Locally Advanced Cutaneous Squamous Cell CarcinomaPhase 2NCT07228442
L19IL2/L19TNF in Patients With Cutaneous Squamous Cell Carcinoma
A Phase 2 study testing L19IL2/L19TNF in people with Locally Advanced Cutaneous Squamous Cell Carcinoma, run by Philogen S.p.A. at 19 sites in 5 countries.
Trial summary
Open-label, single-arm, multicenter study in patients with locally advanced, histologically confirmed Cutaneous Squamous Cell Carcinoma (LacSCC) amenable to intratumoral injection, who have progressed on or are intolerant to Immune Checkpoint Inhibitor (ICI). 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?
- L19IL2/L19TNF
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 92 participants
- Where
- 19 sitesin 5 countries
- Study dates
- Sep 2026to Feb 2031
- 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 must have histologically documented, locally advanced cSCC.
- Patients must have at least one injectable and measurable cutaneous or subcutaneous lesion.
- Patients must have locally advanced cSCC that has progressed on or cannot tolerate ICI treatment (adjuvant or first line) as assessed by a local multidisciplinary tumor board.
- Patients with nodal, regional or in transit injectable cSCC lesions.
- Patients must be willing to provide tissue from a core or excisional biopsy of a tumor lesion at screening and for confirmation of Objective Response or Stable Disease.
- Male or female patients, who are capable of giving consent, age ≥ 18 years.
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- ECOG Performance Status/WHO Performance Status ≤ 2.
- Hemoglobin > 10.0 g/dL.
- Platelets > 100 x 109/L.
- ALT and AST, GGT and Lipase ≤ 1.5 x the upper limit of normal (ULN).
- All acute toxic effects (excluding alopecia) of any prior therapy must have resolved to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE v. 5.0) Grade ≤ 1 unless otherwise specified.
- Women of childbearing potential (WOCBP) must have negative pregnancy test results at screening. WOCBP must be using, from screening to three months following the last study drug administration, highly effective contraception methods, as defined by the "Recommendations for contraception and pregnancy testing in clinical trials" issued by the Head of Medicine Agencies' Clinical Trial Facilitation Group and which include, for instance, progesterone-only or combined (estrogen- and progesterone-containing) hormonal contraception associated with inhibition of ovulation, intrauterine devices, intrauterine hormone-releasing systems, bilateral tubal occlusion, vasectomised partner.
- Male patients with WOCBP partners must agree to use simultaneously two acceptable methods of contraception (i.e. spermicidal gel plus condom) from the screening to three months following the last study drug administration.
- Willingness and ability to comply with the scheduled visits, treatment plan, laboratory tests and other study procedures.
Who cannot join
- Presence of concomitant malignancies, with the exception of any cancer curatively treated more than 3 years prior to study entry and of tumors with a negligible risk for metastasis or death, such as adequately treated basal cell carcinoma of the skin (surgically removed at least 4 weeks prior to study entry), ductal carcinoma in situ of the breast, or carcinoma in situ of the cervix, early-stage asymptomatic CLL and not under active treatment (Rai 0, Binet A) will be eligible for the study.
- Radiation therapy on the tumor sites in the 4 weeks prior to study drug administration.
- Current topical or systemic chemotherapy, immunotherapy.
- Presence of visceral metastasis.
- disease/infection requiring therapy, including positive tests for human immunodeficiency virus (HIV)-1 or HIV-2 serum antibody, hepatitis B virus (HBV), or hepatitis C virus (HCV). For HBV serology, the determination of HBsAg and anti-HBcAg Ab is required. In patients with serology documenting previous exposure to HBV, negative serum HBV-DNA is required. For HCV, HCV-RNA or HCV antibody test is required. Subjects with a positive test for HCV antibody but no detection of HCV-RNA indicating no current infection are eligible.
- History within the last year of acute or subacute coronary syndromes including myocardial infarction, unstable or severe stable angina pectoris, inadequately treated cardiac arrhythmias and heart insufficiency (any grade, New York Heart Association (NYHA) criteria).
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- Any abnormalities observed during baseline ECG investigations that are considered clinically significant by the investigator.
- Known arterial aneurysms.
- Chronically impaired renal function as indicated by creatinine clearance < 60 mL/min/1.73m2 or for patients older than 65 years without albuminuria or proteinuria, creatinine clearance < 45 mL/min/1.73m2.
- INR > 3.
- Uncontrolled hypertension.
- Known uncontrolled coagulopathy or bleeding disorder.
