The incidence of adverse events did not increase with dose escalation and does not appear to be dose dependent. These data offer no evidence of dose-related adverse events related to wild-type EGFR inhibition by CO-1686.
In August, the Company transitioned development of CO-1686 from an initial free base capsule presentation to a tablet HBr formulation. Preliminary pharmacokinetic data from the first cohort of three patients treated at 500mg BID are being presented today. The HBr formulation at the 500mg BID dose was expected to demonstrate approximately equivalent exposures with reduced variability compared with the free base formulation at the 900mg BID dose. Data from the first cohort of the HBr formulation has demonstrated far greater exposures than expected, with no adverse events. There has been no evidence of cutaneous or gastrointestinal toxicity of any grade in the 500mg BID cohort, and no dose limiting toxicity, and enrollment of the 750mg BID cohort has commenced.
The presentation, titled “First-in-human evaluation of CO-1686, an Irreversible, Selective, and Potent Tyrosine Kinase Inhibitor of EGFR T790M (Activating and T790M),” is being presented on Monday, October 28, between 10:30am-12 noon in the Bayside B Auditorium at the Sydney Convention and Exhibition Centre. The presentation will also be available at
CO-1686 is a novel, oral, targeted covalent (irreversible) inhibitor of the cancer-causing mutant forms of epidermal growth factor receptor (EGFR) currently being studied for the treatment of non-small cell lung cancer (NSCLC). CO-1686 was designed to selectively target both the initial activating EGFR mutations as well as the T790M resistance mutation, while sparing wild-type, or “normal” EGFR at anticipated therapeutic doses. Accordingly, it has the potential to treat NSCLC patients with EGFR mutations both as a first-line or second-line treatment with a reduced toxicity profile compared to current EGFR inhibitor therapies. The Phase I/II study is currently in the dose escalation phase, being conducted in the U.S., France and Australia. Following the establishment of an appropriate dose, the Company intends to study CO-1686 in Phase II expansion cohorts of NSCLC patients with activating EGFR mutations who have failed initial EGFR-directed therapy and have developed the T790M resistance mutation as well as NSCLC treatment-naïve patients with activating EGFR mutations.