Phase I trial will be conducted in patients suffering local metastatic melanoma with relapsed
cutaneous/subcutaneous tumors including melanoma-in-transit. Based on the preclinical data
package, DNA Therapeutics has considered that the risk-benefit ratio of DT01 supports the
initiation of a phase I clinical study in this population. The recommended starting dose of
DT01 for the first injection to human was based on NOAELs and Maximum Recommended Starting
Dose (MRSD) calculations and by considering both local and systemic approaches. It was set at
16 mg (4 mg per injection site, 2 injections per tumor, 2 tumors to be treated). This
starting dose will be increased up to 96 mg if no DLT occurred during dose escalation.
DT01 will be locally administered by peritumoral subcutaneous and/or intratumoral injections
in combination with hypo-fractionated radiotherapy (RT) (10x 3 Gy) and chloroquine (100 mg
oral QD) starting one week before DT01 and RT treatments. DT01 will be administered 3 times a
week during two weeks; The study will be an open, non-randomised, multicentre, phase I dose
escalation (16, 32, 48, 64 and 96 mg) safety study with a 3+3 design.
The purpose of this study will be to evaluate the safety, tolerance, pharmacokinetics of DT01
in association with palliative radiotherapy and to evaluate pharmacodynamics and the
anti-tumor activity of DT01 according to RECIST criteria on day 26, 40 and 54. The duration
of response (Time-To-Local Recurrence, TTLR), will be monitored 3, 6, 9 and 12 months after
the beginning of the DT01 treatment.