- Known hepatic cirrhosis or severe pre-existing hepatic impairment.
- Moderate to severe respiratory failure.
- Active autoimmune disease that has required systemic treatment in past 2 years.
- Patients have a diagnosis of immunodeficiency or are receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug. Limited use of corticosteroids to treat or prevent acute hypersensitivity reactions and asthma/COPD is not considered an exclusion criterion.
- Known history of allergy to IL2, TNF, or other human proteins/peptides/antibodies.
- Pregnancy or breast-feeding.
- Ischemic peripheral vascular disease (Grade IIb-IV).
- Severe diabetic retinopathy.
- Recovery from major trauma including surgery within 4 weeks prior to enrollment.
- Solid organ transplant recipient or patient with iatrogenic or pathologic severe immune suppression.
- Patients with a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
- Patients who have received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin, and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.
- Any conditions that in the opinion of the investigator could hamper compliance with the study protocol.
Trial locations and contacts
19 sites in 5 countries. Contact the study team or a site near you to ask about taking part.
19 sites in 5 countries
Germany7 sites, 7 recruiting
- Recruiting
Universitaetsklinikum Augsburg
Augsburg, 86179
Julia Welzel
- Recruiting
Charite Universitaetsmedizin Berlin KöR
Berlin, 10117
Thomas Eigentler, Prof.
- Recruiting
Universitaetsklinikum Essen AöR
Essen, 45147
Dirk Schadendorf, Prof.
- Recruiting
Universitaetsklinikum Halle (Saale) AöR
Halle, 06120
Johannes Wohlrab, Prof.
- Recruiting
Universitaetsklinikum Heidelberg AöR
Heidelberg, 69120
Jessica Hassel, Prof.
- Recruiting
Universitaetsklinikum Schleswig-Holstein AöR
Kiel, 24105
Katharina Kahler, Prof.
- Recruiting
Universitaetsklinikum Tübingen AöR
Tübingen, 72076
Lukas Flatz, Prof.
United States6 sites, 6 recruiting
- Recruiting
Winship Cancer Institute, Emory University
Atlanta, Georgia, 30322
Michael C. Lowe, MD
- Recruiting
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Emily Ruiz, MD
- Not yet recruiting
The Ohio State University Wexner Medical Center Clinical Laboratories
Columbus, Ohio, 43210
Carlo Contreras, MD
- Recruiting
Duke University Medical Center
Durham, North Carolina, 27710
Melodi J Whitley, MD
- Recruiting
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Michael R Migden, MD
- Recruiting
UC Irvine Health- Chao Family Comprehensive Cancer Center
Orange, California, 92868-3201
Maki MD Yamamoto
Italy4 sites, 4 recruiting
- Recruiting
IRCCS Istituto Nazionale Tumori Fondazione Pascale
Naples, 80131
Paolo Ascierto, Prof.
- Recruiting
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Roma, 00168
Ketty Peris, Prof.
- Recruiting
Humanitas Mirasole S.p.A.
Rozzano, 20089
Paolo Bossi, Prof.
- Recruiting
Azienda Ospedaliero-Universitaria Senese
Siena, 53100
Annamaria Di Giacomo, Prof.
Greece1 site, 1 recruiting
- Not yet recruiting
Andreas Syngros Hospital Of Venereal And Dermatological Diseases
Athens, 16121
Alexandros Stratigos, Prof.
Spain1 site, 1 recruiting
- Recruiting
Hospital Clinic De Barcelona
Barcelona, 08036
Augustin Toll Abello
About this study
Official title: A Phase 2 Study of Intratumoral Administration of L19IL2/L19TNF in Locally Advanced Cutaneous Squamous Cell Carcinoma Patients Progressing on or Intolerant to Systemic Treatment
Open-label, single-arm, multicenter study in patients with locally advanced, histologically confirmed Cutaneous Squamous Cell Carcinoma (LacSCC) amenable to intratumoral injection, who have progressed on or are intolerant to Immune Checkpoint Inhibitor (ICI). The primary objective of the study is to evaluate the activity of intratumoral L19IL2/L19TNF, while the secondary objective is to assess the safety and efficacy. The patients will receive multiple intratumoral administrations of combined L19IL2 and L19TNF to all injectable cutaneous and subcutaneous lesions once weekly for up to 4 weeks: for those who have a partial response or stable disease as their best response, a second 4-week course L19IL2/L19TNF of four weekly injections may be administered as per treating physician judgement. Patients will be followed for a maximum of 160 weeks after beginning of treatment.
