Patients with malignant tumors of the skin amenable to intratumoral injection, and in a curative or neoadjuvant or palliative intention, including: • Basal cell carcinoma (BCC) • Cutaneous squamous cell carcinoma (cSCC) • Merkel cell carcinoma (MCC) • Keratoacanthoma (KA) • Malignant Adnexal Tumors of the skin (MATS) • Tumors from Cutaneous T-cell lymphoma (CTCL) • Kaposi’s sarcoma (KS)
Conditions
Sponsors
Philogen S.p.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patient participation to the present study is subjected to the positive evaluation of a local interdisciplinary tumor board, in the context of available treatment alternatives. Whatever the tumor (list of eligible tumors below) the local interdisciplinary tumor board has to consider that a local response to injection of L19IL2/L19TNF may be of benefit for the patient, in the context of this tumor and available therapeutic opportunities, benefit defined by any of the following objectives: (1) to avoid surgery considered difficult or mutilating or (2) as a neoadjuvant treatment with the objective to permit surgery considered initially impossible, or to facilitate surgery considered difficult or mutilating, or to secure surgery considered of uncertain effect or (3) as a salvage treatment to control a tumor proved resistant to treatment alternatives or (4) as a palliative treatment improving patient comfort. 2. Patient must have at least one skin tumor that is amenable to intratumoral injection. 3. All tumors must be histologically confirmed before treatment. 4. Tumors eligible to the present study include: o Difficult-to-treat lesions BCC: as defined by EADO operational staging system (stages IIa to IIIb) [1]. o Non-metastatic cSCC: • Either advanced SCC for which a simple surgical excision is difficult or impossible, • Or common SCC at high risk of recurrence, for which surgery alone is deemed uncertain by the tumor board, according to EADO/EORTC interdisciplinary guidelines [2]. cSCC post-transplantation, or cSCC in patients with concomitant chronic lymphocytic leukemia, or patients after anti PD-1 failure are all eligible to the study, according to the evaluation of the tumor board; o KA: particularly when surgical excision is considered as too much mutilating for this type of tumor o MCC: particularly when either primary tumor is considered unresectable, or skin metastases or local relapse are primarily or secondarily resistant to anti-PD1 (progress under anti-PD1) o CTCL: particularly when skin tumors at tumoral stage of Mycosis fungoides subtypes are resistant to usual systemic treatments o KS: Classic or endemic, histologically confirmed KS, particularly when local response can be considered of either functional or cosmetic benefit o MATS: Advanced or refractory MATS. 5. Subjects must have radiographically or clinically measurable disease, defined as at least one injectable lesion that is = 10 mm in diameter in at least 1 dimension, or an aggregate of injectable lesions that measures = 10 mm in diameter in at least 1 dimension. 6. Subjects must be able and willing to undergo serial biopsies of injected lesion(s) and, when applicable and clinically feasible, non-injected lesions. 7. Male or female patients from the age of 18 years. 8. ECOG Performance Status/WHO Performance Status = 1. 9. Hemoglobin > 10.0 g/dL. 10. Platelets > 100 x 109/L. 11. ALT and AST, GGT and Lipase = 1.5 x the upper limit of normal (ULN). 12. Serum creatinine 60 mL/min. 13. 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. 14. 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
Exclusion criteria
Exclusion criteria: 1. Previous or concurrent cancer type that is distinct from the cancers being evaluated in this study, exception made for any other cancer curatively treated = 2 years prior to study entry. 2. Previous topical or systemic chemotherapy, immunotherapy or radiation therapy at the tumor sites within 4 weeks prior to study drug administration. 3. Presence of active severe bacterial or viral infections or other severe concurrent disease, which, in the opinion of the investigator, would place the patient at undue risk or interfere with the study. In particular, a documented test for HIV, HBV, HCV and Covid-19 excluding active infection is needed. 4. Impaired cardiocirculatory functions due to any of the following conditions: a. History within the last year of acute or subacute coronary syndromes including myocardial infarction, unstable or severe stable angina pectoris. b. Inadequately controlled cardiac arrhythmias including atrial fibrillation. c. Heart insufficiency (> Grade II, New York Heart Association (NYHA) criteria). d. Any abnormalities observed during baseline ECG and Echocardiogram investigations that are considered as clinically significant by the investigator. e. Uncontrolled hypertension. f. Ischemic peripheral vascular disease (Grade IIb-IV). 5. Known arterial aneurysms. 6. INR > 3. 7. Known uncontrolled coagulopathy or bleeding disorder. 8. Known hepatic cirrhosis or severe pre-existing hepatic impairment. 9. Moderate to severe respiratory failure. 10. Active autoimmune disease. 11. Patient requires or is taking systemic corticosteroids or other immunosuppressant drugs on a long-term basis. Limited use of corticosteroids to treat or prevent acute hypersensitivity reactions and asthma/COPD is not considered an exclusion criterion. 12. Known history of allergy to IL2, TNF, or other human proteins/peptides/antibodies. 13. Pregnancy or breast-feeding. 14. Severe diabetic retinopathy. 15. Recovery from major trauma including surgery within 4 weeks prior to enrollment. 16. Patient with iatrogenic or pathologic severe immune suppression. 17. Any conditions that in the opinion of the investigator could hamper compliance with the study protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Efficacy of L19IL2/L19TNF measured as Confirmed Best Overall Response Rate BORR (Complete Response CR + Partial Response PR) for each tumor type measured according to RECIST v1.1 criteria. Confirmation of CR requires histopathological analysis of exeresis specimens for lesions removed by surgery or of biopsies in all other cases. ;Secondary Objective: Secondary objective of the study is to demonstrate the efficacy of L19IL2/L19TNF measured as: o Disease control rate DCR (Complete Response CR + Partial Response PR + Stable Disease SD) for each tumor type measured according to RECIST v1.1 criteria. o Local PFS (LPFS) on the treated tumors only, o Progression-free survival PFS, assessed separately in patients who are not resected after CR (curative intention) and in patients who undergo secondary surgery (neoadjuvant intention), whatever the RECIST response to treatment, taking into account appearance of new lesions and occurrence of metastases etc. o Among tumors not initially amenable to surgery, proportion which are finally resected or disappear. o Effect on non-treated lesions, if any o Pathological Response for each tumor type in surgical specimens from tumors which are resected after treatment, or in biopsy for the others In addition, safety of intratumoral administration of L19IL2/L19TNF will be evaluated. ;Primary end point(s): Primary endpoint is the confirmed Best Overall Response Rate BORR (Complete Response CR + Partial Response PR) for each tumor type measured according to RECIST v1.1 criteria. Confirmation of CR requires histopathological analysis of exeresis specimens for lesions removed by surgery or of biopsies in all other cases;Timepoint(s) of evaluation of this end point: End of study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints are o Disease control rate DCR (Complete Response CR + Partial Response PR + Stable Disease SD) for each tumor type measured according to RECIST v1.1 criteria. o Local PFS (LPFS) on the treated tumors only, o Progression-free survival PFS, assessed separately in patients who are not resected after CR (curative intention) and in patients who undergo secondary surgery (neoadjuvant intention), whatever the RECIST response to treatment, taking into account appearance of new lesions and occurrence of metastases etc. o Among tumors not initially amenable to surgery, proportion which are finally resected or disappear. o Effect on non-treated lesions, if any o Pathological Response for each tumor type in surgical specimens from tumors which are resected after treatment, or in biopsy for the others ;Timepoint(s) of evaluation of this end point: End of study | — |
Countries
France, Italy, Spain
Contacts
Public ContactRegulatory Department
Philogen S.p.A.
Outcome results
None listed