BIFIKAFUSP ALFA for Malignant melanoma | Malignant melanoma stage III

Inclusion criteria

• {"criterion_text":"- Diagnosis of malignant melanoma of the skin with locally advanced disease as defined by clinical stage III B and III C according to AJCC 7th Ed., eligible for complete surgical resection"}
• {"criterion_text":"- Total bilirubin ≤ 30 μmol/L (or ≤ 2.0 mg/dl)"}
• {"criterion_text":"- ALT and AST ≤ 2.5 x the upper limit of normal (ULN)"}
• {"criterion_text":"- Serum creatinine < 1.5 x ULN"}
• {"criterion_text":"- LDH serum level ≤ 1.5 x ULN"}
• {"criterion_text":"- Documented negative test for HIV, HBV and HCV. For HBV serology, the determination of HBsAg and anti-HBcAg Ab is required. In patients with serology documenting previous exposure to HBV (e.g., anti-HBsAg and/or anti-HBc Ab) negative serum HBV-DNA is also required"}
• {"criterion_text":"- 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) (v4.03) Grade ≤ 1 unless otherwise specified above"}
• {"criterion_text":"- Negative pregnancy test at screening for Women Of Childbearing Potential (WOCBP*). Pregnant women are not allowed to participate to this study. WOCBP must be using, from the 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, vasectomized partner or sexual abstinence. Pregnancy test will be repeated at the Safety Visit (only WOCBP and only for patients in Arm 1). Women of childbearing potential are defined as females who have experienced menarche, are not postmenopausal (12 months with no menses without an alternative medical cause) and are not permanently sterilized (e.g., tubal occlusion, hysterectomy, bilateral oophorectomy or bilateral salpingectomy)."}
• {"criterion_text":"- Male 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"}
• {"criterion_text":"- Evidence of a personally signed and dated informed consent document indicating that the subject has been informed of all pertinent aspects of the study"}
• {"criterion_text":"- Willingness and ability to comply with the scheduled visits, treatment plan, laboratory tests and other study procedures"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Prior anti-tumor treatment for the primary melanoma lesion, including surgery and approved adjuvant treatments (e.g., radiotherapy, immune checkpoint inhibitors, BRAF/MEK inhibitors, etc.) is allowed"}
• {"criterion_text":"- Males or females, age ≥ 18 years"}
• {"criterion_text":"- ECOG Performance Status/WHO Performance Status ≤ 1"}
• {"criterion_text":"- Life expectancy of at least 24 months"}
• {"criterion_text":"- Absolute neutrophil count > 1.5 x 109/L"}
• {"criterion_text":"- Hemoglobin > 9.0 g/dL"}
• {"criterion_text":"- Platelets > 100 x 109/L"}

Exclusion criteria

• {"criterion_text":"- Uveal melanoma, mucosal melanoma or melanoma with unknown primary"}
• {"criterion_text":"- Ischemic peripheral vascular disease (Grade IIb-IV)"}
• {"criterion_text":"- Severe diabetic retinopathy"}
• {"criterion_text":"- Active autoimmune disease"}
• {"criterion_text":"- History of organ allograft or stem cell transplantation"}
• {"criterion_text":"- Recovery from major trauma including surgery within 4 weeks prior to enrollment"}
• {"criterion_text":"- Known history of allergy to IL2, TNF, or other human proteins/peptides/antibodies or any other constituent of the product"}
• {"criterion_text":"- Breast feeding female"}
• {"criterion_text":"- Anti-tumor therapy (except allowed treatments listed at point 3 of Inclusion criteria) within 4 weeks before enrollment"}
• {"criterion_text":"- Previous in vivo exposure to monoclonal antibodies for biological therapy (except allowed treatments listed at point 3 of Inclusion criteria) in the 6 weeks before enrollment"}
• {"criterion_text":"- Planned administration of growth factors or immunomodulatory agents (except allowed treatments listed at point 3 of Inclusion criteria) within 7 days before enrollment"}
• {"criterion_text":"- Evidence of distant metastases at screening"}
• {"criterion_text":"- Patient requiring or 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"}
• {"criterion_text":"- Any conditions that in the opinion of the investigator could hamper compliance with the study protocol"}
• {"criterion_text":"- Previous enrolment and randomization in this same study"}
• {"criterion_text":"- 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 & T1), second primary melanoma in situ or any cancer curatively treated ≥ 5 years prior to study entry"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- History within the last year of acute or subacute coronary syndromes including myocardial infarction, unstable or severe stable angina pectoris"}
• {"criterion_text":"- Inadequately controlled cardiac arrhythmias including atrial fibrillation"}
• {"criterion_text":"- Heart insufficiency (> Grade II, New York Heart Association (NYHA) criteria)"}
• {"criterion_text":"- LVEF ≤ 50% and/or abnormalities observed during baseline ECG and Echocardiogram investigations that are considered as clinically significant by the investigator"}
• {"criterion_text":"- Uncontrolled hypertension"}

