Intratumoral Administration of Daromun in Non-melanoma Skin Cancer Patients

Inclusion Criteria:

• High-risk, localized (non-metastatic, node negative, single or multifocal) BCC or cSCCamenable to intratumoral injection.
• Patients with injectable and measurable regional cutaneous or subcutaneous in-transitor satellite metastasis but without regional nodal involvement are also eligible.
• Male or female patients, age 18 - 100 years.
• ECOG Performance Status/WHO Performance Status ≤ 1.
• Hemoglobin > 10.0 g/dL.
• Platelets > 100 x 10^9/L.
• ALT and AST, GGT and Lipase ≤ 1.5 x the upper limit of normal (ULN).
• Serum creatinine < 1.5 x ULN and GFR > 60 mL/min.
• All acute toxic effects (excluding alopecia) of any prior therapy must have resolvedto 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 atscreening. WOCBP must be using, from screening to three months following the laststudy drug administration, highly effective contraception methods, as defined by the "Recommendations for contraception and pregnancy testing in clinical trials" issued bythe 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, vasectomisedpartner.
• Male patients with WOCBP partners must agree to use simultaneously two acceptablemethods of contraception (i.e. spermicidal gel plus condom) from the screening tothree 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:

• Previous or concurrent cancer type that is distinct from the cancers being evaluatedin this study, except any cancer curatively treated more than 2 years prior to studyentry.
• Patients may have previously received topical or systemic chemotherapy, immunotherapyor radiation therapy on the tumor sites. Such therapies must be completed at least 4weeks prior to study drug administration.
• Patients with node positive BCC/cSCC who are candidate to SHH inhibitor or checkpointinhibitor therapy.
• Presence of active severe bacterial or viral infections or other severe concurrentdisease, which, in the opinion of the investigator, would place the patient at unduerisk or interfere with the study. In particular a documented test for HIV, HBV and HCVexcluding active infection is needed.
• History within the last year of acute or subacute coronary syndromes includingmyocardial infarction, unstable or severe stable angina pectoris, inadequately treatedcardiac arrhythmias and heart insufficiency (any grade, New York Heart Association (NYHA) criteria).
• Any abnormalities observed during baseline ECG investigations that are consideredclinically 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.
• Patient requires or is taking systemic corticosteroids (>5 mg/day) or otherimmunosuppressant drugs on a long-term basis. Limited use of corticosteroids to treator prevent acute hypersensitivity reactions and asthma/COPD is not considered anexclusion 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 severeimmune suppression.
• Any conditions that in the opinion of the investigator could hamper compliance withthe study protocol.