Data Show High Rates of Objective Tumor Regression, AFP Response and
Encouraging Progression-Free and Overall Survival
Exelixis, Inc. (NASDAQ:EXEL) today reported positive updated interim
data from the cohort of hepatocellular carcinoma (HCC) patients
participating in the ongoing phase 2 randomized discontinuation trial
(RDT) of cabozantinib. Chris Verslype, M.D., Ph.D., professor of
medicine at the Departments of Digestive Oncology/Hepatology at the
University Hospitals Gasthuisberg, Leuven, Belgium, and an investigator
on the trial, presented the data today in an oral session at the
American Society of Clinical Oncology 2012 Annual Meeting (Abstract
#4007). The meeting is taking place in Chicago, Illinois. Slides from
the presentation are available at http://www.exelixis.com/resources/events/asco-2012.
The results comprise data from 41 patients with advanced hepatocellular
carcinoma with measurable disease at baseline and documented progressive
disease per RECIST criteria. Patients in the open label 12-week Lead-In
Stage of the trial received a daily dose of 100 mg cabozantinib.
Eligible patients had Child-Pugh Score A. Eighty percent had received
1-2 prior lines of systemic therapy: 56% had prior tyrosine kinase
inhibitor (TKI) therapy, including 51% previously treated with
sorafenib. At baseline, extrahepatic spread of disease (which is
associated with a poorer prognosis) was present in 73% of subjects, 39%
had hemoglobin (Hb) < 11 g/dL, 34% had thrombocytopenia, and median
alpha-fetoprotein (AFP) level was 368 ng/ml. Tumor assessments per
original RECIST 1.0 were conducted using conventional CT/MRI at baseline
and every 6 weeks thereafter.
Progression-Free survival (PFS) and Overall
Survival (OS). Median PFS was 4.4 months, and was similar for
sorafenib-pretreated and sorafenib-naïve patients. Median OS in the 41
patients was 15.1 months.
Response Rate. The week 12 disease control
rate (partial response [PR] and stable disease [SD] at week 12) was 66%.
Evidence of objective tumor regression was observed in 78% of patients,
including those with or without prior sorafenib therapy. The best
radiologic response per RECIST in the Lead-In stage of the study for 36
patients with at least one post-baseline measurement was PR in 2
patients (5%) and SD in 32 patients (78%).
"The progression-free survival and overall survival results observed to
date are encouraging," said Eric Van Cutsem, M.D., Ph.D., professor of
internal medicine and digestive oncology at the University Hospitals
Gasthuisberg, Leuven, Belgium, and senior investigator on the
presentation. "It is also interesting that the activity of cabozantinib
in this population was irrespective of sorafenib pre-treatment status.
The data suggest that dual inhibition of MET and VEGF with cabozantinib
may provide clinical benefit beyond what can be achieved through
inhibition of either pathway alone."
AFP Biomarker and hemoglobin. A decrease of
>50% in serum AFP was observed in 9 of 26 patients (35%) with baseline
values ? 20 ng/mL The median maximum rise in Hb for the 13 patients with
baseline Hb < 11 g/dL was 3.1 g/dL (range 1.3 to 7.8 g/dL).
"These interim data are encouraging and support the potential utility of
cabozantinib in the treatment of HCC," said Michael M. Morrissey, Ph.D.,
president and chief executive officer of Exelixis. "As previously
announced, a trial evaluating cabozantinib in a second-line randomized
phase 2 trial in HCC is planned under our Cooperative Research and
Development Agreement with the National Cancer Institute's Cancer
Therapy Evaluation Program. We believe this planned trial will help to
prioritize the development of cabozantinib in HCC in the context of the
multiple indications in which the compound appears to provide clinical
The tolerability of cabozantinib in patients with HCC was similar to
that of other TKIs. The most frequently reported adverse events (AEs) of
grade ? 3, regardless of causality in the 41 patients in the HCC cohort
were: diarrhea (20%), hand-foot syndrome (15%), thrombocytopenia (15%),
aspartate aminotransferase increased (10%), asthenia (7%), hypertension
(7%), fatigue (10%), nausea (2%), vomiting (2%), and weight decreased
(2%). There were no grade 5 events related to cabozantinib and no
clinically significant bleeding was reported.
