Recruiting
Phase 2

L19IL2 & L19TNF

Sponsor:

Philogen S.p.A.

Code:

NCT07228442

Conditions

Locally Advanced Cutaneous Squamous Cell Carcinoma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

L19IL2/L19TNF

Study Details

Brief 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). 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.

Conditions

Locally Advanced Cutaneous Squamous Cell Carcinoma

Study ID

NCT07228442

Start date

Sep, 2026

Status verified date

Jul, 2026

Completion date

Feb, 2031

Anticipated

Primary completion date

Feb, 2031

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

Study Design

Enrollment

92 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Treatment

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.

Interventions

L19IL2/L19TNF

intratumoral administrations

Primary outcome measure

  • Overall Response Rate (BORR) [ Time Frame: From enrollment up to a maximum of 160 weeks after the start of treatment ]

Central Contacts and Locations

Central contacts

Lisa Nadal

+3905771526723lisa.nadal@philogen.com

Concetta Aulicino

+39057717816regulatory@philogen.com

Locations

UC Irvine Health- Chao Family Comprehensive Cancer Center

Recruiting

Orange, California, United States, 92868-3201

Principal Investigator:

Maki MD Yamamoto

Winship Cancer Institute, Emory University

Recruiting

Atlanta, Georgia, United States, 30322

Principal Investigator:

Michael C. Lowe, MD

Dana-Farber Cancer Institute

Recruiting

Boston, Massachusetts, United States, 02215

Principal Investigator:

Emily Ruiz, MD

Duke University Medical Center

Recruiting

Durham, North Carolina, United States, 27710

Principal Investigator:

Melodi J Whitley, MD

The University of Texas MD Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030

Principal Investigator:

Michael R Migden, MD

More Information

Sponsor

Philogen S.p.A.

Last update posted

Jul 24, 2026

Last verified

Jul, 2026

Keywords

  • Cutaneous Squamous Cell Carcinoma
  • Immune Checkpoint Inhibitor
  • subcutaneous lesions
  • locally advanced
  • cutaneous lesions

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Philogen S.p.A. on 2026-07-24.