OSI Pharmaceuticals, Inc. (NASDAQ: OSIP) announced today
preliminary data from two Phase I dose escalation studies of oral
OSI-906, a small molecule insulin-like growth factor-1 receptor
(IGF-1R) tyrosine kinase inhibitor, in patients with advanced solid
tumors. The studies, along with a third on-going Phase I trial
assessing OSI-906 in combination with Tarceva, comprise part of the
Company�s principal oncology development program targeting the
IGF-1R. The program also includes translational research and
biomarker development activities around this highly attractive
oncology target. In an intermittent oral dosing study, OSI-906 was
well-tolerated up to doses of 450mg and has provided preliminary
evidence of anti-tumor activity, with one confirmed partial
response in an adrenocortical carcinoma (ACC) patient; one minor
response in a patient with non-small cell lung cancer (NSCLC); 14
patients with stabilization of their disease for longer than 12
weeks including 7 patients with stabilization of their disease for
longer than 24 weeks (out of 27 patients evaluable for tumor
response to date). In a continuous dosing study, OSI-906 also had
an acceptable safety profile and disease stabilization for longer
than 12 weeks has been observed in 8 out of 29 patients evaluable
for tumor response to date. Both Phase I studies continue to accrue
patients at higher doses to determine the maximum tolerated dose
(MTD) for both intermittent and continuous dosing of OSI-906, and
to establish a recommended dose and dosing schedule for a Phase II
clinical trial of OSI-906.
�We believe these data, along with early data from an additional
combination Phase I study with Tarceva, continue to position
OSI-906 as a potential first-in-class small molecule inhibitor of
the IGF-1R,� stated Colin Goddard, Ph.D., Chief Executive Officer
of OSI Pharmaceuticals. �Our extensive research around this crucial
oncology signaling target has led us to develop a comprehensive
development effort that includes targeting tumors such as ACC and
ovarian cancer, where IGF-2 over-expression could indicate a
particular dependence on this signaling pathway, and also NSCLC,
where our understanding of EMT and compensatory signaling mechanism
suggest that a Tarceva/OSI-906 combination could be particularly
effective. With continued progress in our program we believe we
could begin two registration-oriented trials � a monotherapy study
in ACC in 2009 and a Tarceva combination study in NSCLC in
2010.�
The OSI-906 Phase I single-agent data will be presented in two
poster presentations at the Annual Meeting of the American Society
of Clinical Oncology (ASCO) in Orlando, FL on May 30, 2009 between
8 a.m. and noon EDT (Abstracts #3544 and #2559).
Study Results
Preliminary activity in adrenocortical tumor (ACC) in phase I
dose escalation study of intermittent oral dosing of OSI-906, a
small molecule insulin like growth factor -1 receptor (IGF-1R)
tyrosine kinase inhibitor in patients with advanced solid tumors-
C.P. Carden, et al. (Abstract #3544)
The primary objective of this study (OSI-906-102) is to
determine the maximum tolerated dose (MTD) and recommended Phase II
dose of oral OSI-906 for three intermittent dosing schedules:
Schedule 1: days 1-3, every 14 days; Schedule 2: days 1-5, every 14
days; Schedule 3: days 1-7, every 14 days. Secondary objectives
include safety profile, pharmacokinetics (PK) and pharmacodynamics
(PD) profiles and preliminary anti-tumor activity.
Preliminary results from 33 patients evaluable to date showed
that OSI-906 was well-tolerated up to doses of 450mg, with no dose
limiting toxicities (DLTs) and no grade 3 or 4 toxicities reported
to date. Most common adverse events were grade 1 rash, diarrhea,
fatigue and peripheral edema. Frequency and severity of toxicities
did not correlate with dose level. Two cases of hyperglycemia (one
grade 1; one grade 2) were reported.
Encouraging anti-tumor activity was seen in the study, with one
partial response in an ACC patient at the 450mg dose (in the
Schedule 1 group), 14 patients with stable disease for ? 12 weeks
including 7 patients with stable disease for ? 24 weeks. Of
particular note, anti-tumor activity was seen in two ACC patients
and one NSCLC patient:
- One 2nd-line ACC patient, a
35-year old woman with metastatic disease, had a partial response
(PR) confirmed at 16 weeks of treatment with OSI-906. No
drug-related toxicities have been observed to date and this patient
continues on therapy.