Randomized Discontinuation Trial Design
The presented data above are from the HCC cohort from the randomized
discontinuation trial evaluating the activity of cabozantinib in
multiple tumor types. In the RDT design, patients initially receive open
label cabozantinib at 100 mg daily (free base equivalents, corresponding
to 125 mg salt form) during a 12-week Lead-In Stage, which evaluates the
effects of uninterrupted cabozantinib administration. Patients achieving
a PR per RECIST criteria at week 12 are eligible for continued open
label treatment with cabozantinib, and patients with progressive disease
discontinue treatment. Patients with SD enter the randomized
discontinuation phase, which assesses the progression free survival of
these patients after randomization and blinded allocation to placebo vs.
cabozantinib. Patients progressing on placebo have the option of
receiving salvage therapy with cabozantinib.
Cabozantinib is a potent targeted therapy that inhibits MET and VEGFR2.
Cabozantinib is an investigational agent that provides coordinated
inhibition of metastasis and angiogenesis to kill tumor cells while
blocking their escape pathways. The therapeutic role of cabozantinib is
currently being investigated across several tumor types. MET is
upregulated in many tumor types, thus facilitating tumor cell escape by
promoting the formation of more aggressive phenotypes, resulting in
metastasis. MET-driven metastasis may be further stimulated by hypoxic
conditions in the tumor environment, which are often exacerbated by
selective VEGF-pathway inhibitors. In preclinical studies, cabozantinib
has shown powerful tumoricidal, antimetastatic and antiangiogenic
Extensive apoptosis of malignant cells
Decreased tumor invasiveness and metastasis
Decreased tumor and endothelial cell proliferation
Blockade of metastatic bone lesion progression
Disruption of tumor vasculature
Exelixis, Inc. is a biotechnology company committed to developing small
molecule therapies for the treatment of cancer. Exelixis is focusing its
proprietary resources and development efforts exclusively on
cabozantinib (XL184), its most advanced product candidate, in order to
maximize the therapeutic and commercial potential of this compound.
Exelixis believes cabozantinib has the potential to be a high-quality,
broadly-active, differentiated pharmaceutical product that can make a
meaningful difference in the lives of patients. Exelixis has also
established a portfolio of other novel compounds that it believes have
the potential to address serious unmet medical needs, many of which are
being advanced by partners as part of collaborations. For more
information, please visit the company's web site at www.exelixis.com.
This press release contains forward-looking statements, including,
without limitation, statements related to: the continued development and
clinical, therapeutic and commercial potential of, and opportunities
for, cabozantinib; the belief that the referenced data are encouraging
and suggest that dual inhibition of MET and VEGF with cabozantinib may
provide clinical benefit beyond what can be achieved through inhibition
of either pathway alone; the potential utility of cabozantinib in the
treatment of HCC; and the referenced planned randomized phase 2 trial of
cabozantinib in HCC and the expected benefits of such planned trial.
Words such as "demonstrates," "positive," "encouraging," "suggest,"
"may," "can," "support," "planned," "believe," "will" "potential," and
similar expressions are intended to identify forward-looking statements.
These forward-looking statements are based upon Exelixis' current plans,
assumptions, beliefs and expectations. Forward-looking statements
involve risks and uncertainties. Exelixis' actual results and the timing
of events could differ materially from those anticipated in such
forward-looking statements as a result of these risks and uncertainties,
which include, without limitation: risks related to the potential
failure of cabozantinib to demonstrate safety and efficacy in clinical
testing; Exelixis' ability to conduct clinical trials of cabozantinib
sufficient to achieve a positive completion; the availability of data at
the referenced times; the sufficiency of Exelixis' capital and other
resources; the uncertain timing and level of expenses associated with
the development of cabozantinib; the uncertainty of the FDA approval
process; timely receipt of potential reimbursements, milestones,
royalties and profits under Exelixis' collaborative agreements;
Exelixis' ability to enter into new collaborations; market competition;
and changes in economic and business conditions. These and other risk
factors are discussed under "Risk Factors" and elsewhere in Exelixis'
quarterly report on Form 10-Q for the quarter ended March 30, 2012 and
Exelixis' other filings with the Securities and Exchange Commission.
Exelixis expressly disclaims any duty, obligation or undertaking to
release publicly any updates or revisions to any forward-looking
statements contained herein to reflect any change in Exelixis'
expectations with regard thereto or any change in events, conditions or
circumstances on which any such statements are based.
Charles Butler, 650-837-7277
Relations and Corporate Communications