-- Study met its primary endpoint with a 38% objective response rate
SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)--May 31, 2015--
Exelixis Inc. (NASDAQ:EXEL) today announced positive results from a
two-stage phase 2 investigator-sponsored trial (IST) evaluating
cabozantinib in patients with advanced RET-rearranged lung cancers. Data
were reported for the first stage, which enrolled 16 patients. The
objective response rate (ORR) was 38% (6/16), with a median duration of
response of 8 months. Although the trial is still accruing, it has
already met its primary endpoint, exceeding the predefined targeted
number of five objective responses. Alexander Drilon, M.D. of New York’s
Memorial Sloan Kettering Cancer Center (MSKCC) will present the data
(Abstract #8007) today during an oral abstract session at the 2015
Annual Meeting of the American Society of Clinical Oncology in Chicago,
“Constitutive activation of receptor tyrosine kinases by mutation or
rearrangement is an oncogenic event in a substantial proportion of
patients with non-small cell lung cancer (NSCLC), and includes the
activation of RET by gene rearrangement in about 1-2% of patients with
adenocarcinoma histology,” said Dr. Drilon, the study’s principal
investigator. “Cabozantinib is an active therapy in RET-rearranged lung
cancers, as demonstrated by the durable objective responses observed in
the first stage of this study. While this trial continues to accrue
patients to complete its second stage, it has already met its primary
endpoint. Further investigation is clearly warranted.”
Michael M. Morrissey, Ph.D., president and chief executive officer of
Exelixis, commented on the results: “Exelixis is committed to working
with independent investigators, and with our collaborators at the
National Cancer Institute’s Cancer Therapy Evaluation Program, to fully
evaluate cabozantinib’s potential in a variety of disease settings
beyond our company-sponsored pivotal trials in renal and liver cancers.
The data in RET-rearranged NSCLC are compelling, and we look forward to
discussing with our collaborators potential next steps for cabozantinib
in this setting.”
This single-institution, open-label phase 2 trial evaluates cabozantinib
in patients with advanced RET-rearranged NSCLC, including the KIF5B-RET
fusion, the most common rearrangement. Eligible patients must have stage
IV lung cancer (with RET rearrangement confirmed by break apart
fluorescence in situ hybridization and/or next generation sequencing),
Karnofsky Performance Status greater than 70 percent, and measurable
disease per RECIST 1.1. Patients receive 60 mg daily cabozantinib in
28-day cycles until disease progression or unacceptable toxicity.
The trial is designed to enroll a maximum of 25 patients in two stages.
The first stage of the trial, the subject of today’s data presentation,
enrolled 16 patients, and one partial response was required to expand
the trial into its second stage that will enroll an additional nine
The primary endpoint of the trial is ORR, with five partial responses
(PRs) required to meet the endpoint. Secondary endpoints include
response rate at 12 weeks, progression-free survival (PFS), overall
survival (OS), and toxicity.
At the time of data cut-off, 20 patients had been treated and 18 were
evaluable. Data were presented for the 16 patients enrolled in the first
stage of the trial. The median age for patients in the first stage of
the trial was 59 (range 38-80 years), and 62 percent (10/16) of these
were female. All patients in the first stage had adenocarcinoma, the
median number of prior lines of chemotherapy was 1, and 31% of patients
had received ≥ 2 lines of prior chemotherapy.
Sixteen patients from the first stage of the trial were evaluable for
tumor response. ORR, the primary endpoint of the trial, was 38%, with
six confirmed PRs recorded. The median duration of response was 8 months
(range 5.5-26 months) including one patient with a confirmed partial
response who remained on treatment more than 25 months. One patient with
a best response of stable disease remained on cabozantinib treatment for
more than 21 months. ORR at 12 weeks, a secondary endpoint, was 36%,
with five confirmed PRs recorded among the 14 patients evaluable at 12
PFS and OS are secondary endpoints. The median PFS was 7 months (95% CI
5-NA). The median OS was 10 months (95% CI 8-NA) with a median follow-up
of 24 months.
Grade 3 adverse events deemed related to study drug by the investigators
were thrombocytopenia (19%), increased lipase (13%), increased AST,
hypophosphatemia, fatigue, oral mucositis, palmar plantar
erthrodysesthesia, hypertension, and retroperitoneal hematoma (all 6%).
Half of the patients (8/16) experienced one dose reduction to 40 mg
during the course of therapy, with 19% (3/16) reducing to 20 mg daily.
One patient discontinued therapy secondary to a grade 3 retroperitoneal
hemorrhage, and there was one death unrelated to drug (grade 5
respiratory failure [post-thoracentesis]).
Cabozantinib inhibits the activity of tyrosine kinases including MET,
VEGFRs and RET. These receptor tyrosine kinases are involved in both
normal cellular function and in pathologic processes such as
oncogenesis, metastasis, tumor angiogenesis, and maintenance of the
COMETRIQ® (cabozantinib) is currently approved by the U.S. Food and Drug
Administration for the treatment of progressive, metastatic medullary
thyroid cancer (MTC).
