L19IL2/L19TNF in Patients With Cutaneous Squamous Cell Carcinoma

NCT07228442 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: PH-L19IL2TNFSCC-06/242025-523231-19-00
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 2

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

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (BORR)

  Best Overall Response Rate (BORR) as defined by the RECIST 1.1. criteria according to an Independent Central Review (ICR).

  From enrollment up to a maximum of 160 weeks after the start of treatment

Study Arms (1)

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.

Drug: L19IL2/L19TNF

Interventions

L19IL2/L19TNF DRUG

intratumoral administrations

Treatment

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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, age 18 - 100 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).
• 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.
• 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 (estrogenand 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.
• Presence of active severe bacterial or viral infections or other severe concurrent 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.
• 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.
• Known history of allergy to IL2, TNF, or other human proteins/peptides/antibodies.

Sponsors & Collaborators

• Philogen S.p.A.: lead

Study Sites (2)

Winship Cancer Institute, Emory University

Atlanta, Georgia, 30322, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Interventions

daromun

Central Study Contacts

Lisa Nadal

CONTACT

+3905771526723; lisa.nadal@philogen.com

Concetta Aulicino

CONTACT

+39057717816; regulatory@philogen.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 7, 2025
• First Posted: November 14, 2025
• Study Start: February 1, 2026
• Primary Completion (Estimated): February 1, 2031
• Study Completion (Estimated): February 1, 2031
• Last Updated: March 9, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)