Ctim-04. topical diphencyprone immunotherapy for cutaneous neurofibromas associated with nf1, a phase 1 study

Abstract Neurofibromatosis type 1 (NF1) is a tumor predisposition syndrome affecting ~1 in 2500 people. Affected patients develop peripheral nerve sheath tumors of the skin known as cutaneous neurofibromas (CN), with variable disease burden ranging from 0-1 tumors to over 10,000. Patients cite deformity, pain, and pruritus from CN as one of the most difficult features of the disease. To date, there are no practical or effective pharmacotherapies for these tumors. This is a single-center, phase I, open label trial to evaluate the safety, tolerability, and efficacy of diphencyprone (DPCP), a topical hapten compound that induces a delayed-type. Twelve adult patients with NF1 and >3 CN of maximum diameter >4 mm were enrolled. DPCP 0.04% ointment was administered topically once weekly to up to 20 cNFs in a localized body region for 10 weeks. Endpoints included (primary) safety and tolerability of DPCP ointment via CTCAE reporting and subjective scoring of symptoms. Efficacy was assessed using RECIST (Response Evaluation Criteria in Solid Tumors) guidelines in conjunction with whole body photography and manual tri-axial tumor measurements. One treated tumor is tracked throughout the study with optical coherence tomography (OCT) imaging. Skin biopsies of a CN and surrounding tissue are collected at baseline, on Day 17 after treatment initiation, and four weeks post-treatment for exploratory endpoints qRT-PCR, single-cell RNA sequencing, and immunohistochemistry to detect differences in immune cell infiltration, tumor cell density, and transcriptional changes throughout the treatment course. Clinical trial information: NCT05438290.