Cutaneous Squamous Cell CarcinomaPhase 2NCT04632433
Neoadjuvant Plus Adjuvant Treatment With Cemiplimab in Cutaneaous Squamous Cell Carcinoma
A Phase 2 study testing Cemiplimab in people with Cutaneous Squamous Cell Carcinoma, run by Fondazione Melanoma Onlus at 7 sites in Italy.
Trial summary
Neoadjuvant plus adjuvant treatment with immunotherapy may have an anti-tumor activity and reduce the risk of relapse in patients with high risk surgically resectable stage III cutaneous squamous cell carcinoma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cutaneous Squamous Cell Carcinoma
- What is being tested?
- Cemiplimab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 7 sitesItaly
- Study dates
- 10 Feb 2021to 1 Feb 2026
- 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
- Patients of either sex aged ≥18 years.
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
- Patients must have histologically or cytologically confrimed stage III cutaneous squamous cell carcinomas. The definition of resectability can be determined by the patient's surgical oncologist and verified via discussion at Multidisciplinary Tumor Conference attended by CSCC medical and surgical oncology staff. Resectable tumors are defined as having no significant vascular, neural or bony involvement.
- Patients must be medically fit enough to undergo surgery as determined by the surgical oncology team.
- Patients must have measurable disease, defined by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
Show all 9Show fewer
- Patients must have organ and marrow function
- Female subjects of childbearing potential must have a negative pregnancy test result at baseline and must practice a reliable method of contraception for the total study duration plus 16 weeks (i.e., 30 days plus the time required for cemiplimab to undergo five half lives) after the last dose of cemiplimab.
- Men who are sexually active with women of childbearing potential must practice a reliable method of contraception for the total study duration plus 16 weeks (i.e., 80 days plus the time required for cemiplimab to undergo five half-lives) after the last dose of cemiplimab.
Who cannot join
- Evidence of metastatic disease extra lymphnodal.
- Currently and previous cancer therapy (chemotherapy, radiation therapy, immunotherapy, or biologic therapy) or investigational anti-cancer drug.
- Prior malignancy within the prior 5 years, except for the following: in-situ cervical cancer, thyroid cancer (except anaplastic) or any cancer from which the patient has been disease-free for 2 years.
- Any major surgery within the last 3 weeks.
- Unwillingness or inability to follow the procedures required in the protocol.
- Uncontrolled diabetes, hypertension, pneumonitis and abnormal thyroid function or other medical conditions that may interfere with assessment of toxicity.
Show all 10Show fewer
- Subjects with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of treatment.
- Female subjects who are pregnant (positive pregnancy test), breast-feeding, or who are of childbearing potential and not practicing a reliable method of birth control.
- Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection;
- Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
Italy7 sites
Ospedale S.M. Annunziata - Azienda USL Toscana Centro
Bagno a Ripoli, Firenze, 50012
Azienda Ospedaliera Papa Giovanni XXIII
Bergamo, Bergamo, 24127
ASST Spedali Civili Brescia
Brescia
IRCCS - Istituto Scientifico Romagnolo per la Cura e lo Studio dei Tumori (I.R.S.T) S.r.l.
Meldola, Forlì-Cesena, 47014
Fondazione I.R.C.C.S. Istituto Nazionale dei Tumori
Milan, Milano, 20133
Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale"
Naples, Naples, 80131
Istituto Oncologico Veneto
Padova, Padova, 35128
About this study
Official title: A Phase II, Single Arm Study Investigating Neoadjuvant Plus Adjuvant Treatment With Cemiplimab in High Risk, Surgically Resectable, Stage III Cutaneaous Squamous Cell Carcinoma
Neoadjuvant plus adjuvant treatment with immunotherapy may have an anti-tumor activity and reduce the risk of relapse in patients with high risk surgically resectable stage III cutaneous squamous cell carcinoma.
