The Phase I dose escalation portion of the study is being conducted in the United States, France and Australia in patients with metastatic or unresectable recurrent NSCLC and a documented EGFR mutation. Patients were not required to be T790M positive for the Phase I portion of the study but had to have progressed on prior EGFR-directed tyrosine kinase inhibitor (TKI) therapy (prior chemotherapy was also allowed).
Evidence of Activity
As of October 2013, nineteen patients have been treated in the 900mg BID cohort. Of those nineteen patients, five were T790M negative and fourteen were T790M positive (five non-evaluable).
In the nine evaluable T790M positive patients, a 67 percent overall response rate was demonstrated. Six patients achieved RECIST partial responses and two patients achieved tumor shrinkage of 10-20 percent. Patients were heavily pretreated prior to receiving CO-1686; eight of the nine patients had immediately progressed on a TKI prior to treatment. Six of the nine patients received two or more previous TKI lines. As expected, no objective responses were seen in T790M negative patients.
Previously, the Company reported data at ASCO for a total of four evaluable T790M positive patients treated in the 900mg BID cohort; one patient with stable disease and three patients with PRs. Additionally, the Company reported one patient with a PR from the 300mg BID cohort. Of the four patients with PRs, three of the four remain on drug. Two patients have maintained their responses and one patient remains on drug despite having formally progressed. The median progression free survival time for these four responding patients has not yet been reached but is greater than 181 days.
Safety and Tolerability
CO-1686 appears to be well-tolerated with no evidence of rash or dose-related diarrhea. There are limited and low-grade adverse events in patients to date. The most common adverse events attributed to CO-1686 therapy include nausea (21%), diarrhea (20%), fatigue (20%), vomiting (13%) and decreased appetite (11%). These did not lead to study drug discontinuation.