Locally Advanced Cutaneous Squamous Cell CarcinomaPhase 2NEOPECSNCT06418724
Neoadjuvant PD-1 Inhibitor and EGFR Inhibitor in Locally Advanced Cutaneous Squamous Cell Carcinoma
A Phase 2 study testing Cetuximab and Cemiplimab in people with Locally Advanced Cutaneous Squamous Cell Carcinoma, run by Melanoma and Skin Cancer Trials Limited.
Trial summary
The NEOPECS trial is a phase II prospective, single-arm, non-randomised interventional trial for patients with borderline resectable locally advanced cutaneous squamous cell carcinoma with a 6-participant safety lead in to ensure safety of the combination in the neoadjuvant setting across 3 sites in Australia. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Locally Advanced Cutaneous Squamous Cell Carcinoma
- What is being tested?
- Cetuximab and Cemiplimab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- No sites listed yet
- Study dates
- 30 Oct 2026to 1 Dec 2030
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female > 18 years of age and able to comply with treatment, assessment and follow up
- Documentation of a locally advanced cutaneous squamous cell carcinoma diagnosis as evidenced by histopathology with available archival tissue. Locally Advanced cutaneous Squamous Cell Carcinoma (LASCC) defined as borderline resectable for surgery due to multiple recurrences, prior radiotherapy, large extension, bone erosion and/or deep infiltration beyond the subcutaneous tissue into muscle/nerve or, where curative resection may lead to unacceptable complications, morbidity or deformity, and ineligible for curative radiotherapy
- Measurable disease in accordance with iRECIST criteria OR clinically measurable disease >1cm by caliper measurement. Patients with synchronous primary cutaneous squamous cell carcinoma (cSCC) tumours will be eligible.
- Adequate bone marrow function with haemoglobin >100g/L, absolute neutrophil count > 1.5 x 109/L, platelets > 100 x 109/L). Blood transfusion is allowable.
- Adequate hepatic function with total bilirubin levels <1.5 upper limit normal range and Alanine aminotransferase (ALT) and AST levels <2.5 level normal range.
- Adequate renal function with eGFR estimated with Cockcroft Gault formula >50mL/min. Serum potassium levels 3.5 - 5.5 mmoL/L, Serum magnesium levels 0.7 - 1.05 mmol/L, Serum corrected calcium levels 2.15 - 2.55 mmol/L
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- Adequate performance status of Eastern Cooperative Oncology Group (ECOG) 0-1 as assessed by investigator
- Life expectancy of >6 months
- Able to provide written informed consent obtained from patient and ability for patient to comply with the requirements of the trial.
Who cannot join
- Distant metastatic disease (M1) including visceral or distant nodal metastases
- Prior receipt of checkpoint inhibitor therapy or anti-EGFR therapy for LASCC or any other malignancy
- Uncontrolled medical/psychiatric co-morbidity as per investigator that may jeopardize the ability of the patient to undergo trial procedures with reasonable safety
- Uncontrolled autoimmune disease requiring active immune-suppression within 1 year of enrolment
- Corticosteroid use of >10mg daily of oral prednisone within 2 weeks of Cycle 1 Day 1 (C1D1)
- Known history of interstitial lung disease, non-infectious pneumonitis or uncontrolled diseases including pulmonary fibrosis, acute lung diseases.
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- Uncontrolled infection with human immunodeficiency virus, hepatitis B, or hepatitis C infection; or has a diagnosis of immunodeficiency
- Transplant recipient
- Hepatitis C virus (HCV) and hepatitis B virus (HBV) testing will be performed at screening
- Controlled HIV infection (undetectable viral load (HIV RNA PCR) and Cluster of differentiation 4 (CD4) counts above 350 either spontaneously or on a stable antiviral regimen) is permitted. Monitoring will be performed per local standards.
- Controlled hepatitis B antibody positive infection (HBsAg+) is permitted providing a serum hepatitis B virus DNA PCR that is below the limit of detection and patient is receiving anti-viral therapy for hepatitis B. Periodic monitoring of HBV DNA is required. Anti-viral therapy for at least 6 months post the last dose of investigational study drug is required.
- Controlled hepatitis C virus antibody positive (HCV Ab+) is permitted (undetectable HCV RNA by PCR either spontaneously or in response to a successful prior course of anti-HCV therapy).
