Incyte Corporation (Nasdaq: INCY) today announced full results from
RECAP, a Phase II trial of ruxolitinib, a JAK1/JAK2 inhibitor, in
combination with capecitabine in second-line metastatic pancreatic
cancer. The findings from this proof-of-concept trial showed that
ruxolitinib plus capecitabine prolonged survival over capecitabine alone
in patients with elevated C-reactive protein (CRP), a well-established
marker of systemic inflammation (hazard ratio = 0.47; 95% CI, 0.26-0.85; P=0.01
(2-sided)). Patients in this subgroup treated with ruxolitinib plus
capecitabine also achieved improvements in other efficacy measures
including objective response rate, clinical benefit response, and weight
gain. These data were presented at the 50th Annual Meeting of
the American Society of Clinical Oncology (ASCO) in Chicago.
Systemic inflammation is commonly observed in patients with advanced
malignancies and has been associated with poor survival.1,2
The majority of patients with pancreatic cancer exhibit evidence of
systemic inflammation, which can be associated with weight loss,
decreased muscle mass, and poor performance status.3 Elevated
CRP, a well characterized, sensitive, and readily measurable marker of
systemic inflammation, has negative prognostic significance in many
human cancers, including pancreatic cancer.4,5,6,7
“Ruxolitinib in combination with capecitabine was generally well
tolerated and exhibited greater clinical activity compared to
capecitabine alone in patients with second-line metastatic pancreatic
cancer and elevated CRP,” said Herbert Hurwitz, M.D., Professor of
Medicine, Duke University School of Medicine, principal investigator of
RECAP who presented the study findings. “Local and systemic inflammation
adversely affect patient outcomes in pancreatic cancer and many other
malignancies. The findings are very encouraging, especially given the
limited treatment options for these patients.”
The RECAP study enrolled 127 patients: 64 randomized to receive
ruxolitinib plus capecitabine and 63 to capecitabine alone. In the
intent-to-treat population, the hazard ratio for overall survival was
0.79 (95% CI, 0.53–1.18; P=0.25 (2-sided)). When patients with
elevated CRP levels were evaluated (n=60), a pre-specified subgroup
based on median CRP at study entry (13 mg/L), the hazard ratio for
overall survival was 0.47 (95% CI: 0.26–0.85; P=0.01 (2-sided)).
In this subgroup, the probability of survival in the ruxolitinib plus
capecitabine group versus the capecitabine alone group at three, six,
and 12 months was 48 percent, 42 percent, and 11 percent versus 29
percent, 11 percent, and 0 percent, respectively; the median time to
death was 83 days in the ruxolitinib plus capecitabine group versus 55
days in the capecitabine alone group with greater differences between
the treatment arms emerging after the median time to death. A post hoc
analysis of overall survival was also conducted using the modified
Glasgow Prognostic Score (mGPS), a well-characterized and prognostically
relevant measure of inflammation in cancer.8 Among patients
in the higher risk categories (mGPS = 1 or 2 corresponding to patients
with CRP >10 mg/L), overall survival favored the
ruxolitinib-capecitabine combination over capecitabine alone (HR = 0.60;
95% CI, 0.35-1.03; P=0.063 (2-sided)).
Similar trends were observed in progression-free survival. The hazard
ratio was 0.75 (95% Cl: 0.51–1.10; P=0.14 (2-sided)) in favor of
ruxolitinib plus capecitabine in the intent-to-treat population, and
0.62 (95% CI: 0.35–1.10; P=0.10 (2-sided)) in the subgroup of
patients with CRP > 13 mg/L. Benefits with ruxolitinib plus capecitabine
treatment were also observed in objective response rate, clinical
benefit response (a composite of improvement in pain intensity,
Karnofsky performance status, analgesia, and weight), and weight gain.
Treatment with ruxolitinib plus capecitabine was generally well
tolerated. Grade ≥3 anemia occurred more frequently in patients treated
with ruxolitinib plus capecitabine (15.3%) compared with those who
received placebo plus capecitabine (1.7%). Grade ≥3 neutropenia and
thrombocytopenia were uncommon in ruxolitinib-treated patients. Grade 3
or 4 non-hematologic adverse events that occurred more frequently with
ruxolitinib plus capecitabine compared with placebo plus capecitabine
included pulmonary embolism (11.9% vs 5.0%), stomatitis (6.8% vs 0%),
and pneumonia (8.5% vs 1.7%). Differences in exposure between treatment
groups (mean of 99.6 days for ruxolitinib plus capecitabine vs 67.4 days
for capecitabine alone) may have contributed to the differences in the
rates of adverse events.
“RECAP provides the first evidence that targeting onco-inflammation
through the JAK-STAT pathway with ruxolitinib may improve survival in
patients with elevated CRP,” said Hervé Hoppenot, President and Chief
Executive Officer, Incyte. “We have initiated a pivotal Phase III
clinical program in patients with mGPS of 1 or 2 to confirm these
findings in pancreatic cancer. We are also investigating the utility of
ruxolitinib in other tumor types in which onco-inflammation plays a key
role.”
The slides used during the presentation can be accessed at 2014
ASCO - RECAP Presentation.
Incyte’s Phase III program in pancreatic cancer includes two
double-blind, placebo-controlled trials focusing on patients with mGPS
of 1 or 2 which is also defined as CRP >10 mg/L: JANUS 1 (NCT02117479)
and JANUS 2 (NCT02119663). Clinical trials evaluating ruxolitinib
activity using mGPS-based patient selection criteria are ongoing in
other solid tumors (colorectal cancer (NCT02119676), non-small cell lung
cancer (NCT02119650), and breast cancer (NCT02120417)).
