L19IL2/L19TNF in Patients With Cutaneous Squamous Cell Carcinoma

Recruiting now · Phase 2

Conditions studied: Locally Advanced Cutaneous Squamous Cell Carcinoma

In brief

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.

Key facts

Study ID

NCT07228442

Run by

Philogen S.p.A.

People needed

92

Starts

2026-09-01

Expected to finish

2031-02-01

Last updated by the study team

2026-07-24

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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.
• 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.

You may not qualify if…

• 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).
• 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.

Where it is running

• Hospital Clinic De Barcelona — Barcelona, Spain (enrolling)
• Winship Cancer Institute, Emory University — Atlanta, Georgia, United States (enrolling)
• Dana-Farber Cancer Institute — Boston, Massachusetts, United States (enrolling)
• Duke University Medical Center — Durham, North Carolina, United States (enrolling)
• Azienda Ospedaliero-Universitaria Senese — Siena, Italy (enrolling)
• UC Irvine Health- Chao Family Comprehensive Cancer Center — Orange, California, United States (enrolling)
• The University of Texas MD Anderson Cancer Center — Houston, Texas, United States (enrolling)
• Universitaetsklinikum Augsburg — Augsburg, Germany (enrolling)
• Charite Universitaetsmedizin Berlin KöR — Berlin, Germany (enrolling)
• Universitaetsklinikum Essen AöR — Essen, Germany (enrolling)
• Universitaetsklinikum Halle (Saale) AöR — Halle, Germany (enrolling)
• Universitaetsklinikum Heidelberg AöR — Heidelberg, Germany (enrolling)
• Universitaetsklinikum Schleswig-Holstein AöR — Kiel, Germany (enrolling)
• Universitaetsklinikum Tübingen AöR — Tübingen, Germany (enrolling)
• IRCCS Istituto Nazionale Tumori Fondazione Pascale — Naples, Italy (enrolling)
• Fondazione Policlinico Universitario Agostino Gemelli IRCCS — Roma, Italy (enrolling)
• Humanitas Mirasole S.p.A. — Rozzano, Italy (enrolling)
• The Ohio State University Wexner Medical Center Clinical Laboratories — Columbus, Ohio, United States
• Andreas Syngros Hospital Of Venereal And Dermatological Diseases — Athens, Greece

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.