- History of another malignancy within 5 years prior to trial registration. A past history of adequately treated carcinoma-in-situ, basal cell carcinoma of skin, or superficial transitional cell carcinoma of the bladder is permitted. Patients with a history of other malignancies are eligible if they have been continuously disease free for at least 3 years after definitive primary treatment and low expected risk of recurrence.
- Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with trial protocol and follow-up schedule, including alcohol and drug abuse.
- Pregnancy, lactation or inadequate contraception. Women must be post-menopausal, infertile or willing to use reliable means of contraception. Women of childbearing potential must have a negative pregnancy test done within 7 days prior to registration. Men must have been surgically sterilized or willing to use double barrier contraception.
- Sexually active men and women of childbearing potential who are unwilling to practice highly effective contraception prior to the start of the first treatment, during the study, and for at least 6 months after the last dose of investigational drug.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
The NEOPECS trial is a phase II prospective, single-arm, non-randomised interventional trial for patients with borderline resectable locally advanced cutaneous squamous cell carcinoma with a 6-participant safety lead in to ensure safety of the combination in the neoadjuvant setting across 3 sites in Australia.
Read the detailed description
As cutaneous squamous cell carcinoma typically occurs on sun-exposed areas of the head and neck, surgical resection of advanced disease can have significant morbidity and disfigurement and strategies to downstage disease prior to surgery, improve chance of R0 resection and reduce the risk of post-surgical relapse remain an area of need.
This study aims to determine the preliminary activity and tolerability of neo-adjuvant combination cemiplimab and cetuximab in unresectable locally advanced cutaneous squamous cell carcinoma by clinical downstaging rate to resectable status.
- Being tested
- Cetuximab, Cemiplimab
- Keywords
- immunotherapy, neoadjuvant therapy, PD-1 inhibitor, EGFR inhibitor, cetuximab, cemiplimab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CetuximabDrug
Also called Erbitux
Cetuximab is a monoclonal antibody against epidermal growth factor receptor (EGFR). EGFR is over-expressed in many human cancers, including colorectal cancers.
CemiplimabDrug
Also called Libtayo
Cemiplimab is a fully human immunoglobulin G4 (IgG4) monoclonal antibody that binds to the programmed cell death-1 (PD-1) receptor and blocks its interaction with its ligands programmed death-ligand 1 (PD-L1) and programmed death-ligand 2 (PD-L2). Engagement of PD-1 with its ligands PD-L1 and PD-L2, which are expressed by antigen presenting cells and may be expressed by tumour cells and/or other cells in the tumour microenvironment, results in inhibition of T cell function such as proliferation, cytokine secretion, and cytotoxic activity. Cemiplimab potentiates T cell responses, including antitumour responses, through blockade of PD-1 binding to PD-L1 and PD-L2 ligands.
| Study group | Role | What they receive |
|---|---|---|
| Cetuximab and Cemiplimab | Experimental | All patients will be administered the same treatment combination.
Cemiplimab will be administered 350mg intravenously every 21 days. A maximum of 4 cycles will be given.
Cetuximab will be administered 400mg/m2 loading dose on day 1 and 250mg/m2 on day 8 and day 15 for a 21 day cycle for first cycle. Cetuximab will be administered 250mg/m2 on day 1, 8 and 15 for a 21 day cycle for subsequent cycles for 4 cycles. Receives: Drug: Cetuximab; Drug: Cemiplimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Preliminary activity
The primary preliminary activity endpoint will be the achievement of clinical downstaging from borderline resectable status to either resectable status or surgery avoidance due to complete metabolic response with no residual pathological disease as deemed by Multi-Disciplinary Team (MDT) consensus evaluation following up to 4 cycles of neoadjuvant therapy.
Measured: 3 months
Secondary outcomes (8)
Treatment safety and feasibility as assessed by NCI CTCAE v5
Safety and feasibility by assessment of Common Terminology Criteria for Adverse Events (CTCAE) V5.0 with the incidence of ≥ Grade 3 adverse events, < Grade 3 adverse events and SAEs and AEs leading to study treatment discontinuation.
Measured: 12 months
Treatment safety and feasibility as assessed by rate of R0 resection
Safety and feasibility by assessment of change in rate of R0 resection. R0 resection is defined no residual tumour in surgically removed specimen of curative intent per local and central pathology review.