- One 4th-line NSCLC patient, a
77-year old man with metastatic disease, had a minor response per
the treating physician and a best response (per RECIST) of stable
disease for 43 weeks.
- One 3rd-line ACC patient had
stable disease for 30 weeks.
The study authors also note that PK is dose-proportional up to
450mg. An exploratory analysis from glucose monitoring also
indicates that significant hyperglycemia was not observed in
patients in spite of hyperinsulinemia at higher doses.
The MTD in this study has not yet been reached and patient
accrual is on-going.
Phase I dose escalation study of continuous oral dosing of
OSI-906, an insulin like growth factor-1 receptor (IGF-1R) tyrosine
kinase inhibitor, in patients with advanced solid tumors- C.R.
Lindsay, et al. (Abstract #2559)
The primary objective of this study (OSI-906-101) is to
determine the MTD and recommended Phase II dose of oral OSI-906
administered either once daily or twice daily. Secondary objectives
also included safety profile, PK and PD profiles and preliminary
anti-tumor activity.
Preliminary results from 37 patients with advanced solid tumors
(9 colorectal, 6 pancreatic, 3 renal, 3 esophageal and 16 other
tumor types) also show that continuous oral dosing of OSI-906,
given either once or twice a day, has an acceptable safety profile.
One recent DLT of asymptomatic grade 3 hyperglycemia was reported
at the 450mg once-a-day dose, however, this patient was
asymptomatic and glucose returned to normal by Day 2, and no dose
interruptions or reductions were necessary. OSI-906 plasma
concentrations exceed concentration required for anti-tumor
efficacy in preclinical models, with twice-a-day dosing providing
improved coverage above threshold. Further, PD target modulation
and disease stabilization were observed. While no objective tumor
responses have been reported to date, 8 patients had stable disease
? 12 weeks including 4 patients who had stable disease ? 24
weeks.
The MTD in this study has not yet been reached and patient
accrual is on-going.
Additional Background on
OSI-906
IGF-1 and IGF-2 are growth factors, or hormones, known to
stimulate growth and survival of cancerous cells. IGF-1R has been
viewed as an important therapeutic target due to its involvement in
the growth and proliferation of a variety of human cancers,
including colorectal, prostate, non-small cell lung, breast and
ovarian cancers.
In preclinical studies, OSI-906 blocked the ability of IGF-1R to
signal in xenograft mouse models of human colorectal cancer.
Preclinical research also showed that colon cancer tumor cells
respond to OSI-906 because they produce and are dependent on the
growth-promoting effects of IGF-2. In addition to colorectal
cancer, OSI-906 has also been shown to inhibit growth of human
pancreatic and thyroid cancers in animal models. The IGF/IGF-1R
signaling pathway has also been implicated in protecting tumor
cells from apoptosis induced by a number of cytotoxic agents as
well as molecular targeted therapies including EGFR inhibitors.
Preclinical data also suggest that OSI-906 may be synergistic with
Tarceva in non-small cell lung and pancreatic human tumor
xenografts.
About OSI
Pharmaceuticals
OSI Pharmaceuticals is committed to "shaping medicine and
changing lives" by discovering, developing and commercializing
high-quality, novel and differentiated targeted medicines designed
to extend life and improve the quality of life for patients with
cancer and diabetes/obesity. For additional information about OSI,
please visit http://www.osip.com.
This news release contains forward-looking statements. These
statements are subject to known and unknown risks and uncertainties
that may cause actual future experience and results to differ
materially from the statements made. Factors that might cause such
a difference include, among others, OSI's and its collaborators'
abilities to effectively market and sell Tarceva and to expand the
approved indications for Tarceva, OSI�s ability to protect its
intellectual property rights, safety concerns regarding Tarceva,
competition to Tarceva and OSI�s drug candidates from other
biotechnology and pharmaceutical companies, the completion of
clinical trials, the effects of FDA and other governmental
regulation, including pricing controls, OSI's ability to
successfully develop and commercialize drug candidates, and other
factors described in OSI Pharmaceuticals' filings with the
Securities and Exchange Commission.
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