Originally published June 23.
NEW YORK (GenomeWeb) – Clovis Oncology has launched the TIGER2 study for its non-small cell lung cancer drug CO-1686, an agent the company is studying as a treatment for advanced patients with tumors characterized by EGFR mutations and the T790M resistance mutation.
CO-1686 is an irreversible EGFR inhibitor. Clovis this week said it has dosed the first patient in the TIGER2 Phase I/II trial, which is focused on gauging the efficacy of CO-1686 in NSCLC patients who have progressed on their first and only anti-EGFR treatment.
Clovis has said it intends to file an NDA for CO-1686 by mid-2015 based on the results of TIGER2 and ongoing TIGERX expansion cohorts.
TIGER2 is one of three registration trials in Clovis' TIGER, or third-generation inhibitor of mutant EGFR in lung cancer, program for CO-1686. TIGER2 will enroll 125 T790M-positive NSCLC patients right after they have disease progression following their first tyrosine kinase inhibitor. The patients will receive CO-1686 at the recommended Phase II dose of 625 mg twice a day. The primary study objective is to gauge the impact of the drug on patients' overall response rate. Researchers will also look at other endpoints, including duration of response, progression-free survival, overall survival, and safety.
At the American Society of Clinical Oncology's annual meeting earlier this month, researchers from Clovis and elsewhere presented data on 40 evaluable patients with T790M mutations receiving various doses of CO-1686. In that analysis, 23 patients had partial responses and 36 out of 40 patients had either a partial response or stable disease. Some heavily pretreated patients with T790M mutations also had central nervous system responses.
Median duration response and progression-free survival have not been reached in this study. However, with some patients having follow-up for more than one year, researchers estimate that progression-free survival will likely exceed 12 months in this study. Most toxicities in patients were mild, although Grade 3 hyperglycemia was seen in 22 percent of patients.
The aim of next-generation EGFR inhibitors for advanced NSCLC is to battle resistance to first-generation drugs and more accurately target mutant tumor cells. At the ASCO meeting, CO-1686 was among a handful of new anti-EGFR agents that sponsors presented early data on. In this regard, CO-1686 was specifically designed to have reduced binding affinities for EGFR proteins without one of the resistance mutations, and has been shown in studies to spare wild-type EGFR cells.
Similar to TIGER2, Clovis is conducting a second study of up to 200 T790M-positive NSCLC patients after they've progressed on their first tyrosine kinase inhibitor. In a third study, Clovis is studying 200 patients with T790M-positive tumors who have progressed on later lines of tyrosine kinase inhibitors or chemotherapy. In these studies, patients will receive 500 mg, 625 mg, or 750 mg twice a day.
The company will soon initiate the Phase II part of the TIGER1 Phase II/III randomized registration trial, comparing CO-1686 versus Tarceva (erlotinib) in newly diagnosed NSCLC patients with EGFR mutant tumors. Then in the last half of this year, Clovis will start TIGER3, a randomized trial comparing CO-1686 against chemotherapy in T790M positive NSCLC patients who have progressed on their first tyrosine kinase inhibiting drug. Earlier this year, the company began studying the drug in Japan.