A Phase II Study of Intratumoral Administration of L19IL2/L19TNF in Non-melanoma Skin Cancer Patients With Presence of Injectable Lesions
This clinical phase II study is designed to investigate the efficacy of intratumorally administered L19IL2/L19TNF in patients with injectable lesions of BCC or cSCC. Favorable tumor responses following intralesional treatment with L19IL2/L19TNF have been observed in patients with injectable melanoma lesions of stage III or IV, for injected and non-injected lesions. The proposed clinical phase II study plans to investigate the intralesional administration of 6.5 Mio IU of L19IL2 (\ 1.08 mg) and 200 µg of L19TNF to be administered in an approximate volume of 1.0 mL as a single or multiple intratumoral injections in patients with high-risk BCC or cSCC. There is a high medical need for non-invasive therapeutic strategies with a comparable good response rate and high recurrence free survival for treatment of patients with BCC or cSCC, who cannot be treated by or refuse surgery. Surgery is not always applicable, as it may not be feasible due to the anatomic location, may have a poor cosmetic outcome for the patient or is generally not accepted as treatment strategy by the patient. However, current non-surgical treatment strategies have a considerably reduced response rate and recurrence free survival. Based on the favorable results for injected and non-injected lesions obtained in the phase II study of L19IL2/L19TNF and the good safety profile seen in the subsequent phase III study, both in stage III or IV melanoma patients, we believe, that patients with BCC or cSCC will profit from intralesional treatment with L19IL2/L19TNF.
• High-risk, localized (non-metastatic, node negative, single or multifocal) BCC or cSCC amenable to intratumoral injection.
• Patients with injectable and measurable regional cutaneous or subcutaneous in-transit or satellite metastasis but without regional nodal involvement are also eligible.
• Male or female patients, age 18 - 100 years.
• ECOG Performance Status/WHO Performance Status ≤ 1.
• Hemoglobin \> 10.0 g/dL.
• Platelets \> 100 x 10\^9/L.
• ALT and AST, GGT and Lipase ≤ 1.5 x the upper limit of normal (ULN).
• Serum creatinine \< 1.5 x ULN and GFR \> 60 mL/min.
• 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 v. 5.0) Grade ≤ 1 unless otherwise specified.
• Women of childbearing potential (WOCBP) must have negative pregnancy test results at screening. WOCBP must be using, from 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, vasectomised partner.
• 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.
• Willingness and ability to comply with the scheduled visits, treatment plan, laboratory tests and other study procedures.