Read the detailed description
Cutaneous squamous cell carcinoma (CSCC) is the second most common skin cancer in US. It is associated with a surgical cure rate >95% in early stage disease but a small percentage of patients develop unresectable locally advanced or metastatic CSCC. The 2018 FDA approval of Libtayo was based on a combined analysis of data from an open-label, multi-center, non-randomized Phase 2 trial known as EMPOWER-CSCC-1 (Study 1540) and two advanced CSCC expansion cohorts from a multi-center, open-label, non-randomized Phase 1 trial (Study 1423). Conventional cytotoxic chemotherapy can induce tumor responses but is often poorly tolerated, specially among older patients with CSCC. CSCC has higher mutation burden than any tumor type and immunosuppression is a known risk factor. Furthermore, PD-L1 expression has been associated with high risk disease1 suggesting that CSCC may be responsive to PD-1 checkpoint blockade.
Cemiplimab is a human anti-PD-1 monoclonal antibody, under study for patients with unresectable locally advanced and/or regionally or metastatic CSCC. It has been studied in a phase I dose escalation, where a durable radiologic complete response was achieved in CSCC patients.2-3 In this study, the partial response was 25% in locally advanced and 60% in metastatic CSCC,stable disease was 31.3% in locally advanced and 10% in metastatic CSCC, progressive disease was 25% in locally advanced and 20% in metastatic CSCC with an overall response rate of 46.2% and a disease control rate of 69.2%. The 2018 FDA approval of Libtayo was based on a combined analysis of data from an open-label, multi-center, non-randomized Phase 2 trial known as EMPOWER-CSCC-1 (Study 1540) and two advanced CSCC expansion cohorts from a multi-center, open-label, non-randomized Phase 1 trial (Study 1423). Together, the trials represent the largest prospective data set in advanced CSCC. The major efficacy outcome measures for the integrated analysis of EMPOWER-CSCC-1 and the two CSCC expansion cohorts were confirmed objective response rate (ORR), as assessed by independent central review (ICR), and ICR-assessed duration of response (DOR).
Across the entire population, the overall response rate (ORR) at a median follow-up of 8.9 months was 47% (95% CI, 38-47). The complete response (CR) rate was 4% and the partial response (PR) rate was 44%. The duration of response ranged from 1 month to over 15 months. Sixty-one percent of patients had a duration of response ≥6 months.
Among 75 patients with metastatic CSCC, the ORR was 47% (95% CI, 35-59). The CR rate was 5% and the PR rate was 41%. The duration of response ranged from 3 months to over 15 months. Sixty percent of patients had a duration of response ≥6 months. In the 33 patients with locally advanced disease, the ORR was 49% (95% CI, 31-67), comprising all PRs. The duration of response ranged from 1 month to over 13 months. Sixty-three percent of patients had a duration of response ≥6 months.
Cemiplimab therefore produced rapid, deep and durable tumor reductions in target lesions.
Cemiplimab appears to be active regardless PD-L1 expressione in the tumor and no apparent association between PD-L1 IHC results and objective responses was determined. Cemiplimab was generally well tolerated in CSCC, and most commonly associated with fatigue (23.1% prevalence), arthralgia, rash maculopapular, diarrhea, nausea, hypothyroidism (7.7%) of any grade.
The advantage of neoadjuvant trials is the availability of blood and tumor tissue samples before and after systemic therapy for the conduct of novel mechanistic and biomarker studies in the circulation and the tumor microenvironment.
Based on the available results to date, the investigators aim to conduct a phase II single arm trial to define the role of neoadjuvant plus adjuvant immunotherapy in patients with stage III CSCC. This approach has the potential to define whether neoadjuvant treatment with cemiplimab has antitumor activity and whether it reduces the risk of relapse after surgery.
