Patients with high-risk, locally advanced (non-metastatic, node negative, single or multifocal), basal cell carcinoma (BCC) or cutaneous squamous cell carcinoma (cSCC) amenable to intratumoral injection, not eligible to surgery according to the evaluation of a local interdisciplinary tumor board or who refuse surgery and for whom an histological evaluation is available according to international guidelines MedDRA version: 20.0 Level: PT Classification code 10004146 Term: Basal cell carcinoma S
Conditions
Sponsors
Philogen S.p.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients with high-risk, locally advanced (non-metastatic, node negative, single or multifocal), basal cell carcinoma (BCC) or cutaneous squamous cell carcinoma (cSCC) amenable to intratumoral injection, not eligible to surgery or radiation therapy according to the evaluation of a local interdisciplinary tumor board or who refuse surgery or radiation therapy and for whom an histological evaluation is available according to international guidelines. Eligible patients are those as defined by the European Association of Dermato-Oncology (EADO) operational staging system (stages IIa to IIIb) [1] for BCC and by EADO/EORTC (European Organization for Research and Treatment of Cancer) interdisciplinary guidelines [1] for cSCC. 2. Patients with injectable and measurable regional cutaneous or subcutaneous in-transit or satellite metastasis but without regional nodal involvement are also eligible. 3. Male or female patients, age 18 - 100 years. 4. ECOG Performance Status/WHO Performance Status = 1. 5. Hemoglobin > 10.0 g/dL. 6. Platelets > 100 x 109/L. 7. ALT and AST, GGT and Lipase = 1.5 x the upper limit of normal (ULN). 8. Serum creatinine =65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: 1. Previous or concurrent cancer type that is distinct from the cancers being evaluated in this study, except any cancer curatively treated more than 2 years prior to study entry. 2. Topical or systemic chemotherapy, immunotherapy or radiation therapy on the tumor sites in the 4 weeks prior to study drug administration. 3. Patients with node positive BCC/cSCC who are candidate to SHH inhibitor or checkpoint inhibitor therapy. 4. 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 and HCV excluding active infection is needed. 5. History within the last year of acute or subacute coronary syndromes including myocardial infarction, unstable or severe stable angina pectoris, of inadequately treated cardiac arrhythmias and heart insufficiency (any grade, New York Heart Association (NYHA) criteria). 6. Any abnormalities observed during baseline ECG investigations that are considered as clinically significant by the investigator. 7. Known arterial aneurysms. 8. INR > 3. 9. Uncontrolled hypertension. 10. Known uncontrolled coagulopathy or bleeding disorder. 11. Known hepatic cirrhosis or severe pre-existing hepatic impairment. 12. Moderate to severe respiratory failure. 13. Active autoimmune disease. 14. Patient requires or is taking systemic corticosteroids (>5 mg/day) 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. 15. Known history of allergy to IL2, TNF, or other human proteins/peptides/antibodies. 16. Pregnancy or breast-feeding. 17. Ischemic peripheral vascular disease (Grade IIb-IV). 18. Severe diabeticretinopathy. 19. Recovery from major trauma including surgery within 4 weeks prior to enrollment. 20. Solid organ transplant recipient or patient with iatrogenic or pathologic severe immune suppression. 21. Any conditions that in the opinion of the investigator could hamper compliance with the study protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Confirmed Best Overall Response Rate (BORR) [Complete Response (CR) + Partial Response (PR)] for BCC tumor type measured according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. Confirmation of CR requires histopathological analysis of excision specimens for surgically removed lesions or biopsies in all other cases.;Secondary Objective: oDisease Control Rate (DCR) [Complete Response (CR) + Partial Response (PR) + Stable Disease (SD)] for each tumor type measured according to RECIST v1.1 criteria. oProgression-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. oPathological response for each tumour type in tissue samples taken from surgically resected tumours or in bioptic samples taken at the end of treatment. ;Primary end point(s): Confirmed Best Overall Response Rate – BORR [Complete Response (CR) + Partial Response (PR)] for BCC according to RECIST v1.1 criteria.;Timepoint(s) of evaluation of this end point: Any of the Tumor Assessment Visits and confirmed during an unscheduled visit 4 weeks later | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Efficacy: 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 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. o Pathological Response for each tumor type in surgical specimens from tumors which are resected after treatment, or in biopsy for the other types. • Safety of intratumoral administration of L19IL2/L19TNF.;Timepoint(s) of evaluation of this end point: Any of the Tumor Assessment Visits and confirmed during an unscheduled visit 4 weeks later | — |
Countries
Germany, Poland, Switzerland
Contacts
Public ContactRegulatory Department
Philogen S.p.A.
Outcome results
None listed