Read the detailed description
Tumor Assessment (TA) visits will be performed at Week 8 (Day 50 from the beginning of treatment), Week 12 (Day 78), and then every 8 weeks for the first year of Follow-up (FU). During second and third years of FU, TA visits will be performed every 12 Weeks. In case a response (CR, PR) or stable disease is observed, a confirmatory assessment of the tumor response will be performed 4 weeks after the TA visit, when the response was first recorded.
Confirmation of response will be assessed by histopathological analysis of specimens from the skin treated area by multiple punch biopsies. Confirmation of tumor responses will be centrally reviewed by an independent committee (Independent Central Review, ICR).
Patients will be followed for overall survival (OS) after a relapse or progression, and any further treatment given will be recorded until LPLV. Phone contact or any other documented contact with the patient will be recorded every 6 months for OS assessment from treatment start until the death of the patient, withdrawal of consent or until study completion (LPLV).
L19IL2/L19TNF will be administered to eligible patients under the supervision of the investigator or identified sub-investigator(s). Patients will receive intratumoral administrations of L19IL2/L19TNF into injectable cutaneous, subcutaneous tumors and nodal or in transit metastasis once weekly for up to 4 weeks. On the day of each treatment visit, all tumors to be injected should be measured and recorded (using caliper/ruler for cutaneous lesions and/or ultrasound for subcutaneous lesions). The recommended volume to be injected into the tumor(s) is dependent on the size of the lesion(s). The maximum dose to be administered in a single treatment visit is: 13 MioIU L19IL2 + 0.4 mg L19TNF. It is recommended that each lesion should receive the maximum amount possible to inject due to tumor properties at each visit.
- Being tested
- L19IL2/L19TNF
- Keywords
- Cutaneous Squamous Cell Carcinoma, Immune Checkpoint Inhibitor, subcutaneous lesions, locally advanced, cutaneous lesions
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
L19IL2/L19TNFDrug
intratumoral administrations
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | the patients will receive multiple intratumoral administrations of a mixture of L19IL2 and L19TNF to all injectable cutaneous and subcutaneous lesions once weekly for up to 4 weeks. Receives: Drug: L19IL2/L19TNF |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate (BORR)
Best Overall Response Rate (BORR) as defined by the RECIST 1.1. criteria according to an Independent Central Review (ICR).
Measured: From enrollment up to a maximum of 160 weeks after the start of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Nov 2025
- Study startSep 2026 (estimated)
- Primary completionFeb 2031 (estimated)
- Study completionFeb 2031 (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.
- More trials run by Philogen S.p.A.The sponsor's other registered studies.
- 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
- 92 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Philogen S.p.A.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07228442
- Sponsor's protocol ID
- PH-L19IL2TNFSCC-06/24
- Other IDs
- 2025-523231-19-00, 2025
- Status last verified
- Jul 2026
- First submitted
- 7 Nov 2025
- Last updated
- 24 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Study of Intratumoral Administration of L19IL2/L19TNF in Locally Advanced Cutaneous Squamous Cell Carcinoma Patients Progressing on or Intolerant to Systemic Treatment
- ClinicalTrials.gov ID
- NCT07228442
- Acronym / sponsor ID
- PH-L19IL2TNFSCC-06/24
- Keywords
- Cutaneous Squamous Cell Carcinoma, Immune Checkpoint Inhibitor, subcutaneous lesions, locally advanced, cutaneous lesions
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 92 participants (estimated)
- Lead sponsor
- Philogen S.p.A.Industry (pharma, biotech, devices)
- Study start
- Sep 2026 (estimated)
- Primary completion
- Feb 2031 (estimated)
- Study completion
- Feb 2031 (estimated)
- First posted
- 14 Nov 2025 (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.
Open-label, single-arm, multicenter study in patients with locally advanced, histologically confirmed Cutaneous Squamous Cell Carcinoma (LacSCC) amenable to intratumoral injection, who have progressed on or are intolerant to Immune Checkpoint Inhibitor (ICI). The primary objective of the study is to evaluate the activity of intratumoral L19IL2/L19TNF, while the secondary objective is to assess the safety and efficacy. The patients will receive multiple intratumoral administrations of combined L19IL2 and L19TNF to all injectable cutaneous and subcutaneous lesions once weekly for up to 4 weeks: for those who have a partial response or stable disease as their best response, a second 4-week course L19IL2/L19TNF of four weekly injections may be administered as per treating physician judgement. Patients will be followed for a maximum of 160 weeks after beginning of treatment.