- Conditions
- Cutaneous Squamous Cell Carcinoma
- Being tested
- Cemiplimab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CemiplimabDrug
350 mg every 3 weeks
| Study group | Role | What they receive |
|---|---|---|
| single arm | Experimental | Patients will receive cemiplimab at a dosage of 350 mg every 3 weeks for two cycles prior surgery. Stage III stage must be documented at screening and re-assessed prior surgery by spiral or multidetector computed tomography (CT) scan (if clinically indicated) and Positron emission tomography (PET). Postoperatively, adjuvant immunotherapy with cemiplimab will be administered at a dosage of 350 mg every 3 weeks for one year. Receives: Drug: Cemiplimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Major pathological response rate
<10% remaining viable tumour cells in resected primary tumor
Measured: 43-71 days
Secondary outcomes (4)
Recurrence-free survival
RFS - the time from start of treatment until disease recurrence (local, regional or distant) or death from any cause
Measured: At 6 and 12 months postoperative
Overall Survival
OS - the time from the date of first dose until the date of death from any cause
Measured: Until three years from last infusion
Prevalence of related AEs
Number of participants with treatment-related adverse events by grade as assessed by CTCAE v5.0
Measured: Through study treatment completion, an average of 17 months
Use of selected biomarkers to detect molecular and immunophenotypic changes
Predictive biomarkers and thier changes in tumor and blood samples will be correlated with pathological response and patient's outcome
Measured: At screening 1 and 2, at surgery, every 12 weeks during adjuvant and at recurrence of disease untill an average of 1 year from surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2020
- Study start10 Feb 2021
- Primary completion6 Feb 2023
- Study completion1 Feb 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for 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
- Model description
- Patients will receive cemiplimab at a dosage of 350 mg every 3 weeks for two cycles prior surgery. Stage III stage must be documented at screening and re-assessed prior surgery by spiral or multidetector computed tomography (CT) scan (if clinically indicated) and Positron emission tomography (PET). Postoperatively, adjuvant immunotherapy with cemiplimab will be administered at a dosage of 350 mg every 3 weeks for one year.
- Masking
- None (open label)
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fondazione Melanoma Onlus
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Paolo Ascierto, MD, Study chair, Fondazione Melanoma Onlus
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04632433
- Sponsor's protocol ID
- NEO-CESQ
- Status last verified
- Mar 2025
- First submitted
- 6 Nov 2020
- Last updated
- 13 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Single Arm Study Investigating Neoadjuvant Plus Adjuvant Treatment With Cemiplimab in High Risk, Surgically Resectable, Stage III Cutaneaous Squamous Cell Carcinoma
- ClinicalTrials.gov ID
- NCT04632433
- Acronym / sponsor ID
- NEO-CESQ
- Conditions
- Cutaneous Squamous Cell Carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- Fondazione Melanoma OnlusUniversity, hospital or other
- Study start
- 10 Feb 2021 (actual)
- Primary completion
- 6 Feb 2023 (actual)
- Study completion
- 1 Feb 2026 (estimated)
- First posted
- 17 Nov 2020 (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.
Neoadjuvant plus adjuvant treatment with immunotherapy may have an anti-tumor activity and reduce the risk of relapse in patients with high risk surgically resectable stage III cutaneous squamous cell carcinoma.
Detailed description
Cutaneous squamous cell carcinoma (CSCC) is the second most common skin cancer in US. It is associated with a surgical cure rate >95% in early stage disease but a small percentage of patients develop unresectable locally advanced or metastatic CSCC. The 2018 FDA approval of Libtayo was based on a combined analysis of data from an open-label, multi-center, non-randomized Phase 2 trial known as EMPOWER-CSCC-1 (Study 1540) and two advanced CSCC expansion cohorts from a multi-center, open-label, non-randomized Phase 1 trial (Study 1423). Conventional cytotoxic chemotherapy can induce tumor responses but is often poorly tolerated, specially among older patients with CSCC. CSCC has higher mutation burden than any tumor type and immunosuppression is a known risk factor. Furthermore, PD-L1 expression has been associated with high risk disease1 suggesting that CSCC may be responsive to PD-1 checkpoint blockade.
