukemia, myelodysplastic syndrome, polycythemia vera, or myelofibrosis 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:

Where it is running

• University of Alabama at Birmingham Cancer Center — Birmingham, Alabama, United States (enrolling)
• Banner MD Anderson Cancer Center — Gilbert, Arizona, United States (enrolling)
• UC San Diego Moores Cancer Center — La Jolla, California, United States (enrolling)
• USC / Norris Comprehensive Cancer Center — Los Angeles, California, United States (enrolling)
• UCHealth University of Colorado Hospital — Aurora, Colorado, United States (enrolling)
• Yale University — New Haven, Connecticut, United States (enrolling)
• Smilow Cancer Hospital Care Center-Trumbull — Trumbull, Connecticut, United States (enrolling)
• Smilow Cancer Hospital Care Center - Waterford — Waterford, Connecticut, United States (enrolling)
• University of Chicago Comprehensive Cancer Center — Chicago, Illinois, United States (enrolling)
• Carle at The Riverfront — Danville, Illinois, United States (enrolling)
• Carle Physician Group-Effingham — Effingham, Illinois, United States (enrolling)
• Carle Physician Group-Mattoon/Charleston — Mattoon, Illinois, United States (enrolling)
• UC Comprehensive Cancer Center at Silver Cross — New Lenox, Illinois, United States (enrolling)
• Carle BroMenn Medical Center — Normal, Illinois, United States (enrolling)
• Carle Cancer Institute Normal — Normal, Illinois, United States (enrolling)
• University of Chicago Medicine-Orland Park — Orland Park, Illinois, United States (enrolling)
• Carle Cancer Center — Urbana, Illinois, United States (enrolling)
• UChicago Medicine Northwest Indiana — Crown Point, Indiana, United States (enrolling)
• University of Michigan Rogel Cancer Center — Ann Arbor, Michigan, United States (enrolling)
• Henry Ford Hospital — Detroit, Michigan, United States (enrolling)
• Memorial Sloan Kettering Basking Ridge — Basking Ridge, New Jersey, United States (enrolling)
• Memorial Sloan Kettering Monmouth — Middletown, New Jersey, United States (enrolling)
• Memorial Sloan Kettering Bergen — Montvale, New Jersey, United States (enrolling)
• Memorial Sloan Kettering Commack — Commack, New York, United States (enrolling)
• Memorial Sloan Kettering Westchester — Harrison, New York, United States (enrolling)

Full record on ClinicalTrials.gov

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