Detailed description
Tumor Assessment (TA) visits will be performed at Week 8 (Day 50 from the beginning of treatment), Week 12 (Day 78), and then every 8 weeks for the first year of Follow-up (FU). During second and third years of FU, TA visits will be performed every 12 Weeks. In case a response (CR, PR) or stable disease is observed, a confirmatory assessment of the tumor response will be performed 4 weeks after the TA visit, when the response was first recorded.
Confirmation of response will be assessed by histopathological analysis of specimens from the skin treated area by multiple punch biopsies. Confirmation of tumor responses will be centrally reviewed by an independent committee (Independent Central Review, ICR).
Patients will be followed for overall survival (OS) after a relapse or progression, and any further treatment given will be recorded until LPLV. Phone contact or any other documented contact with the patient will be recorded every 6 months for OS assessment from treatment start until the death of the patient, withdrawal of consent or until study completion (LPLV).
L19IL2/L19TNF will be administered to eligible patients under the supervision of the investigator or identified sub-investigator(s). Patients will receive intratumoral administrations of L19IL2/L19TNF into injectable cutaneous, subcutaneous tumors and nodal or in transit metastasis once weekly for up to 4 weeks. On the day of each treatment visit, all tumors to be injected should be measured and recorded (using caliper/ruler for cutaneous lesions and/or ultrasound for subcutaneous lesions). The recommended volume to be injected into the tumor(s) is dependent on the size of the lesion(s). The maximum dose to be administered in a single treatment visit is: 13 MioIU L19IL2 + 0.4 mg L19TNF. It is recommended that each lesion should receive the maximum amount possible to inject due to tumor properties at each visit.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Drug: L19IL2/L19TNFthe patients will receive multiple intratumoral administrations of a mixture of L19IL2 and L19TNF to all injectable cutaneous and subcutaneous lesions once weekly for up to 4 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Patients must have histologically documented, locally advanced cSCC.
- Patients must have at least one injectable and measurable cutaneous or subcutaneous lesion.
- Patients must have locally advanced cSCC that has progressed on or cannot tolerate ICI treatment (adjuvant or first line) as assessed by a local multidisciplinary tumor board.
- Patients with nodal, regional or in transit injectable cSCC lesions.
- Patients must be willing to provide tissue from a core or excisional biopsy of a tumor lesion at screening and for confirmation of Objective Response or Stable Disease.
Key exclusion criteria (25 listed)
- Presence of concomitant malignancies, with the exception of any cancer curatively treated more than 3 years prior to study entry and of tumors with a negligible risk for metastasis or death, such as adequately treated basal cell carcinoma of the skin (surgically removed at least 4 weeks prior to study entry), ductal carcinoma in situ of the breast, or carcinoma in situ of the cervix, early-stage asymptomatic CLL and not under active treatment (Rai 0, Binet A) will be eligible for the study.
- Radiation therapy on the tumor sites in the 4 weeks prior to study drug administration.
- Current topical or systemic chemotherapy, immunotherapy.
- Presence of visceral metastasis.
- disease/infection requiring therapy, including positive tests for human immunodeficiency virus (HIV)-1 or HIV-2 serum antibody, hepatitis B virus (HBV), or hepatitis C virus (HCV). For HBV serology, the determination of HBsAg and anti-HBcAg Ab is required. In patients with serology documenting previous exposure to HBV, negative serum HBV-DNA is required. For HCV, HCV-RNA or HCV antibody test is required. Subjects with a positive test for HCV antibody but no detection of HCV-RNA indicating no current infection are eligible.
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 |
|---|---|---|
| L19IL2/L19TNFintratumoral administrations | Drug | Treatment |
Primary outcome
Overall Response Rate (BORR)
Time frame: From enrollment up to a maximum of 160 weeks after the start of treatment
Best Overall Response Rate (BORR) as defined by the RECIST 1.1. criteria according to an Independent Central Review (ICR).
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 24 Jul 2026.
- Individual participant dataSharing planned: No
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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.
19 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing L19IL2/L19TNF in people with Locally Advanced Cutaneous Squamous Cell Carcinoma, run by Philogen S.p.A. at 19 sites in 5 countries.
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 14 inclusion and 25 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: looking for participants now, as of the sponsor's last update on 24 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 19 sites in Germany, United States, Italy, Greece, Spain. 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?
Contact Lisa Nadal (+3905771526723, lisa.nadal@philogen.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Response Rate (BORR) (time frame: From enrollment up to a maximum of 160 weeks after the start of treatment). 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 24 Jul 2026.