Recruiting

Phase 2

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

Sponsor:

National Cancer Institute (NCI)

Code:

NCT07042295

Conditions

Locally Recurrent Skin Squamous Cell Carcinoma

Metastatic Skin Squamous Cell Carcinoma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Amivantamab and Recombinant Human Hyaluronidase

Biospecimen Collection

Cetuximab

Computed Tomography

Magnetic Resonance Imaging

Study Details

Brief summary:

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.

Conditions

Locally Recurrent Skin Squamous Cell Carcinoma

Metastatic Skin Squamous Cell Carcinoma

Study ID

NCT07042295

Start date

Mar 23, 2026

Status verified date

Sep, 2026

Completion date

Feb 28, 2029

Anticipated

Primary completion date

Feb 28, 2029

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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 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:

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
Participants must have Zubrod Performance Status of 0-2
Participants 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

Study Design

Enrollment

86 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Arm I (amivantamab and hyaluronidase)

Patients receive amivantamab and hyaluronidase 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 CT scan and/or MRI throughout the study.

active comparator: Arm II (cetuximab)

Patients receive cetuximab IV 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.

Interventions

Amivantamab and Recombinant Human Hyaluronidase

Given SC

Biospecimen Collection

Undergo blood sample collection

Cetuximab

Given IV

Computed Tomography

Undergo CT scan

Magnetic Resonance Imaging

Undergo MRI

Primary outcome measure

Incidence of toxicity of interest (cohort A) [ Time Frame: Up to completion of the first cycle (cycle length = 28 days) ]
Progression free survival (PFS) (cohort B) [ Time Frame: From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause, up to 3 years ]

Central Contacts and Locations

Locations

University of Alabama at Birmingham Cancer Center

Recruiting

Birmingham, Alabama, United States, 35233

Contacts

Site Public Contact

gingerreeves@uabmc.edu

Principal Investigator:

Mehran Yusuf

Banner MD Anderson Cancer Center

Recruiting

Gilbert, Arizona, United States, 85234

Contacts

Site Public Contact

602-747-9738

Principal Investigator:

Saba H. Radhi

UC San Diego Moores Cancer Center

Recruiting

La Jolla, California, United States, 92093

Contacts

Site Public Contact

858-822-5354 cancercto@ucsd.edu

Principal Investigator:

Soo Park

USC / Norris Comprehensive Cancer Center

Recruiting

Los Angeles, California, United States, 90033

Contacts

Site Public Contact

323-865-0451

Principal Investigator:

Gino K. In

UCHealth University of Colorado Hospital

Recruiting

Aurora, Colorado, United States, 80045

Contacts

Site Public Contact

720-848-0650

Principal Investigator:

Sapna P. Patel

Yale University

Recruiting

New Haven, Connecticut, United States, 06520

Contacts

Site Public Contact

203-785-5702 canceranswers@yale.edu

Principal Investigator:

Barbara A. Burtness

Smilow Cancer Hospital Care Center-Trumbull

Recruiting

Trumbull, Connecticut, United States, 06611

Contacts

Site Public Contact

203-785-5702 canceranswers@yale.edu

Principal Investigator:

Barbara A. Burtness

Smilow Cancer Hospital Care Center - Waterford

Recruiting

Waterford, Connecticut, United States, 06385

Contacts

Site Public Contact

203-785-5702 canceranswers@yale.edu

Principal Investigator:

Barbara A. Burtness

UM Sylvester Comprehensive Cancer Center at Coral Gables

Recruiting

Coral Gables, Florida, United States, 33146

Contacts

Site Public Contact

305-243-2647

Principal Investigator:

Leonel F. Hernandez-Aya

UM Sylvester Comprehensive Cancer Center at Coral Springs

Recruiting

Coral Springs, Florida, United States, 33065

Contacts

Site Public Contact

305-243-2647

Principal Investigator:

Leonel F. Hernandez-Aya

UM Sylvester Comprehensive Cancer Center at Deerfield Beach

Recruiting

Deerfield Beach, Florida, United States, 33442

Contacts

Site Public Contact

305-243-2647

Principal Investigator:

Leonel F. Hernandez-Aya

UM Sylvester Comprehensive Cancer Center at Doral

Recruiting

Doral, Florida, United States, 33166

Contacts

Site Public Contact

kginnity@med.miami.edu

Principal Investigator:

Leonel F. Hernandez-Aya

University of Miami Miller School of Medicine-Sylvester Cancer Center

Recruiting

Miami, Florida, United States, 33136

Contacts

Site Public Contact

305-243-2647

Principal Investigator:

