Publication of two pivotal Phase III studies of regorafenib: Positive Phase III Data on Bayer's Regorafenib in Metastatic

Publication of two pivotal Phase III studies of regorafenib: Positive Phase 
III Data on Bayer's Regorafenib in Metastatic Colorectal Cancer (mCRC) and 
Gastrointestinal Stromal Tumor (GIST) Published in The Lancet 
--  First publication of the global Phase III CORRECT and GRID 
    study data of the oral multi-kinase inhibitor regorafenib 
TORONTO, Nov. 27, 2012 /CNW/ - Bayer HealthCare today announced that the 
results of two pivotal Phase III studies for regorafenib were published online 
in the journal The Lancet ahead of a future print publication. Data from the 
CORRECT (Metastatic Colorectal cancer treated with regorafenib or placebo 
after failure of standard therapy) and GRID (GIST - Regorafenib In Progressive 
Disease) trials provide robust evidence for the efficacy of regorafenib in 
patients with metastatic colorectal cancer (mCRC) or gastrointestinal stromal 
tumor (GIST) who have exhausted all other treatment options. 
"The publication of the CORRECT and GRID trials in The Lancet signifies the 
potential of regorafenib as a new and effective treatment option for both mCRC 
and GIST, where there is a high unmet need," said Dr. Shurjeel Choudhri, Vice 
President, Medical and Scientific Affairs. "Bayer is dedicated to developing 
innovative therapies to improve patient's lives and we will continue to expand 
our oncology portfolio to make a difference for patients and physicians." 
In the Phase III CORRECT trial regorafenib plus best supportive care (BSC) 
significantly improved overall survival (OS) (HR=0.77, 1-sided p-value=0.0052) 
and progression-free survival (PFS) (HR=0.49, 1-sided p-value <0.000001) 
compared to placebo plus BSC in patients with mCRC whose disease had 
progressed after approved standard therapies. In the study, median OS was 6.4 
months with regorafenib versus 5.0 months with placebo; median PFS was 1.9 
months with regorafenib versus 1.7 months with placebo. The data also showed a 
survival benefit in the regorafenib arm across nearly all subgroups analyzed, 
including no significant difference between patients with KRAS wild-type tumor 
and those with KRAS mutant tumor. No difference in overall response rate was 
"Although there has been progress in the treatment of metastatic colorectal 
cancer, drug resistance remains a huge challenge," says Dr. Christine Cripps, 
Professor of Medicine University of Ottawa Cancer Centre. "Regorafenib is a 
unique oral multi-kinase inhibitor that has the potential to become a new 
standard of care in mCRC and provides hope for those patients who until now 
would have had no further options." 
The most common grade 3+ adverse events (≥5% of patients) were hand-foot 
skin reaction (16.6% vs. 0.4%), fatigue (15.0% vs. 8.3%), diarrhea (8.2% vs. 
2.0%), hypertension (7.6% vs. 0.8%), and rash/desquamation (5.8% vs 0.4%). 
Quality of life was not adversely affected by regorafenib. The most serious 
adverse drug reactions in patients receiving regorafenib were severe liver 
injury, hemorrhage and gastrointestinal perforation. 
GRID Trial 
The Phase III GRID trial, also published in The Lancet, showed that 
regorafenib plus BSC significantly improved PFS compared to placebo plus BSC 
(HR=0.27, p<0.000001) in patients with metastatic and/or unresectable GIST who 
were previously treated with imatinib and sunitinib, which means a 73% 
reduction in the risk of progression or death. The median PFS was 4.8 months 
in the regorafenib arm versus 0.9 months in the placebo arm. In addition, 
there was a positive trend in the regorafenib group in improving OS (HR=0.772, 
p=0.199); however, the OS did not reach statistical significance which was 
expected due to the cross-over design of the trial that allowed patients 
receiving placebo to receive regorafenib following disease progression. 
Furthermore, a significantly greater disease control rate (DCR) was observed 
with regorafenib plus BSC compared to placebo plus BSC (52.6% vs. 9.1%; 
p<0.000001), DCR was defined as rate of complete response [CR] plus partial 
response [PR] plus durable stable disease [SD] maintained for at least 12 
weeks. In addition, regorafenib demonstrated therapeutic benefit independent 
of prior treatment options based on analysis in pre specified subgroups that 
showed regorafenib had a statistically significant PFS benefit over placebo 
for patients receiving regorafenib as a third- or fourth-line treatment. 
The most common grade 3 regorafenib-related adverse events which had higher 
incidence (≥5% ) in the regorafenib plus BSC vs placebo plus BSC were 
hypertension (27.3% vs 4.5%), hand-foot skin reaction (20.5% vs 0%), and 
diarrhea (7.6% vs 0%%). Grade 4 AEs were reported at a similar incidence in 
the regorafenib plus BSC vs placebo plus BSC (6.8% vs 6.1%). 
