Recruiting
Phase 2

L19IL2, L19TNF, L19IL2/L19TNF

Sponsor:

Philogen S.p.A.

Code:

NCT07227350

Conditions

Locally Advanced Basal Cell Carcinoma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

L19IL2

L19TNF

L19IL2/L19TNF

Study Details

Brief summary:

Open label, randomized study in patients with LaBCC not eligible or refusing surgery or radiation therapy according to the evaluation of a local interdisciplinary tumor board. The primary objective of the study is to evaluate the efficacy of L19IL2 or L19TNF or L19IL2/L19TNF, the secondary objectives of this study are to evaluate efficacy, safety and pharmacokinetics of immunocytokines. A minimum of 60 patients and a maximum of 180 evaluable patients will be randomized in a 1:1:1 ratio to one of the three different treatment arms of the study and will receive intralesional injections of: (i) Monotherapy 13 Mio IU (\~2.17 mg) L19IL2; or (ii) Monotherapy 0.4 mg L19TNF; or (iii) Combination of 13 Mio IU L19IL2 + 0.4 mg L19TNF, once weekly for 4 consecutive weeks. Patients will be followed for a maximum of 156 weeks after beginning of treatment.

Conditions

Locally Advanced Basal Cell Carcinoma

Study ID

NCT07227350

Start date

Jun 1, 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 with high risk, locally advanced histologically confirmed (non-metastatic, node negative, single or multifocal), BCC and amenable to intratumoral injection, not eligible or refusing surgery or radiation therapy according to the evaluation of a local interdisciplinary tumor board.
  • Patients with at least one injectable and measurable cutaneous or subcutaneous lesion.
  • Patients must not have received prior HHIs and checkpoint inhibitors systemic treatment.
  • Patients may have received prior surgery and/or radiation therapy.
  • Radiotherapy must have been previously administered for their locally advanced BCC, unless radiotherapy is contraindicated or inappropriate (e.g., hypersensitivity to radiation due to genetic syndrome such as Gorlin syndrome, limitations because of location of tumor, or cumulative prior radiotherapy dose). For patients whose locally advanced BCC has been irradiated, disease must have progressed after radiation.
  • Patients must have a histologically confirmed disease that is considered to be inoperable or medical contraindication to surgery or radiotherapy, in the opinion of a Mohs dermatologic surgeon, head and neck surgeon, plastic surgeon or surgical/medical oncologist. Acceptable medical contraindications to surgery include:

  • BCC that has recurred in the same location after two or more surgical procedures and curative resection is deemed unlikely;
  • Anticipated substantial morbidity and/or deformity from surgery (e.g., removal of all or part of a facial structure, such as nose, ear, eyelid, eye; or requirement for limb amputation);
  • Medical conditions predisposing to poor surgical outcome (e.g., diabetes with history of poor wound healing);
  • Other conditions considered to be medically contraindicating must be discussed with the Medical Monitor before enrolling the patient.
  • Prior radiotherapy to the target lesions must be completed at least 4 weeks prior to first study drug administration, with all acute RT-related toxicities resolved to ≤ Grade 1.
  • Male or female patients, who are capable of giving consent, age ≥ 18 years.
  • ECOG Performance Status/WHO Performance Status ≤ 1.
  • 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, vasectomized 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 squamous-cell carcinoma of the skin (surgically removed 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.
  • Current topical or systemic chemotherapy, targeted therapy immunotherapy.
  • Patients with node positive BCC who are candidates for checkpoint inhibitor therapy.
  • 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.
  • 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.
  • 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

180 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: L19IL2

Patient will receive intralesional injections of monotherapy 13 Mio IU (\~2.17 mg) L19IL2. Frequency and duration are identical for all arms.

experimental: L19IL2/L19TNF

Patient will receive intralesional injections of Combination of 13 Mio IU L19IL2 + 0.4 mg L19TNF. Frequency and duration are identical for all arms.

experimental: L19TNF

Patient will receive intralesional injections of monotherapy 0.4 mg L19TNF. Frequency and duration are identical for all arms.

Interventions

L19IL2

Intratumoral injections

L19TNF

Intratumoral injections

L19IL2/L19TNF

Intratumoral injections

Primary outcome measure

  • Best Overall Response Rate [ Time Frame: from enrollment to week 16 ]

Central Contacts and Locations

Central contacts

Lisa Nadal

05771526723lisa.nadal@philogen.com

Concetta Aulicino

+39057717816regulatory@philogen.com

Locations

H. Lee Moffitt Cancer Center and Research Institute Hospital, Inc.

Recruiting

Tampa, Florida, United States, 33612

Principal Investigator:

Jonathan S Zager, MD

Winship Cancer Institute, Emory University

Recruiting

Atlanta, Georgia, United States, 30322

Principal Investigator:

Michael C. Lowe, 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 31, 2026

Last verified

Jul, 2026

Keywords

  • Basal Cell Carcinoma
  • locally advanced
  • subcutaneous lesions
  • 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 2026-07-31.