DNA Therapeutics presents encouraging results for first-in-class pan DNA repair inhibitor
The trial consisted of 23 patients with melanoma skin metastasis, recruited across seven centers in France. All patients followed a two-week treatment plan and were evaluable for safety and pharmacokinetics. 21 patients were evaluable for efficacy on 76 irradiated lesions of which 41 were injected with DT01. No dose-limiting toxicity was observed. The most frequent adverse events were reversible grade 1 and 2 injection site reactions. Pharmacokinetics analyses demonstrated a systemic passage of DT01. Objective responses were observed in 51 lesions (67%), including 23 complete responses (30%). The overall response rate was correlated with DT01 systemic exposure in the subgroup of lesions that were not directly injected with DT01, suggesting a systemic effect.
Cancer cells can easily repair themselves after damage incurred in their DNA from conventional therapies such as chemotherapy and radiation. To limit this, researchers have tried to inhibit enzymes involved in the repair process. ‘There are multiple DNA repair pathways but there is no single enzyme that is common to all of them,’ said Dr. Marie Dutreix, CNRS research director at the Institut Curie. ‘As well as being effective, a therapeutic approach should also be non-toxic to healthy cells. With DT01, we have a unique approach.’
Instead of targeting a specific enzyme of a repair pathway, DT01 works upstream of all repair pathways by preventing the detection of damage caused by chemotherapy and/or radiation therapy. By disrupting the signaling of the damage sites, DT01 prevents repair and triggers the death of cancer cells as they divide. Worldwide, DNA Therapeutics is the only company working on disrupting the damage signal. The specific characteristics of cancer cells make them more vulnerable to the effects of DT01 than healthy cells, ensuring that the latter are not damaged by this novel therapy.
‘DT01 in combination with radiation therapy is safe and provides antitumor activity in patients with melanoma skin metastases,’ said Dr. Christophe Le Tourneau, head of early-phase clinical trials at the Institut Curie and principal investigator for this trial. ‘The DT01 systemic passage and the correlation between DT01 blood exposure and efficacy suggest a systemic effect. This trial opens the path for DT01 systemic administration in combination with chemo/radiotherapy.’
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