Primary endpoints

• {"endpoint_text":"- Recurrence-free survival (RFS) in the treatment arm (L19IL2/L19TNF plus surgery; Arm 1) versus control arm (Arm 2)","definition_or_measurement_approach":""}

Secondary endpoints

• {"endpoint_text":"- Overall survival (OS) in the treatment arm (L19IL2/L19TNF plus surgery; Arm 1) versus control arm (surgery; Arm 2)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Local recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS) in the treatment arm (L19IL2/L19TNF plus surgery - Arm 1) versus control arm (Arm 2)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Proportion of patients with pathological responses (defined as the proportion of patients with a pathological CR, pathological near-CR, or pathological PR)","definition_or_measurement_approach":"Defined as the proportion of patients with a pathological Complete Response, pathological near-Complete Response, or pathological Partial Response assessed on the surgical specimen after tumor removal (applies to patients in Arm 1 only)."}
• {"endpoint_text":"- Safety of intratumoral administration of L19IL2/L19TNF","definition_or_measurement_approach":""}
• {"endpoint_text":"- 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; the data will be collected for at least 50 patients). Study of blood biomarkers","definition_or_measurement_approach":"Immunophenotypic characterisation of PBMCs for changes in absolute counts and relative percentages of lymphocytic subpopulations over time; biomarker sampling limited to patients recruited in German centres, target ≥50 patients."}
• {"endpoint_text":"- Assessment of the formation of human anti-fusion protein antibodies (HAFA) against L19IL2 and L19TNF","definition_or_measurement_approach":""}

Germany

Earliest CTIS Part Ii Submission Date

25-07-2024

Latest Decision Or Authorization Date

31-07-2024

Processing Time Days

6

Number Of Sites

10

Number Of Participants

185

Italy

Earliest CTIS Part Ii Submission Date

25-07-2024

Latest Decision Or Authorization Date

12-08-2024

Processing Time Days

18

Number Of Sites

7

Number Of Participants

34

France

Earliest CTIS Part Ii Submission Date

25-07-2024

Latest Decision Or Authorization Date

05-08-2024

Processing Time Days

11

Number Of Sites

3

Number Of Participants

17

Poland

Earliest CTIS Part Ii Submission Date

02-08-2024

Latest Decision Or Authorization Date

29-08-2024

Processing Time Days

27

Number Of Sites

2

Number Of Participants

20

Primary sponsor

Full Name

Philogen S.p.A.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Italy

Contract research organisations

Name

Pharmtrace klinische Entwicklung GmbH

Responsibilities

code:5

Name

Envestia Limited

Responsibilities

code:12

Name

MONIPOL Deutschland GmbH

Responsibilities

code:1

Third parties

• {"country":"Germany","full_name":"Cogitars GmbH","duties_or_roles":"code:10","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Envestia Limited","duties_or_roles":"code:12","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"MONIPOL Deutschland GmbH","duties_or_roles":"code:1","organisation_type":"Pharmaceutical company"}
• {"country":"Poland","full_name":"Monipol Polska Sp. z o.o.","duties_or_roles":"code:1","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Pharmtrace klinische Entwicklung GmbH","duties_or_roles":"code:5","organisation_type":"Pharmaceutical company"}
• {"country":"Italy","full_name":"Pharma Quality Europe S.r.l.","duties_or_roles":"code:11, code:8","organisation_type":"Pharmaceutical company"}