A Phase II Study of Intratumoral Application of L19IL2/L19TNF in Melanoma Patients in Clinical Stage III or Stage IV M1a With Presence of Injectable Cutaneous and/or Subcutaneous Lesions

Philogen S.p.A.2 sites in 1 country21 target enrollmentDecember 2012

ConditionsMalignant Melanoma, Skin

InterventionsL19IL2+L19TNF

DrugsL19IL2+L19TNF

Overview

Phase: Phase 2
Intervention: L19IL2+L19TNF
Conditions: Malignant Melanoma, Skin
Sponsor: Philogen S.p.A.
Enrollment: 21
Locations: 2
Primary Endpoint: Rate of patients with complete response (CR) of L19IL2 treated Index/Non-Index lesions at week 12.
Status: Completed
Last Updated: 10 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This Phase II study is an uncontrolled, multicenter, prospective study for patients with malignant melanoma of the skin in clinical stage III or stage IV M1a.

Twenty Patients will be treated with a mixture of L19IL2 and L19TNF once weekly for up to 4 weeks.

The dose will be distributed among the lesions via multiple intralesional injections.

The proportion of patients with complete response at week 12 will be calculated.

Detailed Description

L19IL2 is a recombinant fusion protein composed of a fully human recombinant monoclonal antibody (L19) and the human recombinant interleukin-2 (IL-2). IL2, is a potent stimulator of the immune response. It has a central role in the regulation of T cell responses and effects on other immune cells such as natural killer cells, B cells, monocyte/macrophages and neutrophils. IL2 can induce tumor regression through its ability to stimulate a potent cell-mediated immune response in vivo. L19TNF is a recombinant fusion protein composed of a fully human recombinant monoclonal antibody (L19) and the human tumor necrosis factor-alpha, a primary mediator of immune regulation and inflammation. As an anti-tumor agent, TNF exerts its major effects via a preferential toxicity for the endothelial cells of the tumor-associated vasculature and an increase of the antitumor immune response. Given at sufficient doses (e.g. intratumorally or in the ILP setting with melphalan), TNF causes significant tumor shrinkage in solid cancer subjects. This phase II signal generating study is designed to test the efficacy and safety of an intratumorally administered mixture of L19IL2 + L19TNF in patients suffering from metastatic melanoma. It is well documented that the intratumoral administration of IL-2 leads to a high response rate and unexpectedly favorable longtime outcome and several tumor responses have been observed in clinical trials of Philogen, both using intratumorally administered L19IL2 and L19TNF in the ILP setting. Preclinical data produced within the Philogen group now suggest that the intratumoral administration of a mixture of L19IL2 and L19TNF could be even more effective. After only one intratumoral administration of a mixture of L19IL2 and L19TNF tumors disappeared completely while neither L19IL2 nor L19TNF monotherapy was nearly as effective.

Registry

clinicaltrials.gov

Start Date

December 2012

End Date

May 2015

Last Updated

10 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Philogen S.p.A.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Histologically confirmed malignant melanoma of the skin in clinical stage III or stage IV M1a
•Presence of measurable and injectable cutaneous and/or subcutaneous lesions
•Males or females, age ≥ 18 years
•ECOG Performance Status/WHO Performance Status ≤ 2
•Life expectancy of at least 12 weeks
•Absolute neutrophil count \> 1.5 x 10\^9/L
•Hemoglobin \> 9.0 g/dL
•Platelets \> 100 x 10\^9/L
•Total bilirubin ≤ 30 μmol/L (or ≤ 2.0 mg/dl)
•ALT and AST ≤ 2.5 x the upper limit of normal (ULN)

Exclusion Criteria

•Uveal melanoma and mucosal melanoma
•Evidence of visceral metastases and/or active brain metastases at screening
•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) or any cancer curatively treated \< 5 years prior to study entry
•History of HIV infection or infectious hepatitis B or C
•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.
•History within the last year of acute or subacute coronary syndromes including myocardial infarction, unstable or severe autoimmune disease
•History of organ allograft or stem cell transplantation
•Recovery from major trauma including surgery within 4 weeks prior to administration of study treatment.
•Known history of allergy to IL2, TNF, or other human proteins/peptides/antibodies.
•Breast feeding female