Clovis Oncology, Inc. (NASDAQ: CLVS) announced today that the TIGER2 study has commenced with the dosing of the first patient at a U.S. study site. CO-1686 is the Company's novel, oral, targeted covalent (irreversible) inhibitor of mutant forms of the epidermal growth factor receptor (EGFR) for the treatment of non-small cell lung cancer (NSCLC) in patients with initial activating EGFR mutations as well as the dominant resistance mutation T790M.
"In the clinic, we are seeing an increasingly acute need for effective treatments against T790M," said Lecia V. Sequist, MD, MPH, Massachusetts General Hospital Cancer Center and Associate Professor of Medicine at Harvard Medical School and the lead investigator for the Phase 1/2 study of CO-1686. "CO-1686 provides an avenue of hope for these patients who otherwise may have to resort to the old standard of chemotherapy treatment which is often ineffective and comes with many more side effects."
"We are pleased to begin enrolling TIGER2, our registration study for CO-1686 focused on T790M positive patients who have progressed following their first EGFR-targeted therapy," said Patrick J. Mahaffy, President and CEO of Clovis Oncology. "The CO-1686 data observed to date have been highly consistent, including the growing evidence of a lengthy duration of benefit and the tolerability profile of the drug. We remain committed to filing an NDA by mid-2015 based on this study and the ongoing TIGERX expansion cohorts."
Data recently presented at the 2014 American Society of Clinical Oncology annual meeting included activity and safety results in 40 evaluable centrally-confirmed T790M positive patients across efficacious dose levels in the Phase 1 dose-expansion study and the early Phase 2 expansion cohorts. These include 23 partial responses (PRs) observed as of early May, for a 58 percent objective response rate (ORR). Thirty-six of the 40 evaluable T790M positive patients, or 90 percent, have experienced stable disease or a PR. Central nervous system (CNS) responses have also been observed in heavily pre-treated T790M positive patients. The median duration of response cannot yet be determined in the T790M positive patients. Similarly, median PFS has not been reached. However, follow-up for some patients exceeds one year, and the current estimate for median PFS is greater than 12 months. CO-1686 is well-tolerated, with no evidence of systemic wild-type EGFR inhibition. In the Phase 1 study, the most common adverse events were nausea, hyperglycemia, diarrhea, vomiting and decreased appetite, and these were mostly grade 1 or 2 in severity. The most common grade 3 adverse event was hyperglycemia, which was observed in 22 percent of patients. Hyperglycemia, when observed and requiring treatment, is typically managed with a commonly-prescribed single oral agent.
Breakthrough therapy designation was granted by the FDA last month for CO-1686 as monotherapy for the treatment of mutant EGFR NSCLC in patients with the T790M mutation after progression on EGFR-directed therapy.
The TIGER2 study is the first of three registration studies in the TIGER (Third-generation inhibitor of mutant EGFR in lung cancer) program expected to initiate during 2014. The TIGER2 study is being conducted in T790M positive patients directly after progression on their first and only TKI therapy. Study sites are now enrolling in the U.S., Europe and Australia. For more information about the study, please visit www.tigertrials.com.
The TIGER2 study is currently enrolling 125 patients with EGFR-mutant NSCLC with a centrally-confirmed T790M mutation who will receive CO-1686 at the recommended Phase 2 dose (RP2D) of 625mg BID. The primary study endpoint is overall response rate; secondary endpoints include duration of response, progression-free survival, overall survival, and safety.
In addition to TIGER2, Clovis is currently enrolling two Phase 2 expansion cohorts of its Phase 1/2 study in EGFR mutant patients with the T790M mutation; the first includes approximately 150 to 200 T790M positive patients directly after progression on their first and only TKI therapy, comparable to the population in its TIGER2 registration study. The second cohort includes approximately 150 to 200 later-line T790M positive patients after progression on their second or later TKI therapy or subsequent chemotherapy. Both cohorts are exploring doses of 500mg, 625mg and 750mg BID.
Data from the expansion cohorts, combined with data from TIGER2, are expected to serve as the basis of an NDA submission for CO-1686 by mid-2015.
Clovis expects to initiate the Phase 2 portion of the TIGER1 study, a randomized Phase 2/3 registration study of CO-1686 vs. erlotinib in newly-diagnosed EGFR mutant patients, in mid-2014. The TIGER3 study, a randomized, comparative study versus chemotherapy in T790M positive patients directly after progression on their first and only TKI therapy, is expected to initiate during the second half of 2014.
The Company initiated its Phase 1 study of CO-1686 in Japan during the first quarter of 2014.