About the RECAP Trial
The Ruxolitinib Efficacy
and safety in combination with CApecitabine
for subjects with recurrent or treatment refractory metastatic Pancreatic
cancer (RECAP) trial was a Phase II, randomized, double-blind,
placebo-controlled, proof-of-concept trial that investigated ruxolitinib
in combination with capecitabine compared to capecitabine alone as
treatment for metastatic pancreatic cancer. The trial was designed, in
part, to characterize patients with metastatic pancreatic cancer who may
benefit from JAK pathway inhibition with ruxolitinib therapy.
An open-label, run-in period was included to assess the safety of
ruxolitinib plus capecitabine in a cohort of nine patients. After
completion of this run-in period, the randomized, double-blind portion
of the study was conducted. One hundred twenty seven patients were
randomized to one of two treatment arms: ruxolitinib 15 mg twice daily
plus capecitabine 2000 mg/m2, as 1000 mg/m2
twice daily (n=64) or placebo plus capecitabine 2000 mg/m2,
as 1000 mg/m2 twice daily (n=63). Oral ruxolitinib or placebo
was self-administered every day of each 21-day cycle. Capecitabine was
self-administered for the initial 14 days of each cycle. The primary
endpoint of RECAP was overall survival measured from the time of
randomization to the occurrence of death or discontinuation.
About Ruxolitinib
Ruxolitinib is an oral, selective inhibitor of Janus kinases 1 and 2
(JAK1 and JAK2). In the United States, ruxolitinib, brand name Jakafi®,
is indicated for treatment of patients with intermediate or high-risk
myelofibrosis (MF), including primary MF, post-polycythemia vera MF and
post-essential thrombocythemia MF. Jakafi is marketed by Incyte in the
United States and by Novartis as Jakavi® (ruxolitinib)
outside the United States.
Important Safety Information
Jakafi can cause serious side effects including:
Low blood counts: Jakafi may cause your platelet, red blood cell,
or white blood cell counts to be lowered. If you develop bleeding, stop
taking Jakafi and call your healthcare provider. Your healthcare
provider will perform blood tests to check your blood counts before you
start Jakafi and regularly during your treatment. Your healthcare
provider may change your dose of Jakafi or stop your treatment based on
the results of your blood tests. Tell your healthcare provider right
away if you experience unusual bleeding, bruising, fatigue, shortness of
breath, or a fever.
Infection: You may be at risk for developing a serious infection
while taking Jakafi. Tell your healthcare provider if you develop
symptoms such as chills, nausea, vomiting, aches, weakness, fever, or
painful skin rash or blisters.
The most common side effects of Jakafi include dizziness and headache.
These are not all the possible side effects of Jakafi. Ask your
healthcare provider or pharmacist for more information. Tell your
healthcare provider about any side effect that bothers you or that does
not go away.
Before taking Jakafi, tell your healthcare provider about all the
medications, vitamins, and herbal supplements you are taking and all
your medical conditions, including if you have an infection, have or had
liver or kidney problems, are on dialysis, or have any other medical
condition. Do not drink grapefruit juice while taking Jakafi.
Women should not take Jakafi while pregnant or planning to become
pregnant, or if breast-feeding.
Please see the Full Prescribing Information available at www.jakafi.com,
which includes a more complete discussion of the risks associated with
Jakafi.
About the Webcast
Incyte will host an investor meeting, which will be webcast live at 6:45
p.m. CDT on June 2, 2014, and can be accessed at www.incyte.com
under Investor Relations, Events and Webcasts. A replay of the event
will be available for 60 days.
About Incyte
Incyte Corporation is a Wilmington, Delaware-based biopharmaceutical
company focused on the discovery, development and commercialization of
proprietary small molecule drugs, primarily in oncology. For additional
information on Incyte, please visit the Company’s website at www.incyte.com.
Forward-Looking Statements
Except for the historical information set forth herein, the matters set
forth in this press release, including without limitation statements
with respect to the potential efficacy, safety and therapeutic value of,
and Incyte’s plans for, ruxolitinib in pancreatic cancer and other solid
tumors, including that ruxolitinib may improve survival in patients with
elevated CRP, contain predictions and estimates and are forward-looking
statements within the meaning of the "safe harbor" provisions of the
Private Securities Litigation Reform Act of 1995. These forward-looking
statements are based on Incyte’s current expectations and subject to
risks and uncertainties that may cause actual results to differ
materially, including unanticipated developments in and risks related to
the efficacy or safety of ruxolitinib, the results of further research
and development, the high degree of risk and uncertainty associated with
drug development, clinical trials and regulatory approval processes,
other market or economic factors, competitive and technological
advances, and other risks detailed from time to time in Incyte's filings
with the Securities and Exchange Commission, including its Quarterly
Report on Form 10-Q for the quarter ended March 31, 2014. Incyte
disclaims any intent or obligation to update these forward-looking
statements.
References
1 Hanahan D, Coussens LM. Cancer Cell. 2012;21:309-22.
2
Seruga B, et al. Nat Rev Cancer. 2008;8:887–99.
3
Fearon KC, et al. World J Surg. 1999;23:584-8.
4
McMillan DC, et al. Nutr Cancer. 2001;41:64-9.
5
Al Murri, et al. Br J Cancer. 2006;94:227-30.
6
Proctor MJ, et al. Br J Cancer. 2010;103:870-6.
7
McMillan DC. Cancer Treat Rev. 2013;39:534-40.
8
McMillan DC, et al. Int J Colorectal Dis. 2007;22:881-6.
Copyright Business Wire 2014