Measured: 12 months
Pathological response rate
Preliminary efficacy by assessment of pathological response rate, including complete (0% residual tumour cells) and major (0-10% residual tumour cells) pathological responses, by blinded central pathology review. Complete pathological response (pCR) defined as absence of viable tumor cells in surgical specimen. Major pathological response (MPR) defined as 0-10% viable tumor cells in surgical specimen.
Measured: 12 months
Overall response rate (ORR)
Preliminary efficacy by assessment of overall response rate (ORR) as per Modifed Response Evaluation Criteria in Solid Tumors for immune based therapeutics (iRECIST) criteria or investigator caliper assessment where disease is un-measurable by CT or MRI modalities
Measured: 12 months
Progression free survival (PFS)
Preliminary efficacy by assessment of 12-month and median PFS using the Kaplan-Meier method. PFS is defined as the interval from date of registration to the date of first evidence of disease progression or death, whichever occurs first.
Measured: 12 months
Event-free survival (EFS)
Preliminary efficacy by assessment of 12-month and median EFS using the Kaplan-Meier method. EFS is defined as the interval from date of registration to progressive disease or adverse events precluding surgery, inability to undergo complete (R0) resection, disease recurrence or death from any cause.
Measured: 12 months
Overall survival (OS)
Preliminary efficacy by assessment of 12-month and median OS using the Kaplan-Meier method. OS is defined as the interval from date of registration to date of death from any cause, or the date of last known follow-up alive.
Measured: 12 months
Change in predicted difficulty of surgical resection and repair
Change in predicted difficulty of surgical resection and repair pre- and post-neoadjuvant therapy as measured with paired surgeon-rated scaling "scale for predicted operability of cutaneous SCC". Scale scores range from Inoperable disease (A) to Complete response (F)
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 May 2024
- Study start30 Oct 2026 (estimated)
- Primary completion30 Jul 2030 (estimated)
- Study completion1 Dec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Locally Advanced Cutaneous Squamous Cell CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 27 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Melanoma and Skin Cancer Trials Limited
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jia (Jenny) Liu, MD, PhD, FRACP, Study chair, Kinghorn Cancer Centre/St Vincent's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06418724
- Sponsor's protocol ID
- 02.23
- Acronym
- NEOPECS
- Status last verified
- Mar 2026
- First submitted
- 12 Apr 2024
- Last updated
- 7 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neoadjuvant PD-1 Inhibitor and EGFR Inhibitor in Locally Advanced Cutaneous Squamous Cell Carcinoma
- ClinicalTrials.gov ID
- NCT06418724
- Acronym / sponsor ID
- NEOPECS / 02.23
- Keywords
- immunotherapy, neoadjuvant therapy, PD-1 inhibitor, EGFR inhibitor, cetuximab, cemiplimab
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 27 participants (estimated)
- Lead sponsor
- Melanoma and Skin Cancer Trials LimitedUniversity, hospital or other
- Study start
- 30 Oct 2026 (estimated)
- Primary completion
- 30 Jul 2030 (estimated)
- Study completion
- 1 Dec 2030 (estimated)
- First posted
- 17 May 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The NEOPECS trial is a phase II prospective, single-arm, non-randomised interventional trial for patients with borderline resectable locally advanced cutaneous squamous cell carcinoma with a 6-participant safety lead in to ensure safety of the combination in the neoadjuvant setting across 3 sites in Australia.
Detailed description
As cutaneous squamous cell carcinoma typically occurs on sun-exposed areas of the head and neck, surgical resection of advanced disease can have significant morbidity and disfigurement and strategies to downstage disease prior to surgery, improve chance of R0 resection and reduce the risk of post-surgical relapse remain an area of need.
