TRACON Pharmaceuticals Inc (NASDAQ:TCON), which develops a clinical-stage pipeline of cancer therapies, announced the publication in the Cancer Cell journal of clinical data that provides molecular insight into its drug TRC102’s mechanism of action and the patient populations most likely to respond to treatment.
The article, entitled, “Molecular Features of Cancers Exhibiting Exceptional Responses to Treatment,” highlighted the clinical features and tumor biology of an exceptional responder patient treated with TRC102 at the National Cancer Institute (NCI).
The San Diego, California-based company said the patient was diagnosed with metastatic and highly refractory colorectal cancer and received temozolomide (Temodar) and TRC102. Following treatment, the patient was considered an “exceptional responder” through the achievement of a near complete response lasting “45 months at the most recent follow-up.”
TRACON said detailed molecular analyses of the patient’s tumor showed “silencing of DNA repair pathways that may have resulted in sensitivity to the inhibition of DNA base excision repair pathway by TRC102.” The authors hypothesized that the Temodar and TRC102 combo was effective because all necessary DNA repair pathways were “compromised genetically or through the activity of TRC102.”
“O6-Methylguanine-DNA-methyltransferase (MGMT) expression was also assessed in biopsies from 11 colorectal patients who subsequently enrolled in an expansion cohort, one of which demonstrated a partial response,” said the company. The tumor linked to the partial response did nog express MGMT, whereas each of the 10 tumors that did not respond to therapy expressed this enzyme robustly.
TRC102 is being studied in multiple Phase 1 and Phase 2 clinical trials sponsored by the NCI through a Cooperative Research and Development Agreement (CRADA). TRC102 was evaluated in a Phase 2 trial in combination with Temodar chemotherapy in 19 patients with progressive or recurrent glioblastoma, who progressed following Temodar and external beam radiotherapy.
Extended survival was observed in two patients for more than two years, both of whom demonstrated activation of the DNA base excision repair pathway and showed hyperactivation of DNA damage response genes prior to treatment with TRC102, said the company.
“The Cancer Cell publication supports our belief that patients whose cancers are dependent on the DNA base excision repair pathway to repair DNA damage from chemotherapy may be particularly sensitive to the pharmacologic effects of TRC102,” said TRACON chief Medical Officer James Freddo.
“The NCI data are also consistent with the results from the Phase 2 trial of Temodar and TRC102 in refractory glioblastoma. We remain committed to developing TRC102 in collaboration with the NCI and believe that the data generated to date provide strong rationale for studying TRC102 in combination with Temodar and radiotherapy in newly diagnosed patients with malignant glioma.”
In October this year, TRC102 was granted orphan drug designation by the US Food and Drug Administration for the treatment of malignant glioma, including glioblastoma, an aggressive type of cancer that can occur in the brain or spinal cord.
With orphan designation, TRACON qualifies for various incentives with respect to TRC102 for the treatment of glioblastoma, including tax credits for qualified clinical trials.
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