Malignant melanoma of the skin in subjects with completely resectable stage IIIB and IIIC disease and presence of injectable cutaneous and/or subcutaneous or nodal lesions. MedDRA version: 20.0 Level: PT Classification code 10025670 Term: Malignant melanoma stage III System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Philogen S.p.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion criteria: 1. Diagnosis of malignant melanoma of the skin in clinical stage III B and III C, eligible for complete surgical resection. 2. Eligible subjects must have measurable disease and must be candidate for intralesional therapy with at least one injectable cutaneous, subcutaneous, or nodal melanoma lesion (= 10 mm in longest diameter) or with multiple injectable lesions that in aggregate have a longest diameter of = 10 mm. 3. Males or females, age = 18 years 4. ECOG Performance Status/WHO Performance Status = 1 5. Life expectancy of at least 24 months (see paragraph 6.3.1) 6. Absolute neutrophil count > 1.5 x 109/L 7. Hemoglobin > 9.0 g/dL 8. Platelets > 100 x 109/L 9. Total bilirubin = 30 µmol/L (or = 2.0 mg/dl) 10. ALT and AST = 2.5 x the upper limit of normal (ULN) 11. Serum creatinine =65 years) yes F.1.3.1 Number of subjects for this age range 94
Exclusion criteria
Exclusion criteria: Patients exclusion criteria: 1. Uveal melanoma and mucosal melanoma 2. Evidence of distant metastases at screening 3. Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study except cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (TA, Tis & Ti), second primary melanoma in situ or any cancer curatively treated = 5 years prior to study entry 4. Presence of active infections (e.g. requiring antimicrobial therapy) or other severe concurrent disease, which, in the opinion of the investigator, would place the patient at undue risk or interfere with the study. 5. History within the last year of acute or subacute coronary syndromes including myocardial infarction, unstable or severe stable angina pectoris. 6. Inadequately controlled cardiac arrhythmias including atrial fibrillation 7. Heart insufficiency (> Grade II, New York Heart Association (NYHA) criteria) 8. LVEF = 50% and/or abnormalities observed during baseline ECG and Echocardiogram investigations that are considered as clinically significant by the investigator. 9. Uncontrolled hypertension 10. Ischemic peripheral vascular disease (Grade IIb-IV) 11. Severe diabetic retinopathy 12. Active autoimmune disease 13. History of organ allograft or stem cell transplantation 14. Recovery from major trauma including surgery within 4 weeks prior to enrollment. 15. Known history of allergy to IL2, TNF, or other human proteins/peptides/antibodies or any other constituent of the product. 16. Breast feeding female 17. Anti-tumor therapy (except small surgery) within 4 weeks before enrollment 18. Previous in vivo exposure to monoclonal antibodies for biological therapy in the 6 weeks before enrollment 19. Planned administration of growth factors or immunomodulatory agents within 7 days before enrollment 20. Patient requires or is taking corticosteroids or other immunosuppressant drugs on a long-term basis. Limited use of corticosteroids to treat or prevent acute hypersensitivity reactions is not considered an exclusion criterion. 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: Efficacy of L19IL2/L19TNF measured as recurrence-free survival (RFS) rate in the L19IL2/L19TNF plus surgery treatment group (Arm 1) versus surgery alone (Arm 2), assessed at 1 year after randomization ;Secondary Objective: Efficacy of L19IL2/L19TNF as: - Local recurrence-free survival (LRFS) rate and distant metastasis-free survival (DMFS) rate in the L19IL2/L19TNF plus surgery treatment group (Arm 1) versus surgery alone (Arm 2), assessed at 1 y after randomization. - LRFS rate and DMFS rate in the L19IL2/L19TNF plus surgery treatment group (Arm 1) versus surgery alone (Arm 2), assessed at 1 y after surgery (for both arms). - RFS rate in the L19IL2/L19TNF plus surgery treatment group (Arm 1) versus Arm 2, assessed at 2-y and 3-y after randomization. - Overall survival (OS) in Arm 1 vs Arm 2, assessed at 1y after randomization and at 2y and 3y after randomization. - Safety of intratumoral administration of L19IL2/L19TNF - Biomarker studies: immunophenotyping of PBMCs for changes in absolute counts and relative percentages of lymphocytic subpopulations over time. Study of blood biomarkers - Assessment of the formation of human anti-fusion protein antibodies (HAFA) against L19IL2 and L19TNF ;Primary end point(s): Efficacy of L19IL2/L19TNF measured as recurrence-free survival (RFS) rate in the L19IL2/L19TNF plus surgery treatment group (Arm 1) versus surgery alone (Arm 2), assessed at 1 year after randomization. ;Timepoint(s) of evaluation of this end point: RFS rate in the L19IL2/L19TNF plus surgery treatment group (Arm 1) versus surgery alone (Arm 2), assessed at 1 year after randomization. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Efficacy of L19IL2/L19TNF: --> Local recurrence-free survival (LRFS) rate and distant metastasis-free survival (DMFS) rate in the L19IL2/L19TNF plus surgery treatment group (Arm 1) versus surgery alone (Arm 2), assessed at 1 year after randomization. --> Local recurrence-free survival (LRFS) rate and distant metastasis-free survival (DMFS) rate in the L19IL2/L19TNF plus surgery treatment group (Arm 1) versus surgery alone (Arm 2), assessed at 1 year after surgery (for both arms). ---> Recurrence-free survival (RFS) rate in the L19IL2/L19TNF plus surgery treatment group (Arm 1) versus surgery alone (Arm 2), assessed at 2-y and 3-y after randomization. - Overall survival (OS) in the L19IL2/L19TNF plus surgery treatment group (Arm 1) versus surgery alone (Arm 2), assessed at 1 year after randomization and at 2-y and 3-y after randomization. - Safety of intratumoral administration of L19IL2/L19TNF - Biomarker studies (both Arms): immunophenotypic characterization of PBMCs for changes in absolute counts and relative percentages of lymphocytic subpopulations (e.g., Tregs, MDSCs etc.) over time (only for patients recruited in German centers) . Study of blood biomarkers (e.g., S100b, LDH ratio etc.) - Assessment of the formation of human anti-fusion protein antibodies (HAFA) against L19IL2 and L19TNF.;Timepoint(s) of evaluation of this end point: - LRFS rate and DMFS rate in Arm 1 vs Arm 2, assessed at 1 y after randomization. - LRFS rate and DMFS rate in Arm 1vs Arm 2, assessed at 1 y after surgery (both arms). - Recurrence-free survival (RFS) rate in Arm 1 vs Arm 2, assessed at 2y and 3y after randomization. - Overall survival (OS) in Arm 1 versus Arm 2, assessed at 1y after randomization and at 2y and 3y after randomization. - Safety of intratumoral administration of L19IL2/L19TNF - Biomarker studies: immunophenotyping of PBMCs for changes in absolute counts and relative percentages of lymphocytic subpopulations over time. Study of blood bi | — |
Countries
France, Germany, Italy, Poland
Contacts
Public ContactRegulatory Department
Philogen S.p.A.
Outcome results
None listed