Leonel F. Hernandez-Aya

UM Sylvester Comprehensive Cancer Center at Kendall

Recruiting

Miami, Florida, United States, 33176

Contacts

Site Public Contact

305-243-2647

Principal Investigator:

Leonel F. Hernandez-Aya

University of Miami Sylvester Comprehensive Cancer Center at Sole Mia

Recruiting

North Miami, Florida, United States, 33181

Contacts

Site Public Contact

kginnity@med.miami.edu

Principal Investigator:

Leonel F. Hernandez-Aya

UM Sylvester Comprehensive Cancer Center at Plantation

Recruiting

Plantation, Florida, United States, 33324

Contacts

Site Public Contact

305-243-2647

Principal Investigator:

Leonel F. Hernandez-Aya

Emory University Hospital Midtown

Recruiting

Atlanta, Georgia, United States, 30308

Contacts

Site Public Contact

888-946-7447

Principal Investigator:

Jose A. Monteiro de Oliveira Novaes

Emory University Hospital/Winship Cancer Institute

Recruiting

Atlanta, Georgia, United States, 30322

Contacts

Site Public Contact

404-778-1868

Principal Investigator:

Jose A. Monteiro de Oliveira Novaes

University of Chicago Comprehensive Cancer Center

Recruiting

Chicago, Illinois, United States, 60637

Contacts

Site Public Contact

773-702-8222 cancerclinicaltrials@bsd.uchicago.edu

Principal Investigator:

Noura Choudhury

Carle at The Riverfront

Recruiting

Danville, Illinois, United States, 61832

Contacts

Site Public Contact

800-446-5532 Research@Carle.com

Principal Investigator:

Suparna Mantha

Carle Physician Group-Effingham

Recruiting

Effingham, Illinois, United States, 62401

Contacts

Site Public Contact

800-446-5532 Research@carle.com

Principal Investigator:

Suparna Mantha

Ingalls Memorial Hospital

Recruiting

Harvey, Illinois, United States, 60426

Contacts

Site Public Contact

708-915-4673 clinicaltrials@ingalls.org

Principal Investigator:

Kimberly R. Kruczek

Carle Physician Group-Mattoon/Charleston

Recruiting

Mattoon, Illinois, United States, 61938

Contacts

Site Public Contact

800-446-5532 Research@carle.com

Principal Investigator:

Suparna Mantha

UC Comprehensive Cancer Center at Silver Cross

Recruiting

New Lenox, Illinois, United States, 60451

Contacts

Site Public Contact

773-702-8222 cancerclinicaltrials@bsd.uchicago.edu

Principal Investigator:

Noura Choudhury

Carle BroMenn Medical Center

Recruiting

Normal, Illinois, United States, 61761

Contacts

Site Public Contact

800-446-5532 Research@Carle.com

Principal Investigator:

Suparna Mantha

Carle Cancer Institute Normal

Recruiting

Normal, Illinois, United States, 61761

Contacts

Site Public Contact

800-446-5532 Research@Carle.com

Principal Investigator:

Suparna Mantha

University of Chicago Medicine-Orland Park

Recruiting

Orland Park, Illinois, United States, 60462

Contacts

Site Public Contact

773-702-8222 cancerclinicaltrials@bsd.uchicago.edu

Principal Investigator:

Noura Choudhury

Carle Cancer Center

Recruiting

Urbana, Illinois, United States, 61801

Contacts

Site Public Contact

800-446-5532 Research@carle.com

Principal Investigator:

Suparna Mantha

UChicago Medicine Northwest Indiana

Recruiting

Crown Point, Indiana, United States, 46307

Contacts

Site Public Contact

855-702-8222 cancerclinicaltrials@bsd.uchicago.edu

Principal Investigator:

Noura Choudhury

University of Michigan Rogel Cancer Center

Recruiting

Ann Arbor, Michigan, United States, 48109

Contacts

Site Public Contact

800-865-1125 CancerAnswerLine@med.umich.edu

Principal Investigator:

Paul L. Swiecicki

Henry Ford Hospital

Recruiting

Detroit, Michigan, United States, 48202

Contacts

Site Public Contact

313-916-3721 CTOResearch@hfhs.org

Principal Investigator:

Amy M. Weise

Memorial Sloan Kettering Basking Ridge

Recruiting

Basking Ridge, New Jersey, United States, 07920

Contacts

Site Public Contact

212-639-7592

Principal Investigator:

Lara A. Dunn

Memorial Sloan Kettering Monmouth

Recruiting

Middletown, New Jersey, United States, 07748

Contacts

Site Public Contact

212-639-7592

Principal Investigator:

Lara A. Dunn

Memorial Sloan Kettering Bergen

Recruiting

Montvale, New Jersey, United States, 07645

Contacts

Site Public Contact

212-639-7592

Principal Investigator:

