Danilenko M, et al. - Researchers gauged whether topical targeting of tropomyosin receptor kinase (TRK) with the existing topical TRK inhibitor, pegcantratinib, 0.5% (wt/wt), is safe and efficacious in CYLD cutaneous syndrome (CCS). Findings suggested good tolerence of pegcantratinib, 0.5% (wt/wt), applied once daily and they noted that it penetrated the tumor tissue well. Nonetheless, lack of response was likely due to low tumor drug concentrations.

Methods

• Authors conducted a phase 1b open-label safety study, followed by a phase 2a within-patient randomized (by tumor), double-blind, placebo-controlled trial (the Tropomyosin Receptor Antagonism in Cylindromatosis [TRAC] trial) in a single-center trial based at a tertiary dermatogenetics referral center for CCS (Royal Victoria Infirmary, Newcastle, United Kingdom).
• Patients with germline mutations in CYLD or who satisfied clinical diagnostic criteria for CCS were recruited between March 1, 2015, and July 1, 2016.
• In phase 1b, pegcantratinib was applied by patients with CCS to a single skin tumor for 4 weeks.
• In phase 2a, the tumors were allocated to either receive active treatment on the right side and placebo on the left side (arm A) or active treatment on the left side and placebo on the right side (arm B).
• The eligibility criterion included having 10 small skin tumors with 5 matched lesions on each body side.
• Patients were randomly allocated to receive active treatment (pegcantratinib) to one body side and placebo to the other side once daily for 12 weeks.
• The number of tumors meeting the criteria for response in a prespecified critical number of pegcantratinib-treated tumors was the primary outcome measure.
• An assessment for safety of application, pain in early tumors, and compliance with the trial protocol were the secondary clinical outcome measures.

Results

• Results demonstrated that in phase 1b, eight female patients with a median age of 60 years (age range, 41-80 years) were recruited and completed the study.
• No adverse treatment site reactions were seen in any of the participants.
• Findings suggested that in treated tumors, reduced pain was reported by three patients.
• In phase 2a, vs 6 tumors treated with placebo, (15 patients [13 female; median age, 51 years], with 150 tumors), two tumors treated with pegcantratinib achieved the primary outcome measure of response.
• As per the results, the primary prespecified number of responses was not met.
• They noted a low incidence of adverse events.