A Phase 2 Study of Intratumoral Administration of L19IL2/L19TNF in Locally Advanced Basal Cell Carcinoma Patients Progressing or Intolerant to Systemic Treatment.
Open-label, single-arm, multicentre study in patients with locally advanced BCC amenable to intratumoral injection, who have progressed on or are intolerant to systemic therapy as determined by a local multidisciplinary tumor board. The primary objective of the study is to evaluate the activity of intratumoral L19IL2/L19TNF, while the secondary objective is to assess the safety and efficacy. The patients will receive multiple intratumoral administrations of combined L19IL2 and L19TNF to all injectable cutaneous and subcutaneous lesions once weekly for up to 4 weeks: for those who have a partial response or stable disease as their best response, a second 4-week course L19IL2/L19TNF of four weekly injections may be administered as per treating physician judgement. Patients will be followed for a maximum of 160 weeks after beginning of treatment.
• Patients must have histologically documented, locally advanced BCC.
• Patients must have at least one injectable and measurable cutaneous or subcutaneous lesion.
• Patients must have locally advanced BCC that has progressed on or cannot tolerate HHIs and anti-PD1 treatments assessed by a local multidisciplinary tumor board.
• Patients with nodal, regional or in transit injectable BCC lesions.
• Patients must be willing to provide tissue from a core or excisional biopsy of a tumor lesion at screening and for confirmation of Objective Response or Stable Disease.
• Prior radiotherapy to the target lesions must be completed at least 4 weeks prior to first study drug administration, with all acute RT-related toxicities resolved to ≤ Grade 1
• Male or female patients, who are capable of giving consent, age ≥ 18 years.
• ECOG Performance Status/WHO Performance Status ≤ 2.
• Hemoglobin \> 10.0 g/dL.
• Platelets \> 100 x 109/L.
• ALT and AST, GGT and Lipase ≤ 1.5 x the upper limit of normal (ULN).
• 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.