Traslational Cancer Drugs Pharma, S.L. has announced in BioSpain that their Phase I study performed in patients with advanced solid tumors with TCD-717 has been successfully completed. TCD-717 is a first-in-class, small molecule that precisely inhibits Choline Kinase Alpha, an enzyme heavily involved in the carcinogenic process. A total of 28 patients were enrolled in the trial, which was conducted in two leading medical centers in the U.S. in accordance with FDA approval.
“The completion of the first trial with TCD-717 represents a significant milestone for the Company. Our development team led by Dr. Beatriz Palacios has worked tirelessly to advance TCD-717 from the bench to the initiation of Phase II. With TCD-717 we are implementing a novel strategy of targeting phospholipid metabolism for the treatment of cancer. This first-in-class drug signals the adoption of a new treatment paradigm” said TCD’s President and Chairman of the Board, Pablo Cabello.
About the Trial
The trial was designed to primarily assess the safety and tolerability, pharmacokinetics and preliminary efficacy of TCD-717 given by intravenous infusion in patients with metastatic or recurrent advanced solid tumors refractory after standard therapy. Each patient was to receive 2 weekly administrations of TCD-717 for a total of six 4-week cycles, unless disease progression or dose limiting toxicity occurred. Patients were enrolled in ascending dose cohorts of 1-6 patients and were monitored for evidence of dose-limiting toxicity. Once the maximum tolerated dose (MTD) was reached, additional patients were enrolled to confirm this dose.
The objectives of the trial have been fully met. A total of 28 patients have entered the study (median age: 59 years; around 50% of each sex). The dose-escalation part of the study was completed very successfully with the identification of an MTD which provides systemic exposure to TCD-717 of at least 9x higher than the levels required to give efficacy preclinical in vivo models. This ensures that the MTD selected is clearly in the efficacious range. The safety/tolerability of this dose was clearly proven since no clinically significant adverse events or other abnormalities were reported.
Additionally, signs of activity have been observed, even though the clinical trial population used was very resistant to previous treatments (41% received ?5 prior chemotherapies; 75% never responded). Twenty-two percent of the patients completing at least one cycle at the MTD dose level presented a decrease of tumor size of 5-9% after 2 cycles of treatment. These patients had progressed either in all previous standard treatments or those administered during the last 4 years. Another 2 patients also presented stable disease after 2 cycles of treatment accompanied by complete elimination of ascitic fluid drainage or a marked decrease in tumoral markers compared to baseline.
More relevant trial information is available on ClinicalTrials.gov.
The Company is currently designing its Phase II program and is confident that TCD-717 will show clear efficacy without safety issues as first line treatment in patients overexpressing ChoK? in combination with standard of care treatment.
About Choline Kinase Alpha (ChoK?)
Choline Kinase Alpha (ChoK?) is a key enzyme regulating the production of phosphatidylcholine, a critical structural component required for the formation of the cell membrane and cell proliferation. Due to this role, ChoK? belongs to a very unique type of molecules that are essential for the carcinogenic process.
TCD has demonstrated that the up-regulation of ChoK? is a critical element for the acquisition of the tumor phenotype and that this enzyme participates in at least three of the major steps in the generation of cancer: independent cell proliferation; evasion of apoptosis (cell death); and increased cell motility and metastasis.
ChoK? overexpression is an indicator of the more aggressive nature of the tumor. Thus, the use of ChoK?-inhibitors is expected to be effective in all tumor types, including those which are more aggressive and harder-to-treat. Lung, breast, colorectal, ovarian, prostate and bladder cancers are just a few among the many cancer types characterized by ChoK? overexpression.
TCD-717 is a first-in-class, small molecule that precisely inhibits ChoK?. By inhibiting ChoK? TCD-717 targets destruction of the cancer cells with minimal effects on normal cells. The difference in response to ChoK? inhibition between cancer cells and normal cells derives from the addiction of tumor cells to phosphatidylcholine. While ChoK? inhibition causes a temporary and reversible arrest of proliferation in normal cells, the tumor cells attempt to overcome ChoK? inhibition by activation of an alternative mechanism to generate phosphatidylcholine. This alternative mechanism enables the cell, to some extent, to continue the phosphatidylcholine production process, however, it also leads to the production of ceramides, a lethal metabolite that promotes apoptosis (programmed cell death) and causes the specific destruction of the cancer cell. It is this different response to ChoK? inhibition between tumor cells and normal cells that makes TCD-717 a uniquely effective targeted treatment with an evident and overwhelming advantage over conventional, non-specific chemotherapy.
Article adapted by Medical News Today from original press release.