The European Commission granted COMETRIQ conditional approval for the
treatment of adult patients with progressive, unresectable locally
advanced or metastatic MTC. Similar to another drug approved in this
setting, the approved indication states that for patients in whom
Rearranged during Transfection (RET) mutation status is not known or is
negative, a possible lower benefit should be taken into account before
individual treatment decisions.
Important Safety Information, including Boxed WARNINGS
WARNING: PERFORATIONS AND FISTULAS, and HEMORRHAGE
Serious and sometimes fatal gastrointestinal perforations and
fistulas occur in COMETRIQ-treated patients.
Severe and sometimes fatal hemorrhage occurs in COMETRIQ-treated
COMETRIQ treatment results in an increase in thrombotic events, such
as heart attacks.
Wound complications have been reported with COMETRIQ.
COMETRIQ treatment results in an increase in hypertension.
Osteonecrosis of the jaw has been observed in COMETRIQ-treated
Palmar-Plantar Erythrodysesthesia Syndrome (PPES) occurs in patients
treated with COMETRIQ.
The kidneys can be adversely affected by COMETRIQ. Proteinuria and
nephrotic syndrome have been reported in patients receiving COMETRIQ.
Reversible Posterior Leukoencephalopathy Syndrome has been observed
Avoid administration of COMETRIQ with agents that are strong CYP3A4
inducers or inhibitors.
COMETRIQ is not recommended for use in patients with moderate or
severe hepatic impairment.
COMETRIQ can cause fetal harm when administered to a pregnant woman.
Adverse Reactions – The most commonly reported adverse drug reactions
(≥25%) are diarrhea, stomatitis, palmar-plantar erythrodysesthesia
syndrome (PPES), decreased weight, decreased appetite, nausea, fatigue,
oral pain, hair color changes, dysgeusia, hypertension, abdominal pain,
and constipation. The most common laboratory abnormalities (≥25%) are
increased AST, increased ALT, lymphopenia, increased alkaline
phosphatase, hypocalcemia, neutropenia, thrombocytopenia,
hypophosphatemia, and hyperbilirubinemia.
Please see full U.S. prescribing information, including Boxed WARNINGS,
Please refer to the full European Summary of Product Characteristics for
full European Union prescribing information, including contraindication,
special warnings and precautions for use at www.sobi.com
Exelixis, Inc. is a biopharmaceutical company committed to developing
small molecule therapies for the treatment of cancer. Exelixis is
focusing its development and commercialization efforts primarily on
COMETRIQ® (cabozantinib), its wholly-owned inhibitor of multiple
receptor tyrosine kinases. Another Exelixis-discovered compound,
cobimetinib, a highly selective inhibitor of MEK, is being evaluated by
Roche and Genentech (a member of the Roche Group) in a broad development
program under a collaboration with Exelixis. 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: future data presentations for
the phase 2 IST evaluating cabozantinib in patients with advanced
RET-rearranged lung cancers; potential future evaluation of cabozantinib
in NSCLC; the continued development and clinical, therapeutic and
commercial potential of, and opportunities for, cabozantinib in a
variety of disease settings; and Exelixis’ commitment to working with
independent investigators and collaborators at the National Cancer
Institute’s Cancer Therapy Evaluation Program to evaluate such potential
and discuss the potential next steps for cabozantinib in NSCLC. Words
such as “will,” “continues,” “further,” “committed,” “potential,” “look
forward,” “next steps,” or other similar expressions, identify
forward-looking statements, but the absence of these words does not
necessarily mean that a statement is not forward-looking. In addition,
any statements that refer to expectations, projections or other
characterizations of future events or circumstances are forward-looking
statements. These forward-looking statements are based upon Exelixis’
current plans, assumptions, beliefs, expectations, estimates and
projections. Forward-looking statements involve risks and uncertainties.
Exelixis’ actual results and the timing of events could differ
materially from those anticipated in the forward-looking statements as a
result of these risks and uncertainties, which include, without
limitation: the availability of data at the expected times; risks
related to the potential failure of cabozantinib to demonstrate safety
and efficacy in clinical testing; the clinical, therapeutic and
commercial value of cabozantinib; the uncertain timing and level of
expenses associated with the development of cabozantinib; Exelixis’
ability and the ability of its collaborators to conduct clinical trials
of cabozantinib sufficient to achieve a positive completion; market
competition; changes in economic and business conditions; and other
factors discussed under the caption “Risk Factors” in Exelixis’
quarterly report on Form 10-Q filed with the Securities and Exchange
Commission (SEC) on April 30, 2015 and in Exelixis’ other filings with
the SEC. The forward-looking statements made in this press release speak
only as of the date of this press release. 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
Exelixis, the Exelixis logo, and COMETRIQ are registered U.S.
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Source: Exelixis Inc.
Investor Relations and Corporate
For Exelixis, Inc.