Phase 2 Study for NKTR-102 Will Target Newly-Identified K-Ras Mutated Oncogene Population in Patients with Advanced Colorectal Cancer New Phase 2 Clinical Trials Will Evaluate NKTR-102 in Advanced Breast and Ovarian Cancers
SAN CARLOS, Calif., June 2 /PRNewswire-FirstCall/ -- Nektar Therapeutics
(Nasdaq: NKTR) today announced an expanded Phase 2 development plan for
NKTR-102 (PEG-irinotecan). The company will target newly-characterized
colorectal cancer patients with K-Ras mutated gene status in its Phase 2 study
in advanced colorectal cancer. In addition, NKTR-102 will be evaluated in
Phase 2 trials in two new indications: platinum-refractory ovarian cancer and
advanced breast cancer that is refractory to anthracycline and/or taxane-based
therapies. These studies are expected to commence in the second half of 2008.
Recent data(2) presented at the 2008 American Society of Clinical
Oncologists (ASCO) Annual Meeting shows colorectal cancer (CRC) patients with
tumors that have K-Ras oncogene mutations (K-Ras mutant types) do not respond
to EGFR-inhibitors, such as cetuximab. It is estimated that up to 45% of
colorectal cancer cases have this mutated K-Ras gene. To target this newly-
characterized K-Ras mutant patient population, Nektar will initiate a
prospective study to evaluate the efficacy of NKTR-102 monotherapy in these
patients. The primary endpoint of this randomized trial will be a clinically
meaningful improvement in progression-free survival as compared to standard
irinotecan monotherapy.
"With these recent clinical studies on K-Ras, there is no longer a clear
standard of care for the second-line treatment of advanced colorectal cancer
in patients with the K-Ras gene mutation," said Daniel Haller, M.D., Professor
of Medicine at the Abramson Cancer Center at the University of Pennsylvania.
"This novel oncolytic, NKTR-102, could offer an alternative and promising
approach for tumors in this patient population."
The company also announced new trials for NKTR-102 in breast and ovarian
cancer. These studies will be open-label, single-arm studies to evaluate the
overall response rate (ORR) of NKTR-102 monotherapy in each tumor setting.
The studies will implement a minimax design, known as the Simon design, which
was first proposed by Dr. Richard Simon of the National Cancer Institute in
1989. The two-stage design is routinely used in the evaluation of
oncolytics.(1)
"The promise of NKTR-102 and our small molecule PEGylation platform is
capturing a great deal of attention among oncologists and clinical
investigators," said Howard W. Robin, Nektar President and CEO. "We've seen
significant and repeat anti-tumor activity in our Phase 1 study with NKTR-102.
Our expanded Phase 2 clinical development plan will potentially accelerate our
understanding and development of this novel therapy in multiple cancer types."
Details on the NKTR-102 Phase 2 clinical development plan will be
discussed at an event on June 2, 2008 at 6:30 PM Central time. The event will
be Webcast and can be accessed from the company's website at the following
url: http://www.nektar.com/wt/page/asco.
About NKTR-102 (PEG-irinotecan)
Nektar is developing NKTR-102, a PEGylated form of irinotecan, which was
invented by Nektar using its world-leading small molecule PEGylation
technology platform. The product is currently in a Phase 2a study to evaluate
NKTR-102 in combination with cetuximab.
Irinotecan is an important chemotherapeutic agent used for the treatment
of solid tumors, including colorectal and lung cancers. By applying Nektar's
small molecule PEGylation technology to irinotecan, NKTR-102 may prove to be a
more powerful and tolerable anti-tumor agent. Preclinical studies show that
treatment with NKTR-102 results in significant suppression of tumor growth in
an irinotecan-resistant mouse colorectal tumor model and in similar models of
breast and lung cancer. Administration of NKTR-102 in an animal model also
results in a markedly improved time-concentration profile for SN38, the active
metabolite of irinotecan, as compared to treatment with irinotecan.
Nektar PEGylation technology can enhance the properties of therapeutic
agents by increasing drug circulation time in the bloodstream, decreasing
immunogenicity and dosing frequency, increasing bioavailability and improving
drug solubility and stability. It can also be used to modify pharmaceutical
agents to preferentially target certain systems within the body. It is a
technique in which non-toxic polyethylene glycol (PEG) polymers are attached
to therapeutic agents, and it is applicable to most major drug classes,
including proteins, peptides, antibody fragments, small molecules, and other
drugs. Nektar PEGylation technology is also used in eight additional approved
partnered products in the U.S. or Europe today, including UCB's Cimzia(R) for
Crohn's Disease, Roche's PEGASYS(R) for hepatitis C and Amgen's Neulasta(R)
for neutropenia.
About Nektar
Nektar Therapeutics is a biopharmaceutical company that develops and
enables differentiated therapeutics with its industry-leading PEGylation and
pulmonary drug development technology platforms. Nektar PEGylation and
pulmonary technology, expertise, manufacturing capabilities have enabled eight
approved products for partners, which include the world's leading
pharmaceutical and biotechnology companies. Nektar also develops its own
products by applying its PEGylation and pulmonary technology platforms to
existing medicines with the objective to enhance performance, such as
improving efficacy, safety and compliance.
This press release contains forward-looking statements regarding the
potential of NKTR-102 and the company's PEGylation technology platform. These
forward-looking statements involve important risks and uncertainties,
including but not limited to: (i) preclinical testing and clinical trials for
NKTR-102 are long, expensive and uncertain processes, (ii) because the
NKTR-102 product development programs are in the early phases of clinical
development, the risk of failure is high and can occur at any stage of
development, (iii) the company may fail to obtain regulatory approval of
NKTR-102, (iv) the timing or success of the commencement or conclusion of
NKTR-102 clinical trials is subject to a number of uncertainties including but
not limited to clinical design, patient enrollment, regulatory requirements
and clinical outcomes, (v) potential competition from existing approved
products (branded or generic) or product candidates under development by other
companies could negatively impact the commercial potential of NKTR-102 due to
such common industry competitive factors as efficacy and safety profiles,
pricing, and reimbursement by third party payers, and (vi) the company's
patent applications for NKTR-102 may fail to issue; patents that have issued
may not be enforceable; or unanticipated intellectual property licenses from
third parties may be required in the future. Other important risks and
uncertainties are detailed in the company's reports and other filings with the
SEC including its Quarterly Report on Form 10-Q filed with the SEC on May 9,
2008. Actual results could differ materially from the forward-looking
statements contained in this press release. The company undertakes no
obligation to update forward-looking statements, whether as a result of new
information, future events, or otherwise. No information regarding or
presented at the scientific meetings referred to above (or contained at the
Internet links provided) is intended to be incorporated by reference in this
press release.
Contacts:
Tim Warner (650) 283-4915 or twarner@nektar.com
Stephan Herrera (415) 488-7699 or sherrera@nektar.com
Jennifer Ruddock (650) 631-4954 or jruddock@nektar.com
References and Glossary
1 Simon, Richard, "Optimal Two-Stage Designs for Phase II Clinical
Trials," Controlled Clinical Trials 10:1-10 (1989)
2 E. Van Cutsem, I. Lang, G. D'haens, V. Moiseyenko, J. Zaluski, G.
Folprecht, S. Tejpar, O. Kisker, C. Stroh, P. Rougier, "KRAS status and
efficacy in the first-line treatment of patients with metastatic
colorectal cancer (mCRC) treated with FOLFIRI with or without cetuximab:
The CRYSTAL experience", J Clin Oncol 26: 2008 (May 20 suppl; abstr 2).
SOURCE Nektar Therapeutics
