L19IL2/L19TNF in Skin Cancer Patients

Phase II, open label, multicentric, proof-of-principle basket trial in patients with malignant tumors of the skin amenable to intratumoral injection, and in a curative or neoadjuvant or palliative intention.

In the study, 70 patients will be enrolled and treated with a mixture of L19IL2 and L19TNF once weekly for 4 consecutive weeks. The total dose/volume will be distributed among the target lesions defined at screening via single or multiple intralesional injections, according to lesions' size and number.

Tumor assessment:

• Tumor assessment (TA) visits will be performed at Week 12 (Day 78 from the beginning of treatment), then every 8 weeks and up to Week 52 after beginning of treatment. For confirmation of objective responses, unscheduled visits will be performed 4 weeks after the visit, which the objective response was first recorded at.
• During each TA visit, measurement of tumor lesions and documentation (photographic documentation with use of a caliper for cutaneous lesions; ultrasound for subcutaneous lesions; imaging techniques as deemed appropriate/necessary by treating physician) will be performed. The choice of the most suitable instrumental technique to measure and document evolution of the disease will be made by the treating physician at baseline screening, the same technique will have to be used for all following tumor assessments.
• Histological assessment of tumor tissue: estimation of percent of residual viable tumor cells and tumor infiltration with immune responsive cell. Locally performed histological specimen assessment will be centrally reviewed.

After confirmed partial responses, surgery with curative intent is allowed (if considered feasible and of potential benefit for the patients by the treating physician) and will be performed no later than 4 weeks after the TA visit at which the partial response is confirmed.

Safety assessment:

• The safety profile of intratumoral administration of L19IL2/L19TNF will be assessed throughout the study. A complete safety assessment will be performed at the safety visit.

Human-anti-fusion protein antibodies (HAFA) assessment:

• The possible development of antibodies against L19IL2 or L19TNF will be verified. Samples will be collected before L19IL2/L19TNF administration at Days 1, 22 and Day 78 (TA visit).

A Data and Safety Monitoring Board (DSMB), composed of expert dermato-oncologists, will evaluate safety and efficacy data after the first 20 patients and will formulate recommendations for the prosecution of the study.