Interim Data from Rociletinib (CO-1686) Phase 1/2 Study Shows Compelling and Durable Clinical Activity and Progression-free Survival (PFS) in Patients with EGFR-Mutant Non-small Cell Lung Cancer (NSCLC)

67% objective response rate (ORR) observed in evaluable heavily-pretreated T790M+ patients treated with 625mg or 500mg BID (clinical dose group)
Median PFS of 10.4 months in clinical dose group; data continue to mature
Well-tolerated – majority of treatment-related adverse events are grade 1-2
In T790M-negative patients treated with 625mg or 500mg BID, 36% ORR and median PFS of 7.5 months observed
Only TKI shown to spare wild-type EGFR signaling
U.S. and E.U. regulatory submissions planned in mid-2015
November 18, 2014 06:36 PM Eastern Standard Time
BARCELONA, Spain--(BUSINESS WIRE)--Clovis Oncology (NASDAQ:CLVS) announced today updated findings from its ongoing Phase 2 clinical study of rociletinib (CO-1686), the Company's novel, oral, targeted covalent (irreversible) mutant-selective inhibitor of the epidermal growth factor receptor (EGFR) for the treatment of NSCLC in patients with initial activating EGFR mutations as well as the primary resistance mutation T790M. These data are being presented Friday, November 21 in an oral presentation (Abstract No. LBA 10) by Professor Jean-Charles Soria at the 26th EORTC-NCI-AACR (ENA) Symposium on Molecular Targets and Cancer Therapeutics in Barcelona, Spain.

"These data demonstrate the very encouraging activity and tolerability observed with rociletinib at our go-forward dose of 625mg BID, and our step-down dose of 500mg BID"

"I have been involved in the clinical development of rociletinib since the first patient was dosed, and it is gratifying to see the progress made and the data presented at the ENA Symposium today," said Dr. Jonathan Goldman, Assistant Professor, UCLA Hematology & Oncology, Associate Director of Drug Development and Director of Clinical Trials in Thoracic Oncology. "In particular, the data presented are consistent with my own experience that the 625mg BID dose provides very encouraging efficacy with excellent tolerability. In addition, the early evidence of activity in the T790M negative patients is surprising and may address a remaining unmet medical need for this additional group of patients who have also progressed on initial TKI therapy."

"These data demonstrate the very encouraging activity and tolerability observed with rociletinib at our go-forward dose of 625mg BID, and our step-down dose of 500mg BID," said Patrick J. Mahaffy, President and CEO of Clovis Oncology. "We are now expanding beyond our initial focus on T790M-positive patients and are very enthusiastic about our expansion into front-line patients with TIGER-1, and soon, into an all-comer population of patients with acquired TKI resistance, including both T790M-positive and T790M-negative patients with TIGER-3. We are actively preparing for the first of our planned regulatory filings, which include the U.S. NDA and E.U. MAA in mid-2015."

Two Phase 2 expansion cohorts (known as TIGER-X) are currently enrolling in the United States, Europe, and Australia in EGFR mutant patients with the T790M mutation. Patients in these cohorts are receiving 625mg BID of the intended commercial tablet formulation of rociletinib, and data from these cohorts will form part of the NDA/MAA submission packages. The two cohorts include patients with T790M+ disease either after progression on their first and only TKI therapy, or after progression on their second or later TKI therapy or chemotherapy.

Data from 56 T790M-positive patients treated with rociletinib in the clinical dose group – which includes the recommended Phase 2 dose of 625mg BID (n=30) and the step-down dose of 500mg BID (n=26) – are being presented today, together with data from 11 T790M-negative patients treated at the same doses.

Patients in the clinical dose group were heavily pre-treated prior to receiving rociletinib; 79 percent of patients had immediately progressed on TKI therapy prior to rociletinib treatment. The median number of previous lines of therapy across patients was three.

Evidence of Activity

The objective response rate (ORR) in 27 evaluable T790M-positive patients receiving either 625 or 500mg BID was 67%. The ORR was comparable in the 625mg BID and 500mg BID dose groups. The disease control rate was 89% for the clinical dose group, and again, was consistent across doses. The median PFS for the clinical dose group was 10.4 months, with follow-up for some patients exceeding one year.

In 11 evaluable T790M-negative patients treated at 625 or 500mg BID, a 36% ORR and median PFS of 7.5 months were observed. This activity in the non-target T790M-negative patient group is surprising and may, in part, relate to the inhibition of IGF1-R (insulin growth factor receptor 1) by a metabolite of rociletinib. In addition to Clovis' other clinical trials focused on newly-diagnosed EGFR-mutant NSCLC patients in TIGER-1 and T790M-positive patients in TIGER-X and TIGER-2, the Company is now exploring treatment of the T790M-negative population in its TIGER-3 comparative study versus chemotherapy, which includes both T790M-positive and –negative patients. Forty percent of patients who progress on TKI therapy do so for reasons other than the T790M mutation, and this represents a serious unmet medical need.

Safety and Tolerability

Data presented at ENA demonstrate that rociletinib is well-tolerated, with no evidence of systemic wild-type EGFR inhibition. The most common treatment-related adverse events (AEs) reported in ≥15 percent of all patients included: hyperglycemia, diarrhea, nausea, and reduced appetite. Most adverse events were grade 1 or 2 in severity. The only grade 3/4 treatment-related adverse event observed in more than one patient was hyperglycemia (14 percent). Hyperglycemia, when observed and requiring treatment, is typically managed with a commonly-prescribed single oral agent.