About the CORRECT Trial 
The Phase III study CORRECT randomized 760 patients with mCRC whose disease 
had progressed after currently approved standard therapies to receive 
regorafenib plus BSC or placebo plus BSC at a 2:1 ratio. Treatment cycles 
consisted of 160 mg of regorafenib (or matching placebo) once daily for three 
weeks on / one week off plus BSC. The primary endpoint of this trial was OS. 
Secondary endpoints included PFS, objective tumor response rate and disease 
control rate. The safety and tolerability of the two treatment groups were 
also compared. 
About the GRID Trial 
GRID was a randomized, double-blind, placebo-controlled, multi-center, 
cross-over Phase III study of regorafenib for the treatment of GIST. It 
randomized 199 patients whose disease had progressed despite prior treatment 
with imatinib and sunitinib. Patients were randomized in a 2:1 ratio to 
receive either regorafenib (160 mg once daily, 3 weeks on/1 week off) plus BSC 
or placebo plus BSC to evaluate efficacy and safety. The primary endpoint of 
this trial was PFS, and secondary endpoints included OS, time to progression, 
disease control rate, tumor response rate, duration of response, and safety of 
regorafenib. Patients initially randomized to placebo were allowed to cross 
over to open-label regorafenib once the disease progressed, of which 85% of 
the patients from the placebo arm did cross over. 
About Stivarga(®) (regorafenib) 
Regorafenib is an oral multi-kinase inhibitor that inhibits various kinases 
that are involved in mechanisms associated with tumor growth and progression 
(oncogenesis), blood vessel development (angiogenesis), and the tumor 
microenvironment. In preclinical studies, Stivarga inhibits several angiogenic 
VEGF receptor tyrosine kinases (VEGFR1 and murine VEGFR2/3) that play a role 
in tumor neoangiogenesis (the growth of new blood vessels). It also inhibits 
various oncogenic and tumor microenvironment kinases including, KIT, RET, 
RAF-1, B-RAF, B-RAF(V600E), PDGFR, and FGFR1, which individually and 
collectively impact upon tumor growth, formation of a stromal microenvironment 
and disease progression. 
Regorafenib has been submitted to Health Canada for marketing approval for the 
treatment of metastatic CRC and GIST. Market authorization in Canada has not 
yet been obtained. 
Regorafenib was approved by the U.S. Food and Drug Administration for the 
treatment of mCRC and is marketed as STIVARGA(®) and has received priority 
review for treatment in GIST. Bayer has also submitted for marketing 
approval of regorafenib for the treatment of metastatic CRC in the EU in May 
2012. The NDA for regorafenib for the treatment of advanced CRC filed in Japan 
in July 2012 was granted priority review. 
Stivarga is a Bayer compound developed by Bayer and jointly promoted by Bayer 
and Onyx in the U.S. In 2011, Bayer entered into an agreement with Onyx, under 
which Onyx receives a royalty on all future global net sales of Stivarga in 
About Bayer Inc. 
Bayer Inc. (Bayer) is a Canadian subsidiary of BayerAG, an international 
research-based group with core businesses in health care,crop science and 
innovative materials. Headquartered inToronto, Ontario, BayerInc. operates 
the Bayer Group's HealthCare and MaterialScience businesses inCanada.Bayer 
CropScience Inc.,headquartered in Calgary, Alberta operates as aseparate 
legal entity inCanada. Together, the companies play a vital role in 
improving the quality oflife for Canadians - producing products that fight 
diseases, protecting cropsand animals, anddeveloping high-performance 
materials for applications innumerous areas of daily life.CanadianBayer 
facilities include the Toronto headquarters and offices in Montréal 
Bayer Inc. has approximately800 employees across Canada and had sales of 
$808 million CDN in 2011.Globally, the Bayer Group had sales of over 36 
billion Euro in 2011. Bayer Inc.investedapproximately $13 million CDN in 
research and development in 2011.Worldwide, the Bayer Group spent the 
equivalent of over 2.9 billion Euro in2011 in R&D. For more information, go 
Forward-Looking Statements 
This release may contain forward-looking statements based on current 
assumptions and forecasts made by Bayer Group or subgroup management. Various 
known and unknown risks, uncertainties and other factors could lead to 
material differences between the actual future results, financial situation, 
development or performance of the company and the estimates given here. These 
factors include those discussed in Bayer's public reports which are available 
on the Bayer website at The company assumes no liability 
whatsoever to update these forward-looking statements or to conform them to 
future events or developments. 
Emily Hanft, Bayer 416-240-5466 
Ethan Pigott, beSPEAK Communications 416-558-2783 
SOURCE: Bayer Inc. 
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CO: Bayer Inc.
ST: Ontario
-0- Nov/27/2012 13:00 GMT
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