【醒目】Rociletinib （CO1686）一期临床结果（ASCO2013全文）

等翻译出来。

CO-1686这药不妙了。
Shares of Clovis (CLVS -10.9%) are down on higher volume after the company fumbled how it presented data on CO-1686 at ASCO. The BTD-designated EGFR inhibitor is being studied for the treatment of non-small cell lung cancer.
Positive buzz was generated by a presentation of interim Phase 2 data by a Harvard Medical School Professor that implies progression-free survival of 12 months.
The stumble occurred later during an off-site analyst meeting where the company disclosed that "three or four" patients had to initiate insulin therapy after becoming resistant to metformin. The way the firm chose to disclose a potential hyperglycaemia risk prompted some observers to question its transparency.
4名服用CO-1686的病人出现高血糖的副作用，使用二甲双胍降血糖，其中3名控制不住，转为使用胰岛素。

可惜了

看到马哥真是高兴!那4002服用时还是注意要观察血糖吧.

看到马哥就知道又有啥新东西了

CLOVIS ONCOLOGY RECEIVES BREAKTHROUGH THERAPY DESIGNATION FOR CO-1686 FOR THE TREATMENT OF SECOND-LINE EGFR MUTANT NON-SMALL CELL LUNG CANCER (NSCLC) IN PATIENTS WITH THE T790M MUTATION
BOULDER, Colo.--(BUSINESS WIRE)--May 19, 2014-- Clovis Oncology, Inc. (NASDAQ: CLVS) announced today that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation for the Company’s investigational agent CO-1686 as monotherapy for the treatment of second-line EGFR mutant NSCLC in patients with the T790M mutation. The Breakthrough Therapy designation was granted based on interim efficacy and safety results from an ongoing Phase 1/2 study of CO-1686. 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 in patients with initial activating EGFR mutations as well as the dominant resistance mutation T790M.

“We very much appreciate this designation by FDA, which recognizes the meaningful benefit CO-1686 may provide patients with T790M positive NSCLC,” said Patrick J. Mahaffy, President and CEO of Clovis Oncology. “This designation is well timed for us as well, as the increased interaction with FDA that it provides will come as we are initiating our registration studies and preparing to submit our initial New Drug Application (NDA) by mid-2015.”

Interim results from an ongoing Phase 1/2 study of CO-1686 were presented at the 4th European Lung Cancer Conference (ELCC) in Geneva in late March. An objective response rate of 64 percent in 14 of 22 evaluable T790M positive patients was observed. CO-1686 is well-tolerated, with only one patient who discontinued treatment with CO-1686 due to adverse events. There was no evidence of systemic wild-type EGFR inhibition.

The next update of CO-1686 clinical data will be presented at the 2014 American Society of Clinical Oncology Annual Meeting in a Clinical Science Symposium titled, “Targeting EGFR: The Next 10 Years”, taking place on Saturday, May 31 in Chicago.

The Company is currently enrolling two Phase 2 expansion cohorts of its Phase 1/2 study in EGFR mutant patients with the T790M mutation. Data from the expansion cohorts, combined with data from the TIGER2 study, in T790M positive patients directly after progression on their first and only TKI therapy, are expected to serve as the basis of an NDA submission for CO-1686 by mid-2015.

About Breakthrough Therapy Designation

The Breakthrough Therapy designation was enacted as part of the 2012 FDA Safety and Innovation Act and is intended to expedite development and review of drugs to treat serious or life-threatening medical conditions when preliminary clinical evidence demonstrates that the drug may have substantial improvement on at least one clinically significant endpoint over available therapies. Breakthrough Therapy designation includes all the features of the Fast Track designation, as well as more intensive guidance from the FDA on a drug’s clinical development program.

虽然难道露面，一露面就给大家带来新消息，谢谢了

老马，看了你最早的前沿信息，及时吃上了9291，使我家病情转危为安，好感谢你了，希望你又一次出现，再给我们带来光明，谢谢了。

An update of clinical data from the rociletinib Phase 1/2 study were presented in early June in an oral session at the American Society of Clinical Oncology (ASCO) Annual Meeting. Highlights from the data presented for evaluable, centrally-confirmed T790M positive patients treated at a therapeutic dose of rociletinib included a 58 percent objective response rate, and a 90 percent disease control rate. The median duration of response could not yet be determined, and similarly, median progression-free survival (PFS) had not yet been reached. However, follow-up for some patients exceeded one year and the estimate for median PFS was greater than 12 months. Rociletinib is well-tolerated, with no evidence of 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.

Rociletinib is the only EGFR-directed therapy to spare wild-type EGFR in clinical studies, which the Company believes represents a significant point of differentiation from approved EGFR inhibitors and those currently in clinical development.

The next update of CO-1686 clinical data is expected to take place at the 26th EORTC-AACR-NCI Symposium on Molecular Targets and Cancer Therapeutics in Barcelona in mid-November.

The Company 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 TIGER2 registration study patient population. 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. The TIGER2 study, in T790M positive patients directly after progression on their first and only TKI therapy, began enrolling patients earlier in the second quarter at a dose of 625mg BID.

Data from the expansion cohorts, combined with data from TIGER2, are expected to serve as the basis of an NDA submission for rociletinib by mid-2015.

In May, 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.

Clovis expects to initiate two more studies in the TIGER program during 2014. The TIGER1 study, a randomized Phase 2/3 registration study of rociletinib versus erlotinib in newly-diagnosed EGFR mutant patients is expected to begin shortly. The TIGER3 study, a randomized, comparative study of rociletinib versus chemotherapy in patients with EGFR-mutant NSCLC and acquired TKI resistance, is expected to begin during the second half of 2014. In addition, the Company initiated its Phase 1 study of rociletinib in Japan earlier this year.

Rociletinib

An update of clinical data from the rociletinib Phase 1/2 study were presented in early June in an oral session at the American Society of Clinical Oncology (ASCO) Annual Meeting. Highlights from the data presented for evaluable, centrally-confirmed T790M positive patients treated at a therapeutic dose of rociletinib included a 58 percent objective response rate, and a 90 percent disease control rate. The median duration of response could not yet be determined, and similarly, median progression-free survival (PFS) had not yet been reached. However, follow-up for some patients exceeded one year and the estimate for median PFS was greater than 12 months. Rociletinib is well-tolerated, with no evidence of 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.

Rociletinib is the only EGFR-directed therapy to spare wild-type EGFR in clinical studies, which the Company believes represents a significant point of differentiation from approved EGFR inhibitors and those currently in clinical development.

The next update of CO-1686 clinical data is expected to take place at the 26th EORTC-AACR-NCI Symposium on Molecular Targets and Cancer Therapeutics in Barcelona in mid-November.

The Company 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 TIGER2 registration study patient population. 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. The TIGER2 study, in T790M positive patients directly after progression on their first and only TKI therapy, began enrolling patients earlier in the second quarter at a dose of 625mg BID.

Data from the expansion cohorts, combined with data from TIGER2, are expected to serve as the basis of an NDA submission for rociletinib by mid-2015.

In May, 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.

Clovis expects to initiate two more studies in the TIGER program during 2014. The TIGER1 study, a randomized Phase 2/3 registration study of rociletinib versus erlotinib in newly-diagnosed EGFR mutant patients is expected to begin shortly. The TIGER3 study, a randomized, comparative study of rociletinib versus chemotherapy in patients with EGFR-mutant NSCLC and acquired TKI resistance, is expected to begin during the second half of 2014. In addition, the Company initiated its Phase 1 study of rociletinib in Japan earlier this year.