Clovis Oncology enrolls first patient in TIGER-1 study

Rociletinib is the Company’s novel, oral, targeted covalent (irreversible) mutant-selective inhibitor 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 primary resistance mutation T790M.

"I am pleased to lead the US trial of first-line rociletinib in patients with EGFR-mutant NSCLC," said Ross Camidge, MD, PhD, Associate Professor, Division of Medical Oncology, University of Colorado School of Medicine and the lead investigator for the TIGER-1 study in the United States.

"The rociletinib clinical data observed to date in the second-line EGFR-mutant population after failure of drugs like erlotinib have been highly encouraging and consistent, really making the case to try this drug in these patients from the outset. The absence of side effects associated with wild-type EGFR inhibition from this drug is also likely to be welcomed by patients."

"It is exciting that less than five years after the initial TKI was confirmed as standard first-line treatment for EGFR-mutant NSCLC, we are ready to begin the first randomized study proving the role of a third-generation EGFR inhibitor in this population," said Tony Mok, Professor of Clinical Oncology, the Chinese University of Hong Kong, and the lead investigator for the TIGER-1 study in Asia.

"Rociletinib is a very promising compound which targets both the activating mutations and the resistant exon 20 T790M mutation. It is our objective to prove a higher efficacy with rociletinib in the TIGER-1 study. With the high incidence of EGFR mutations in this region, I trust TIGER-1 will roar in Asia."

"Patients with EGFR-mutant lung cancer are hungry for a new treatment option that can extend progression-free survival beyond what is seen with the first-generation EGFR inhibitors available today, particularly an option without the rash that make current treatments difficult for many patients," said Bonnie J. Addario, founder of The Bonnie J. Addario Lung Cancer Foundation, one of the largest philanthropies (patient-founded, patient-focused, and patient-driven) devoted exclusively to eradicating Lung Cancer through research, early detection, education, and treatment.

"The evident activity and clear lack of rash and other side effects associated with wild-type EGFR inhibition makes us very enthusiastic about the potential for this drug and this study. I believe the development of targeted therapies like rociletinib represents one of the most important scientific advances of this decade."

In pre-clinical testing, rociletinib demonstrated significant reductions in tumor volume in subcutaneous xenograft and genetically-engineered mouse models with each of the two activating mutations (exon 19 deletion, L858R mutation), collectively observed in approximately 85 percent of EGFR-mutant NSCLC patients.

Consistent with rociletinib sparing wild-type EGFR, there was no reduction in body weight in the animals treated with rociletinib whereas body weight loss was observed in the animals treated with erlotinib or afatinib.

In approximately 60 percent of patients with EGFR-mutant NSCLC, acquired resistance to current EGFR TKIs is driven by a secondary T790M mutation in EGFR. In a front-line PC-9 (EGFRDel19) model rociletinib and erlotinib were compared over time to determine when resistance emerged. Resistant tumors emerged around day 30 in erlotinib-treated mice whereas no tumor regrowth was observed in mice treated up to 86 days with rociletinib.

The TIGER-1 study is the second of three registration studies in the program expected to initiate during 2014. The TIGER-1 study is a randomized Phase 2/3 registration study of rociletinib vs. erlotinib in newly-diagnosed EGFR-mutant patients. The Phase 2 portion of the study will enroll 200 patients.

Upon completion of enrollment of the Phase 2 portion of the study, the Phase 3 portion of the study will initiate. The Phase 3 portion is a blinded study and the sizing will be determined in part by the initial data from the Phase 2 portion of the study. Study sites are currently enrolling in the U.S. and will enroll soon in Europe, Australia and Asia.