This study aims to determine the preliminary activity and tolerability of neo-adjuvant combination cemiplimab and cetuximab in unresectable locally advanced cutaneous squamous cell carcinoma by clinical downstaging rate to resectable status.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Cetuximab and Cemiplimab | Experimental | Drug: Cetuximab, Drug: CemiplimabAll patients will be administered the same treatment combination. Cemiplimab will be administered 350mg intravenously every 21 days. A maximum of 4 cycles will be given. Cetuximab will be administered 400mg/m2 loading dose on day 1 and 250mg/m2 on day 8 and day 15 for a 21 day cycle for first cycle. Cetuximab will be administered 250mg/m2 on day 1, 8 and 15 for a 21 day cycle for subsequent cycles for 4 cycles. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Male or female > 18 years of age and able to comply with treatment, assessment and follow up
- Documentation of a locally advanced cutaneous squamous cell carcinoma diagnosis as evidenced by histopathology with available archival tissue. Locally Advanced cutaneous Squamous Cell Carcinoma (LASCC) defined as borderline resectable for surgery due to multiple recurrences, prior radiotherapy, large extension, bone erosion and/or deep infiltration beyond the subcutaneous tissue into muscle/nerve or, where curative resection may lead to unacceptable complications, morbidity or deformity, and ineligible for curative radiotherapy
- Measurable disease in accordance with iRECIST criteria OR clinically measurable disease >1cm by caliper measurement. Patients with synchronous primary cutaneous squamous cell carcinoma (cSCC) tumours will be eligible.
- Adequate bone marrow function with haemoglobin >100g/L, absolute neutrophil count > 1.5 x 109/L, platelets > 100 x 109/L). Blood transfusion is allowable.
- Adequate hepatic function with total bilirubin levels <1.5 upper limit normal range and Alanine aminotransferase (ALT) and AST levels <2.5 level normal range.
Key exclusion criteria (16 listed)
- Distant metastatic disease (M1) including visceral or distant nodal metastases
- Prior receipt of checkpoint inhibitor therapy or anti-EGFR therapy for LASCC or any other malignancy
- Uncontrolled medical/psychiatric co-morbidity as per investigator that may jeopardize the ability of the patient to undergo trial procedures with reasonable safety
- Uncontrolled autoimmune disease requiring active immune-suppression within 1 year of enrolment
- Corticosteroid use of >10mg daily of oral prednisone within 2 weeks of Cycle 1 Day 1 (C1D1)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CetuximabAlso: ErbituxCetuximab is a monoclonal antibody against epidermal growth factor receptor (EGFR). EGFR is over-expressed in many human cancers, including colorectal cancers. | Drug | Cetuximab and Cemiplimab |
| CemiplimabAlso: LibtayoCemiplimab is a fully human immunoglobulin G4 (IgG4) monoclonal antibody that binds to the programmed cell death-1 (PD-1) receptor and blocks its interaction with its ligands programmed death-ligand 1 (PD-L1) and programmed death-ligand 2 (PD-L2). Engagement of PD-1 with its ligands PD-L1 and PD-L2, which are expressed by antigen presenting cells and may be expressed by tumour cells and/or other cells in the tumour microenvironment, results in inhibition of T cell function such as proliferation, cytokine secretion, and cytotoxic activity. Cemiplimab potentiates T cell responses, including antitumour responses, through blockade of PD-1 binding to PD-L1 and PD-L2 ligands. | Drug | Cetuximab and Cemiplimab |
Primary outcome
Preliminary activity
Time frame: 3 months
The primary preliminary activity endpoint will be the achievement of clinical downstaging from borderline resectable status to either resectable status or surgery avoidance due to complete metabolic response with no residual pathological disease as deemed by Multi-Disciplinary Team (MDT) consensus evaluation following up to 4 cycles of neoadjuvant therapy.
8 secondary outcomes
Treatment safety and feasibility as assessed by NCI CTCAE v5
Time frame: 12 months
Treatment safety and feasibility as assessed by rate of R0 resection
Time frame: 12 months
Pathological response rate
Time frame: 12 months
Overall response rate (ORR)
Time frame: 12 months
Progression free survival (PFS)
Time frame: 12 months
Event-free survival (EFS)
Time frame: 12 months
Overall survival (OS)
Time frame: 12 months
Change in predicted difficulty of surgical resection and repair
Time frame: 3 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Oct 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Jia (Jenny) Liu, MD, PhD, FRACP study chair
Kinghorn Cancer Centre/St Vincent's Hospital
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cetuximab and Cemiplimab in people with Locally Advanced Cutaneous Squamous Cell Carcinoma, run by Melanoma and Skin Cancer Trials Limited.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 7 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Melanoma and Skin Cancer Trials Ltd Project Officer (+61 3 9903 9022, neopecs@masc.org.au), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Preliminary activity (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Oct 2026.