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) MedDRA version: 21.1 Level: LLT Classification code 10007116 Term: Cancer of skin (excl melanoma) System Orga
Conditions
Interventions
Product Name: L19TNF
Product Code: [L19TNF]
Pharmaceutical Form: Solution for injection/infusion
INN or Proposed INN: Onfekafusp alfa
CAS Number: 1957239-88-1
Current Sponsor code: L19TNF
Other descri
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 (list of eligible tumors below).. 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. Patients with skin tumors eligible to the present study include: o BCC patients with difficult-to-treat lesions: as defined by EADO operational staging system (stages IIa to IIIb) [1]. Patients must either(i) have already received, or (ii) have progressed after, or (iii) be resistant to, or (iv) not be candidate to all possible alternative treatments, including notably use or re-use of surgery, radiotherapy, hedgehog inhibitors. o Non-metastatic cSCC patients: • 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]. Patients must either (i) have already received, or (ii) have progressed after, or (iii) be resistant to, or (iv) not be candidate to all possible alternative treatments, including notably use or re-use of surgery, radiotherapy, cetuximab and/or other anti-PD1 checkpoint inhibitors. 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). Patients must either (i) have already received, or (ii) have progressed after, or (iii) be resistant to, or (iv) not be candidate to all possible alternative treatments, including notably use or re-use of surgery, radiotherapy, and/or any anti-PD1 checkpoint inhibitors. o CTCL: Tumoral stage of Mycosis fungoides subtypes which are resistant to usual systemic treatments. therapy and cannot compete with a general efficacious strategy, if any. 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, noninjected 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 of any prior therapy must have resolved 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. 15. Male patients with WOCBP partners must agree to use simultaneously two acceptable methods of contraceptionfrom the screening to three months following the last study drug administration. 16. Willing
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. Patients suffering from cSCC post-organ transplantation, or cSCC patients with concomitant chronic lymphocytic leukemia are excluded from the study. 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: - Disease control rate DCR (Complete Response CR + Partial Response PR + Stable Disease SD) for each tumor type measured according to RECIST v1.1 criteria. - 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. - Among tumors not initially amenable to surgery, proportion which are finally resected or disappear. - Effect on non-treated lesions, if any - 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 (EOS) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 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 | — |
Countries
France, Italy, Spain
Contacts
Public ContactRegulatory Department
Philogen S.p.A.
Outcome results
None listed