Geron Initiates Randomized Phase 2 Clinical Trial of Imetelstat in Breast Cancer
Telomerase Inhibitor in Combination with Chemotherapy Targets Cancer Stem Cells
MENLO PARK, Calif., Dec 02, 2010 (BUSINESS WIRE) -- Geron Corporation (GERN)
today announced enrollment of the first patient in a randomized Phase 2 clinical
trial of its telomerase inhibitor drug, imetelstat (GRN163L), in combination with
paclitaxel (with or without bevacizumab) in patients with locally recurrent or
metastatic breast cancer.
"We are pleased to initiate our second randomized Phase 2 clinical trial of
imetelstat," said Stephen M. Kelsey, M.D., Geron's executive vice president and
chief medical officer, oncology. "We are applying what we learned in our Phase 1
program and leveraging our preclinical data that showed imetelstat's activity
against cancer stem cells from a broad range of tumor types, including breast
cancer."
"We look forward to assessing imetelstat in this Phase 2 clinical trial in breast
cancer," said Kathy D. Miller, M.D., Associate Professor and Sheila D. Ward
Scholar at the Indiana University Melvin and Bren Simon Cancer Center and lead
investigator of the trial. "The Phase 1 trial of imetelstat combined with
paclitaxel and bevacizumab in locally recurrent or metastatic breast cancer
showed an encouraging preliminary response rate, particularly in context of the
reduced doses of chemotherapy that were administered during treatment cycles."
Phase 2 Trial Design
The clinical trial is an open label, multi-center, randomized Phase 2 study of
the efficacy and safety of treatment with imetelstat plus paclitaxel (with or
without bevacizumab) versus paclitaxel (with or without bevacizumab) for patients
with locally recurrent or metastatic breast cancer (MBC) who have not received
chemotherapy or have received one non-taxane based chemotherapy for MBC.
The primary efficacy endpoint for this Phase 2 trial is to estimate
progression-free survival (PFS) for patients receiving imetelstat in addition to
paclitaxel with or without bevacizumab. Secondary efficacy endpoints are
objective response rate and clinical benefit of imetelstat when added to
paclitaxel with or without bevacizumab. Safety and tolerability will also be
assessed.
Patients eligible for the trial are randomly assigned in a 1:1 ratio to receive
either imetelstat in addition to paclitaxel or paclitaxel only. Patients may
receive bevacizumab based on the investigator's decision and drug availability to
the patient, but bevacizumab therapy is not required. Patients in the trial will
be stratified based on two parameters: (1) whether bevacizumab is used in
combination with paclitaxel; and (2) line of therapy (first line versus second
line). Imetelstat is administered at a dose of 300 mg/m(2) on day one of a 21 day
treatment cycle. Paclitaxel is administered at 90 mg/m(2) on days one and eight
and bevacizumab is administered at 15 mg/kg on day one of the 21 day cycle. The
dose and dosing schedule of imetelstat was established during the Phase 1
clinical trial of imetelstat in combination with paclitaxel and bevacizumab in
locally advanced or MBC.
Enrollment is estimated at 150 patients at approximately 80 clinical sites across
the U.S. and Canada.
Rationale for the Trial
Results from Phase 1 clinical trials using imetelstat have documented
imetelstat's safety profile. Data from preclinical studies have demonstrated
imetelstat's activity against bulk breast cancer cells as well as breast cancer
stem cells.
The prior Phase 1 clinical trial testing the safety of imetelstat in combination
with paclitaxel and bevacizumab in patients with locally recurrent or MBC showed
an objective response rate of 53.8% (95% confidence interval:28.7% to 77.6%)
despite reduced doses of paclitaxel and/or imetelstat in the majority of
patients. Median response duration was 21.7 weeks (7.3 to 48.3 weeks). These data
provided the rationale for conducting the current Phase 2 study.
The Phase 2 dose and dosing schedule of 300 mg/m(2) of imetelstat on day one of a
21 day treatment cycle was selected to achieve extended exposures to imetelstat
that exceed the levels that have been associated with efficacy in xenograft
models of human cancers, while minimizing hematological toxicities.
In addition, previously published in vitro studies showed that imetelstat
synergizes with paclitaxel in inhibiting the growth of breast cancer cells.
Synergy between imetelstat and bevacizumab was demonstrated in a xenograft model
of human breast cancer.