Cemiplimab is a human anti-PD-1 monoclonal antibody, under study for patients with unresectable locally advanced and/or regionally or metastatic CSCC. It has been studied in a phase I dose escalation, where a durable radiologic complete response was achieved in CSCC patients.2-3 In this study, the partial response was 25% in locally advanced and 60% in metastatic CSCC,stable disease was 31.3% in locally advanced and 10% in metastatic CSCC, progressive disease was 25% in locally advanced and 20% in metastatic CSCC with an overall response rate of 46.2% and a disease control rate of 69.2%. The 2018 FDA approval of Libtayo was based on a combined analysis of data from an open-label, multi-center, non-randomized Phase 2 trial known as EMPOWER-CSCC-1 (Study 1540) and two advanced CSCC expansion cohorts from a multi-center, open-label, non-randomized Phase 1 trial (Study 1423). Together, the trials represent the largest prospective data set in advanced CSCC. The major efficacy outcome measures for the integrated analysis of EMPOWER-CSCC-1 and the two CSCC expansion cohorts were confirmed objective response rate (ORR), as assessed by independent central review (ICR), and ICR-assessed duration of response (DOR).
Across the entire population, the overall response rate (ORR) at a median follow-up of 8.9 months was 47% (95% CI, 38-47). The complete response (CR) rate was 4% and the partial response (PR) rate was 44%. The duration of response ranged from 1 month to over 15 months. Sixty-one percent of patients had a duration of response ≥6 months.
Among 75 patients with metastatic CSCC, the ORR was 47% (95% CI, 35-59). The CR rate was 5% and the PR rate was 41%. The duration of response ranged from 3 months to over 15 months. Sixty percent of patients had a duration of response ≥6 months. In the 33 patients with locally advanced disease, the ORR was 49% (95% CI, 31-67), comprising all PRs. The duration of response ranged from 1 month to over 13 months. Sixty-three percent of patients had a duration of response ≥6 months.
Cemiplimab therefore produced rapid, deep and durable tumor reductions in target lesions.
Cemiplimab appears to be active regardless PD-L1 expressione in the tumor and no apparent association between PD-L1 IHC results and objective responses was determined. Cemiplimab was generally well tolerated in CSCC, and most commonly associated with fatigue (23.1% prevalence), arthralgia, rash maculopapular, diarrhea, nausea, hypothyroidism (7.7%) of any grade.
The advantage of neoadjuvant trials is the availability of blood and tumor tissue samples before and after systemic therapy for the conduct of novel mechanistic and biomarker studies in the circulation and the tumor microenvironment.
Based on the available results to date, the investigators aim to conduct a phase II single arm trial to define the role of neoadjuvant plus adjuvant immunotherapy in patients with stage III CSCC. This approach has the potential to define whether neoadjuvant treatment with cemiplimab has antitumor activity and whether it reduces the risk of relapse after surgery.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Patients will receive cemiplimab at a dosage of 350 mg every 3 weeks for two cycles prior surgery. Stage III stage must be documented at screening and re-assessed prior surgery by spiral or multidetector computed tomography (CT) scan (if clinically indicated) and Positron emission tomography (PET). Postoperatively, adjuvant immunotherapy with cemiplimab will be administered at a dosage of 350 mg every 3 weeks for one year.
| Arm | Type | Receives |
|---|---|---|
| single arm | Experimental | Drug: CemiplimabPatients will receive cemiplimab at a dosage of 350 mg every 3 weeks for two cycles prior surgery. Stage III stage must be documented at screening and re-assessed prior surgery by spiral or multidetector computed tomography (CT) scan (if clinically indicated) and Positron emission tomography (PET). Postoperatively, adjuvant immunotherapy with cemiplimab will be administered at a dosage of 350 mg every 3 weeks for one year. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Patients of either sex aged ≥18 years.
