ONFEKAFUSP ALFA for Basal cell carcinoma | Cutaneous squamous cell carcinoma | Merkel cell carcinoma | Keratoacanthoma | Malignant adnexal tumor of the skin | Cutaneous T-cell lymphoma | Kaposi sarcoma

Inclusion criteria

• {"criterion_text":"- 1.\tPatient 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.\n- 10.\tPlatelets > 100 x 109/L.\n- 11.\tALT and AST, GGT and Lipase ≤ 1.5 x the upper limit of normal (ULN).\n- 12.\tSerum creatinine < 1.5 x ULN and GFR > 60 mL/min.\n- 13.\tAll 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.\n- 14.\tA woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. 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, vasectomised partner. For any other recommendation patient should follow the Contraception Guidance 2014_09_HMA_CTFG_Contraception_guidance Version 1.1.\n- 15.\tMale 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.\n- 16.\tWillingness and ability to comply with the scheduled visits, treatment plan, laboratory tests and other study procedures.\n- 2.\tPatient must have at least one skin tumor that is amenable to intratumoral injection.\n- 3.\tAll tumors must be histologically confirmed before treatment.\n- 4.\tPatients with skin tumors eligible to the present study include: o\tBCC 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\tNon-metastatic cSCC patients: •\teither advanced SCC for which a simple surgical excision is difficult or impossible, or •\tcommon 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\tKA: particularly when surgical excision is considered as too much mutilating for this type of tumor. o\tMCC: 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\tCTCL: Tumoral stage of Mycosis fungoides subtypes which are resistant to usual systemic treatments. In order to validate the first inclusion criterion of this trial, the tumor board will take into account that the treatment under investigation is intended to be only a palliative local therapy and cannot compete with a general efficacious strategy, if any. o\tKS: Classic or endemic, histologically confirmed KS, particularly when local response can be considered of either functional or cosmetic benefit. In order to validate the first inclusion criterion of this trial, the tumor board will take into account that the treatment under investigation is intended to be only a palliative local therapy and cannot compete with a general efficacious strategy, if any. o\tMATS: Advanced or refractory MATS.\n- 5.\tSubjects 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.\n- 6.\tSubjects must be able and willing to undergo serial biopsies of injected lesion(s) and, when applicable and clinically feasible, non-injected lesions.\n- 7.\tMale or female patients from the age of 18 years\n- 8.\tECOG Performance Status/WHO Performance Status ≤ 1.\n- 9.\tHemoglobin > 10.0 g/dL."}

Exclusion criteria

• {"criterion_text":"- 1.\tPrevious 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\n- 10.\tActive autoimmune disease.\n- 11.\tPatient 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.\n- 12.\tKnown history of allergy to IL2, TNF, or other human proteins/peptides/antibodies.\n- 13.\tPregnancy or breast-feeding.\n- 14.\tSevere diabetic retinopathy.\n- 15.\tRecovery from major trauma including surgery within 4 weeks prior to enrollment\n- 16.\tPatient with iatrogenic or pathologic severe immune suppression.\n- 17.\tAny conditions that in the opinion of the investigator could hamper compliance with the study protocol.\n- 18.\tAny known hypersensitivity to the constituents of the vehicle L19IL2 and L19TNF.\n- 2.\tPrevious topical or systemic chemotherapy, immunotherapy, or radiation therapy at the tumor sites within 4 weeks prior to study drug administration.\n- 3.\tPresence 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.\n- 4.\tImpaired cardiocirculatory functions due to any of the following conditions: a.\tHistory within the last year of acute or subacute coronary syndromes including myocardial infarction, unstable or severe stable angina pectoris. b.\tInadequately controlled cardiac arrhythmias including atrial fibrillation. c.\tHeart insufficiency (> Grade II, New York Heart Association (NYHA) criteria). d.\tAny abnormalities observed during baseline ECG and Echocardiogram investigations that are considered as clinically significant by the investigator. e.\tUncontrolled hypertension. f.\tIschemic peripheral vascular disease (Grade IIb-IV).\n- 5.\tKnown arterial aneurysms\n- 6.\tINR > 3.\n- 7.\tKnown uncontrolled coagulopathy or bleeding disorder.\n- 8.\tKnown hepatic cirrhosis or severe pre-existing hepatic impairment.\n- 9.\tModerate to severe respiratory failure"}

Primary endpoints

• {"endpoint_text":"- •\tEfficacy of L19IL2/L19TNF measured as: o\tConfirmed 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.","definition_or_measurement_approach":"Measured according to RECIST v1.1 criteria. Confirmation of Complete Response (CR) requires histopathological analysis of exeresis specimens for surgically removed lesions or biopsies in other cases."}

Secondary endpoints

• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Measured according to RECIST v1.1 criteria (DCR = CR + PR + SD)."}
• {"endpoint_text":"- Efficacy of L19IL2/L19TNF measured as: Local progression free survival (LPFS) on the treated tumors only.","definition_or_measurement_approach":"Local progression-free survival assessed on treated tumors only."}
• {"endpoint_text":"- Efficacy of L19IL2/L19TNF measured as: Progression-free survival (PFS), assessed separately in patients who are not resected after 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.","definition_or_measurement_approach":"PFS assessed separately for non-resected patients and those undergoing secondary surgery; considers new lesions and metastases."}
• {"endpoint_text":"- Efficacy of L19IL2/L19TNF measured as: Among tumors not initially amenable to surgery, a proportion which are finally resected or disappear.","definition_or_measurement_approach":"Proportion of tumors initially not amenable to surgery that are ultimately resected or disappear."}
• {"endpoint_text":"- Efficacy of L19IL2/L19TNF measured as: Effect on non-treated lesions, if any.","definition_or_measurement_approach":"Assessment of response in non-injected/non-treated lesions (if any effect observed)."}
• {"endpoint_text":"- Efficacy of L19IL2/L19TNF measured as: Pathological response for each tumor type in surgical specimens from tumors which are resected after treatment, or in biopsy for the other types.","definition_or_measurement_approach":"Pathological response assessed on surgical specimens or biopsies post-treatment."}
• {"endpoint_text":"- Safety of intratumoral administration of L19IL2/L19TNF.","definition_or_measurement_approach":"Safety assessed via adverse event reporting and clinical/laboratory monitoring (as per protocol)."}

France

Earliest CTIS Part Ii Submission Date

22-10-2024

Latest Decision Or Authorization Date

10-03-2026

Processing Time Days

504

Number Of Sites

3

Number Of Participants

5

Spain

Earliest CTIS Part Ii Submission Date

22-10-2024

Latest Decision Or Authorization Date

16-03-2026

Processing Time Days

510

Number Of Sites

3

Number Of Participants

5

Italy

Earliest CTIS Part Ii Submission Date

22-10-2024

Latest Decision Or Authorization Date

16-03-2026

Processing Time Days

510

Number Of Sites

9

Number Of Participants

16

Primary sponsor

Full Name

Philogen S.p.A.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Italy