Breast Cancer Stem Cells
Cancer stem cells are rare populations of malignant cells with the capacity for
endless self-renewal because of high telomerase activity. Cancer stem cells are
believed to be responsible for tumor growth, recurrence and metastasis. Their
resistance to chemotherapy and conventional anti-cancer agents make them
important targets for novel therapies. By inhibiting breast cancer stem cells,
the use of imetelstat in combination with standard debulking chemotherapy, such
as paclitaxel, may result in a more durable tumor response than with chemotherapy
alone.
Breast cancer stem cell function was inhibited by imetelstat in preclinical
models. Imetelstat treatment of breast cancer cells in vitro led to inhibition of
self-renewal capacity and cell death. In animal models of human breast cancer,
imetelstat treatment reduced the formation of new tumors by 50%. These data were
published by Geron scientists and collaborators in the November 15, 2010 issue of
Cancer Research.
About Breast Cancer
Breast cancer is the most frequent cancer affecting women worldwide and remains
the leading cause of cancer death among women. In 2007, an estimated 1.3 million
new cases of breast cancer were diagnosed and an estimated 468,000 breast
cancer-related deaths occurred. The highest incidence of breast cancer is in the
United States, where, in 2010, an estimated 207,090 new cases will be diagnosed
in women and 1,940 in men, and an estimated 40,230 people will die of the disease
(American Cancer Society, Cancer Facts and Figures 2010).
About Telomerase and Imetelstat (GRN163L)
Telomerase is a critical and broadly applicable tumor target. The enzyme is
expressed in a wide range of malignant tumors, and its activity is essential for
the indefinite replicative capacity of cancer that enables malignant cell growth.
Telomerase has now also been shown to be a target of cancer stem cells.
Telomerase is absent or expressed only transiently at low levels in most normal
adult tissues.
Imetelstat is a lipidated short chain oligonucleotide that binds with high
affinity and specificity to the catalytic site of telomerase, resulting in
competitive inhibition of enzyme activity. Proprietary manufacturing chemistry
and the addition of a 5' lipid chain have enabled the molecule to penetrate cells
and tissues throughout the body.
Imetelstat has demonstrated anti-tumor effects in a wide range of preclinical
xenograft models of human solid and hematological tumors, and potent activity
against cancer stem cells derived from primary patient samples or cancer cell
lines from multiple tumor types.
Imetelstat has been tested in six Geron-sponsored Phase 1 clinical trials at 22
U.S. medical centers treating over 180 patients examining the safety,
tolerability, pharmacokinetics and pharmacodynamics of the drug, alone or in
combination with other standard therapies, in patients with different
hematological and solid tumors.
A randomized Phase 2 clinical trial of imetelstat has been initiated in non-small
cell lung cancer. Two single arm Phase 2 clinical trials are planned in multiple
myeloma and essential thrombocythemia. All are malignancies in which cancer stem
cells are believed to play an important role in relapse after standard therapy.
About Geron
Geron is developing first-in-class biopharmaceuticals for the treatment of cancer
and chronic degenerative diseases, including spinal cord injury, heart failure
and diabetes. The company is advancing an anti-cancer drug and a cancer vaccine
that target the enzyme telomerase through multiple Phase 2 clinical trials in
different cancers. For more information, visit geron.com.
This news release may contain forward-looking statements made pursuant to the
"safe harbor" provisions of the Private Securities Litigation Reform Act of 1995.
Investors are cautioned that statements in this press release regarding potential
applications of Geron's telomerase and oncology technology constitute
forward-looking statements that involve risks and uncertainties, including,
without limitation, risks inherent in the development and commercialization of
potential products, uncertainty of clinical trial results or regulatory approvals
or clearances, need for future capital, dependence upon collaborators and
protection of our intellectual property rights. Actual results may differ
materially from the results anticipated in these forward-looking statements.
Additional information on potential factors that could affect our results and
other risks and uncertainties are detailed from time to time in Geron's periodic
reports, including the quarterly report on Form 10-Q for the quarter ended
September 30, 2010 and quarterly report on Form 10-K for the year ended December
31, 2009.
SOURCE: Geron Corporation
Geron Corporation
Anna Krassowska, Ph.D., 650-473-7765
Investor and Media Relations
info@geron.com
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Steady progress.
Best,
S. |