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
- Patients must have histologically or cytologically confrimed stage III cutaneous squamous cell carcinomas. The definition of resectability can be determined by the patient's surgical oncologist and verified via discussion at Multidisciplinary Tumor Conference attended by CSCC medical and surgical oncology staff. Resectable tumors are defined as having no significant vascular, neural or bony involvement.
- Patients must be medically fit enough to undergo surgery as determined by the surgical oncology team.
- Patients must have measurable disease, defined by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1.
Key exclusion criteria (10 listed)
- Evidence of metastatic disease extra lymphnodal.
- Currently and previous cancer therapy (chemotherapy, radiation therapy, immunotherapy, or biologic therapy) or investigational anti-cancer drug.
- Prior malignancy within the prior 5 years, except for the following: in-situ cervical cancer, thyroid cancer (except anaplastic) or any cancer from which the patient has been disease-free for 2 years.
- Any major surgery within the last 3 weeks.
- Unwillingness or inability to follow the procedures required in the protocol.
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 |
|---|---|---|
| Cemiplimab350 mg every 3 weeks | Drug | single arm |
Primary outcome
Major pathological response rate
Time frame: 43-71 days
<10% remaining viable tumour cells in resected primary tumor
4 secondary outcomes
Recurrence-free survival
Time frame: At 6 and 12 months postoperative
Overall Survival
Time frame: Until three years from last infusion
Prevalence of related AEs
Time frame: Through study treatment completion, an average of 17 months
Use of selected biomarkers to detect molecular and immunophenotypic changes
Time frame: At screening 1 and 2, at surgery, every 12 weeks during adjuvant and at recurrence of disease untill an average of 1 year from surgery
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 13 Mar 2025.
- Individual participant dataSharing planned: No
Related trials for Cutaneous Squamous Cell Carcinoma
RecruitingPhase 2
Treatment With Amivantamab and Hyaluronidase or Cetuximab for Advanced Skin Cancer in People With a Weakened Immune System
Locally Recurrent Skin Squamous Cell Carcinoma, Metastatic Skin Squamous Cell Carcinoma
RecruitingPhase 3
High-dose Prophylactic Gabapentin (HOPE) vs. Placebo to Prevent Opioid Use for Oral Mucositis Pain During Concurrent Chemoradiation for Head and Neck Cancer
Head and Neck Squamous Cell Carcinoma, Stage I Head and Neck Cutaneous Squamous Cell Carcinoma AJCC v8
RecruitingPhase 2
BiCaZO: A Study Combining Two Immunotherapies (Cabozantinib and Nivolumab) to Treat Patients With Advanced Melanoma or Squamous Cell Head and Neck Cancer, an immunoMATCH Pilot Study
Clinical Stage III Cutaneous Melanoma AJCC v8, Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8
RecruitingPhase 3
Testing the Addition of Anti-Cancer Drug, Cetuximab, to Standard of Care Treatment (Pembrolizumab) for Returning or Spreading Head and Neck Cancer After Previous Treatment
Metastatic Head and Neck Squamous Cell Carcinoma, Metastatic Hypopharyngeal Squamous Cell Carcinoma
Active, not recruitingPhase 2/3
Testing the Use of Investigational Drugs Atezolizumab and/or Bevacizumab With or Without Standard Chemotherapy in the Second-Line Treatment of Advanced-Stage Head and Neck Cancers
Clinical Stage IV HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, Metastatic Head and Neck Squamous Cell Carcinoma
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. This study is not recruiting at the moment.
Paolo Ascierto, MD study chair
Fondazione Melanoma Onlus
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cemiplimab in people with Cutaneous Squamous Cell Carcinoma, run by Fondazione Melanoma Onlus at 7 sites in Italy.
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 10 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: under way, not looking for participants, as of the sponsor's last update on 13 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Major pathological response rate (time frame: 43-71 days). 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 13 Mar 2025.