Roche Announces Positive Results in Solid Tumors Using Human Monoclonal Antibody against IGF-1R (R1507)

http://www.rocheusa.com/newsroom/current/2007/pr2007102302.html

October 23, 2007 — Nutley N.J.
 
Roche Announces Positive Results in Solid Tumors Using Human Monoclonal
Antibody against IGF-1R (R1507)
 
Today, Roche announced positive results from a Phase I trial of R1507,
a human monoclonal antibody to target IGF-1R (insulin-like growth
factor receptor), in patients with solid tumors. IGF-1 is one of the
most potent natural activators of the AKT and MAPK signaling pathways,
which promote cell growth and cell survival. The IGF-1R pathway has
also been shown to have an important role in mediating the resistance
to cytotoxic drugs and EGFR/HER2-targeted agents. The results were
reported during the AACR-NCI-EORTC International Conference on
Molecular Targets and Cancer Therapeutics, held in San Francisco.

Study Results
In the Phase I study, R1507 was administered by intravenous infusion.
Nine of 34 adult patients with advanced solid tumors experienced
disease stabilization. Four of the seven heavily pretreated patients
with Ewing’s sarcoma demonstrated clinical benefit with two of these
patients achieving durable, objective partial responses.

Once a week administration of R1507 was well tolerated with very few
side effects. Treatment with R1507 was not associated with the typical
side-effects normally observed with cancer therapy (e.g., low blood
counts, infection, hair loss, severe nausea and vomiting).  The most
frequent side effects observed were fatigue, anorexia and weight loss,
symptoms that are commonly observed in patients with advanced cancer.

 “We are very encouraged by these early results with R1507 in patients
with refractory Ewing’s sarcoma,” said Kapil Dhingra, MD, Head,
Oncology Disease Biology Area at Roche. “As a result, we have given
this program a very high priority as we believe this molecule has the
potential to be very beneficial in treating patients with sarcoma as
well as a variety of other solid tumors.”

The antibody (R1507) was initially developed under Roche’s broad
antibody development collaboration with Genmab, which began in 2001.

The Phase I study is being conducted at four sites in the U.S.,
including the University of Colorado Cancer Center (Aurora, CO), The
University of Texas M.D. Anderson Cancer Center (Houston, TX), Cancer
Institute of New Jersey (New Brunswick, NJ) and The Institute for Drug
Development (San Antonio, TX).  R1507 has also been investigated in 26
patients on a three week schedule in the Phase I study.  This treatment
schedule was also generally well tolerated with a side effect profile
similar to the weekly schedule.

“This drug attacks the IGF pathway and may provide a new class of drugs
to treat a variety of cancers, including breast, prostate, colon,
melanoma, myeloma and a variety of sarcomas, which could greatly add to
the way that we currently treat these patients,” says Stephen Leong,
M.D., assistant professor of Medical Oncology at the University of
Colorado Cancer Center and lead author of the abstract.

Razelle Kurzrock, MD,  investigator at the M.D. Anderson Cancer Center
and the senior author of the abstract, noted that some of the responses
were very impressive.  For instance, one 28 year-old Ewing’s sarcoma
patient with large tumors unresponsive to many other treatments showed
dramatic tumor shrinkage within six weeks, without side effects.  “This
is one of the best responses I've seen in over 20 years of oncology
experience,” stated Dr. Kurzrock.  

Based on these initial results with R1507, Roche plans to conduct
additional trials and work with a global consortium of sarcoma experts,
including the Sarcoma Alliance for Research through Collaboration
(SARC). “We are very excited about our collaboration with SARC, which
represents a new approach to sarcoma clinical trials, and we look
forward to combining our expertise with that our colleagues at SARC to
expedite new sarcoma treatments,” added Dhingra.

“We are excited to be partnering with Roche on the development of a new
treatment against an important target, which could result in a
potential breakthrough treatment for sarcoma as well as other cancers,”
said Laurence Baker, DO, professor of Medicine and Pharmacology at the
University of Michigan and the Executive Director, SARC. “With Roche’s
considerable expertise in oncology and SARC’s vast network of
physicians and institutions, we look forward to determining the
potential of R1507 in this important disease area.”

About Ewing’s Sarcoma
The Ewing’s family of tumors (EFT) includes primary tumors of bone
(classic Ewing’s sarcoma, primitive neuroectodermal tumor, and Askin
tumor) and extraosseous primary tumors {National Cancer Institute}.
Studies using immunohistochemical markers, cytogenetics, molecular
genetics, and tissue culture indicate that these tumors are all derived
from the same primordial stem cell. EFTs account for 4 percent of
childhood and adolescent malignancies.  The estimated incidence (US) is
approximately 300 new cases per year. The median age for patients with
EFT is 15 years and more than 50 percent of patients are adolescents.
There is a slight male predominance and the lower limbs are affected in
40 percent of the patients.

Approximately 20 to 30 percent of the patients with ETB have overt
metastases at the time of diagnosis. However, outcomes for patients
with metastatic disease have improved little during the last 20 years.
Approximately 25-30 percent survival could be achieved with current
therapies for patients who present with metastatic disease at initial
diagnosis.

About Roche
Hoffmann-La Roche Inc. (Roche), based in Nutley, N.J., is the U.S.
pharmaceuticals headquarters of the Roche Group, one of the world’s
leading research-oriented healthcare groups with core businesses in
pharmaceuticals and diagnostics. For more than 100 years in the U.S.,
Roche has been committed to developing innovative products and services
that address prevention, diagnosis and treatment of diseases, thus
enhancing people's health and quality of life. An employer of choice,
in 2007 Roche was named Top Company of the Year by Med Ad News and one
of the Top 20 Employers (Science magazine). In 2006, Roche was ranked
the    No. 1 Company to Sell For (Selling Power), and one of AARP’s Top
Companies for Older Workers, and in 2005, Roche was named one of
Fortune magazine’s Best Companies to Work For in America. For
additional information about the U.S. pharmaceuticals business, visit
our websites: http://www.rocheusa.com
or www.roche.us.

About SARC
The purpose of the Sarcoma Alliance for Research through Collaboration
(SARC) is to engage all appropriate and necessary resources to cure and
prevent sarcoma.  SARC brings together expert sarcoma researchers and
clinicians from 29 centers of excellence in the United States.  SARC by
the charter, promotes international collaboration in sarcoma clinical
trials through is association with European sarcoma experts.  SARC is
unique as a clinical trial organization in that its trials at the
inception include pediatric and medical patients with sarcoma, because
sarcomas affect people of all ages.  SARC is a 501c3, non-profit
organization that is  headquartered in Ann Arbor, Michigan.

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Contacts:     973-562-2699

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