Lara A. Dunn

Memorial Sloan Kettering Commack

Recruiting

Commack, New York, United States, 11725

Contacts

Site Public Contact

212-639-7592

Principal Investigator:

Lara A. Dunn

Memorial Sloan Kettering Westchester

Recruiting

Harrison, New York, United States, 10604

Contacts

Site Public Contact

212-639-7592

Principal Investigator:

Lara A. Dunn

Memorial Sloan Kettering Cancer Center

Recruiting

New York, New York, United States, 10065

Contacts

Site Public Contact

212-639-7592

Principal Investigator:

Lara A. Dunn

Memorial Sloan Kettering Nassau

Recruiting

Uniondale, New York, United States, 11553

Contacts

Site Public Contact

212-639-7592

Principal Investigator:

Lara A. Dunn

Duke University Medical Center

Recruiting

Durham, North Carolina, United States, 27710

Contacts

Site Public Contact

888-275-3853

Principal Investigator:

Eric Powers

UH Seidman Cancer Center at UH Avon Health Center

Recruiting

Avon, Ohio, United States, 44011

Contacts

Site Public Contact

800-641-2422

Principal Investigator:

Ankit Mangla

UHHS-Chagrin Highlands Medical Center

Recruiting

Beachwood, Ohio, United States, 44122

Contacts

Site Public Contact

800-641-2422 CTUReferral@UHhospitals.org

Principal Investigator:

Ankit Mangla

University of Cincinnati Cancer Center-UC Medical Center

Recruiting

Cincinnati, Ohio, United States, 45219

Contacts

Site Public Contact

513-584-7698 cancer@uchealth.com

Principal Investigator:

Rekha T. Chaudhary

Case Western Reserve University

Recruiting

Cleveland, Ohio, United States, 44106

Contacts

Site Public Contact

800-641-2422 CTUReferral@UHhospitals.org

Principal Investigator:

Ankit Mangla

University of Cincinnati Cancer Center-West Chester

Recruiting

West Chester, Ohio, United States, 45069

Contacts

Site Public Contact

513-584-7698 cancer@uchealth.com

Principal Investigator:

Rekha T. Chaudhary

University of Oklahoma Health Sciences Center

Recruiting

Oklahoma City, Oklahoma, United States, 73104

Contacts

Site Public Contact

405-271-8777 ou-clinical-trials@ouhsc.edu

Principal Investigator:

Minh Phan

Penn State Milton S Hershey Medical Center

Recruiting

Hershey, Pennsylvania, United States, 17033-0850

Contacts

Site Public Contact

717-531-3779 CTO@hmc.psu.edu

Principal Investigator:

Joseph J. Drabick

UPMC Hillman Cancer Center

Recruiting

Pittsburgh, Pennsylvania, United States, 15232

Contacts

Site Public Contact

412-647-8073

Principal Investigator:

Diwakar Davar

UT MD Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030

Contacts

Site Public Contact

866-632-6789 askmdanderson@mdanderson.org

Principal Investigator:

Michael Wotman

Huntsman Cancer Institute/University of Utah

Recruiting

Salt Lake City, Utah, United States, 84112

Contacts

Site Public Contact

888-424-2100 cancerinfo@hci.utah.edu

Principal Investigator:

Siwen Hu-Lieskovan

Froedtert Menomonee Falls Hospital

Recruiting

Menomonee Falls, Wisconsin, United States, 53051

Contacts

Site Public Contact

262-257-5100

Principal Investigator:

Stuart J. Wong

Medical College of Wisconsin

Recruiting

Milwaukee, Wisconsin, United States, 53226

Contacts

Site Public Contact

414-805-3666

Principal Investigator:

Stuart J. Wong

Froedtert and MCW Moorland Reserve Health Center

Recruiting

New Berlin, Wisconsin, United States, 53151

Contacts

Site Public Contact

414-805-0505

Principal Investigator:

Stuart J. Wong

Drexel Town Square Health Center

Recruiting

Oak Creek, Wisconsin, United States, 53154

Contacts

Site Public Contact

414-805-0505

Principal Investigator:

Stuart J. Wong

Froedtert West Bend Hospital/Kraemer Cancer Center

Recruiting

West Bend, Wisconsin, United States, 53095

Contacts

Site Public Contact

414-805-0505

Principal Investigator:

Stuart J. Wong

More Information

Sponsor

National Cancer Institute (NCI)

Last update posted

Sep 30, 2026

Last verified

Sep, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-01. This information was provided to ClinicalTrials.gov by National Cancer Institute (NCI) on 2026-09-30. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.