Treatment With Amivantamab and Hyaluronidase or Cetuximab for Advanced Skin Cancer in People With a Weakened Immune System
A Randomized Phase II Study of Amivantamab (JNJ-61186372) and Hyaluronidase (rHuPH20) Versus Cetuximab in Immunocompromised Participants With Recurrent Inoperable or Metastatic Cutaneous Squamous Cell Carcinoma
3 other identifiers
interventional
86
1 country
30
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Mar 2026
Typical duration for phase_2
30 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 27, 2025
CompletedFirst Posted
Study publicly available on registry
June 29, 2025
CompletedStudy Start
First participant enrolled
March 23, 2026
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 28, 2029
ExpectedStudy Completion
Last participant's last visit for all outcomes
February 28, 2029
May 1, 2026
April 1, 2026
2.9 years
June 27, 2025
April 30, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
Incidence of toxicity of interest (cohort A)
Defined as grade 3 or 4 skin rash that does not recover within 14 days, grade 3 or 4 non-hematologic toxicity that does not recover within 7 days, grade 4 hematologic toxicity including febrile neutropenia or organ transplant failure (for transplant patients only).
Up to completion of the first cycle (cycle length = 28 days)
Progression free survival (PFS) (cohort B)
From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause, up to 3 years
Secondary Outcomes (6)
Organ rejection
Up to 5 years
Overall survival (OS)
From date of registration to date of death due to any cause, up to 5 years
PFS
From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause, up to 5 years
Time to next treatment
Up to 3 years
Time to progression
Up to 3 years
- +1 more secondary outcomes
Study Arms (2)
Arm I (amivantamab and hyaluronidase)
EXPERIMENTALPatients 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.
Arm II (cetuximab)
ACTIVE COMPARATORPatients receive cetuximab 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.
Interventions
Undergo MRI
Given IV
Undergo CT scan
Given SC
Undergo blood sample collection
Eligibility Criteria
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 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)
- +39 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (30)
Banner MD Anderson Cancer Center
Gilbert, Arizona, 85234, United States
UC San Diego Moores Cancer Center
La Jolla, California, 92093, United States
Yale University
New Haven, Connecticut, 06520, United States
Smilow Cancer Hospital Care Center-Trumbull
Trumbull, Connecticut, 06611, United States
Smilow Cancer Hospital Care Center - Waterford
Waterford, Connecticut, 06385, United States
Carle at The Riverfront
Danville, Illinois, 61832, United States
Carle Physician Group-Effingham
Effingham, Illinois, 62401, United States
Carle Physician Group-Mattoon/Charleston
Mattoon, Illinois, 61938, United States
Carle BroMenn Medical Center
Normal, Illinois, 61761, United States
Carle Cancer Institute Normal
Normal, Illinois, 61761, United States
Carle Cancer Center
Urbana, Illinois, 61801, United States
University of Michigan Rogel Cancer Center
Ann Arbor, Michigan, 48109, United States
Memorial Sloan Kettering Basking Ridge
Basking Ridge, New Jersey, 07920, United States
Memorial Sloan Kettering Monmouth
Middletown, New Jersey, 07748, United States
Memorial Sloan Kettering Bergen
Montvale, New Jersey, 07645, United States
Memorial Sloan Kettering Commack
Commack, New York, 11725, United States
Memorial Sloan Kettering Westchester
Harrison, New York, 10604, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
Memorial Sloan Kettering Nassau
Uniondale, New York, 11553, United States
UH Seidman Cancer Center at UH Avon Health Center
Avon, Ohio, 44011, United States
UHHS-Chagrin Highlands Medical Center
Beachwood, Ohio, 44122, United States
University of Cincinnati Cancer Center-UC Medical Center
Cincinnati, Ohio, 45219, United States
Case Western Reserve University
Cleveland, Ohio, 44106, United States
University of Cincinnati Cancer Center-West Chester
West Chester, Ohio, 45069, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, 15232, United States
Froedtert Menomonee Falls Hospital
Menomonee Falls, Wisconsin, 53051, United States
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226, United States
Froedtert and MCW Moorland Reserve Health Center
New Berlin, Wisconsin, 53151, United States
Drexel Town Square Health Center
Oak Creek, Wisconsin, 53154, United States
Froedtert West Bend Hospital/Kraemer Cancer Center
West Bend, Wisconsin, 53095, United States
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Paul L Swiecicki
SWOG Cancer Research Network
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 27, 2025
First Posted
June 29, 2025
Study Start
March 23, 2026
Primary Completion (Estimated)
February 28, 2029
Study Completion (Estimated)
February 28, 2029
Last Updated
May 1, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will share
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.