CO-1686 Clinical Development

Clovis is currently enrolling several studies in EGFR-mutant NSCLC in addition to the TIGER-X expansion cohorts noted above:

The TIGER-2 study is currently enrolling patients with EGFR-mutant NSCLC with a centrally-confirmed T790M mutation directly after progression on their first and only TKI therapy. Patients receive rociletinib 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. This global study includes, for the first time, patients from Asian countries including South Korea, Taiwan and Hong Kong.
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 immediately follow. 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.
The TIGER-3 study is an international, randomized, comparative study of rociletinib versus chemotherapy in T790M-positive and T790M-negative patients with EGFR-mutant NSCLC and acquired TKI resistance, which is expected to initiate in the next few months. As well as measuring efficacy in T790M-positive patients, this study will explore whether rociletinib activity in all-comers, including T790M-negative patients, is superior to single-agent chemotherapy, the current standard of care.
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In addition, a Phase 1 study of rociletinib is underway in Japan and an expansion cohort is currently enrolling at 625mg BID to confirm a global recommended Phase 2 dose (RP2D).
Data from the TIGER-X expansion cohorts, combined with data from TIGER-2, are expected to serve as the basis of a U.S. NDA and E.U. MAA for rociletinib in mid-2015.

Presentation Details

The presentation, titled "Interim phase 2 results with the irreversible, mutant selective, EGFR inhibitor rociletinib (CO-1686)" is being presented on Friday, November 21, during Plenary Session 8, from 11:00 to 13:00 CET.

Event Webcast Details

Clovis will host an investor/analyst webcast conference call following the rociletinib data presentation at ENA Friday, November 21 from 14:00 to 15:00 CET. Dial in information for the U.S. is 877 280 4960 and International is 857 244 7317. The passcode is 78436017. The event will be simultaneously webcast on the Company's web site at, and archived for future review.

About Rociletinib

Rociletinib is an oral, potent, mutant-selective inhibitor of epidermal growth factor receptor (EGFR) under investigation for the treatment of EGFR mutated non-small cell lung cancer (NSCLC). Rociletinib targets the activating mutations to EGFR (L858R and Del19), while also inhibiting the primary resistance mutation, T790M, which develops in 60 percent of patients treated with first- and second-generation EGFR inhibitors.

As reported at ASCO earlier this year, rociletinib has demonstrated compelling efficacy in a heavily pre-treated, Western population of patients with acquired resistance to currently available EGFR inhibitors. In clinical trials to date, rociletinib is well-tolerated, without evidence of systemic wild-type EGFR inhibition. 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. Inhibition of wild-type EGFR is associated with cutaneous (and other) toxicities such as acneiform rash, stomatitis and paronychia, all of which may significantly impact patients' quality of life and result in treatment discontinuation and patient distress. Clovis believes the lack of wild-type EGFR inhibition in rociletinib's clinical profile represents a significant point of differentiation from approved EGFR inhibitors and those currently in clinical development. In May of 2014, the U.S. FDA granted Breakthrough Therapy designation for rociletinib as treatment for mutant NSCLC in patients with the T790M mutation after progression on EGFR-directed therapy.

About EGFR and Lung Cancer

Lung cancer is the most common cancer worldwide with 1.7 million new cases annually, with NSCLC accounting for almost 85 percent of all lung cancers. NSCLC progresses rapidly with a five-year survival rate in advanced NSCLC patients of less than five percent. EGFR activating mutations occur in approximately 10 to 15 percent of NSCLC cases in Caucasian patients and approximately 30 to 35 percent in Asian patients. These patients experience significant tumor response currently approved EGFR inhibitors which are first-generation EGFR inhibitors. However, most patients ultimately progress on these therapies, with approximately 60 percent of patients developing acquired resistance from a second, or "gatekeeper" mutation, T790M.

About Clovis Oncology

Clovis Oncology, Inc. is a biopharmaceutical company focused on acquiring, developing and commercializing innovative anti-cancer agents in the U.S., Europe and additional international markets. Clovis Oncology targets development programs at specific subsets of cancer populations, and simultaneously develops diagnostic tools that direct a compound in development to the population that is most likely to benefit from its use. Clovis Oncology is headquartered in Boulder, Colorado.

To the extent that statements contained in this press release are not descriptions of historical facts regarding Clovis Oncology, they are forward-looking statements reflecting the current beliefs and expectations of management made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements involve substantial risks and uncertainties that could cause our clinical development programs, future results, performance or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the uncertainties inherent in our clinical development programs for our drug candidates, the corresponding development pathways of our companion diagnostics, actions by the FDA, the EMA or other regulatory authorities regarding whether to approve drug applications that may be filed, as well as their decisions regarding drug labeling, and other matters that could affect the availability or commercial potential of our drug candidates or companion diagnostics, including competitive developments. Clovis Oncology does not undertake to update or revise any forward-looking statements. A further description of risks and uncertainties can be found in Clovis Oncology's filings with the Securities and Exchange Commission, including its Annual Report on Form 10-K and its reports on Form 10-Q and Form 8-K.

Clovis Oncology
Anna Sussman, 303-907-5358
[email protected]
Breanna Burkart, 303-907-5162
[email protected]