Phase 1 Evaluation of Intralesionally Injected TLR9-agonist PF-3512676 in Patients With Basal Cell Carcinoma or Metastatic Melanoma

• DOI: 10.1097/cji.0b013e318174a4df
• Publication Date: 2008-05-20T07:04:36Z
• Authors: Maja A. Hofmann; Christian Kors; Heike Audring; Peter Walden; Wolfram Sterry; Uwe Trefzer
• Keywords: Tolerability; Erythema

Synthetic oligodeoxynucleotides (ODNs), such as PF-3512676, that contain unmethylated cytosine-guanine motifs (CpG ODN) have been identified highly potent immune activators by in vitro examinations and murine models. CpG ODNs induce innate adaptive responses triggering Toll-like receptor 9 expressed human B cells plasmacytoid dendritic cells. A phase 1 study was initiated to investigate safety, tolerability, serum cytokine levels, cellular responses, clinical activity of intralesional treatment with PF-3512676 patients basal cell carcinoma (BCC) or cutaneous subcutaneous melanoma metastases. Intrapatient escalating doses (up 10 mg) were injected intralesionally every 14 days 5 BCC metastases melanoma. well tolerated. Local swelling erythema occurred at the injection site 9/10 patients. There only incidence a grade III hematologic adverse event (lymphocytopenia). tumor regressions observed (1 complete regression, 4 partial regressions) metastatic regression). After interleukin-6 increased all patients, interferon-γ induced protein-10 8/10 interleukin-12p40 7/10 necrosis factor-α levels 6/10 All had biopsies; moderate abundant infiltrates lymphocytes found posttreatment most lesions both histologic types. Intralesional skin tumors safe Despite relatively low dosage, demonstrated lesions.