Allos Therapeutics, Inc. (NASDAQ: ALTH) today announced the
presentation of further data from the Company’s randomized,
international Phase 2b investigational study of FOLOTYN®
(pralatrexate injection) relative to erlotinib in patients with
Stage IIIB/IV (advanced) non-small cell lung cancer (NSCLC) at the
2010 Chicago Multidisciplinary Symposium in Thoracic Oncology. The
presentation, which includes additional results from several
pre-specified analyses, reinforces the favorable survival data
observed with FOLOTYN in patients with advanced NSCLC—including
outcomes observed in patients with non-squamous and squamous
histologies, as well as results from an analysis adjusting for
important baseline factors and potential imbalances in the number
of patients between cohorts.
“The results presented at this important lung cancer conference
further demonstrate the activity of FOLOTYN relative to erlotinib,
an active comparator, in advanced non-small cell lung cancer –
where nearly all patients progress through initial treatment and
more treatment options are needed,” said Karen Kelly, M.D.,
presenter and an investigator of the study, The University of
Kansas Medical Center. “Based on these results, I believe further
studies are warranted to fully understand the potential role of
FOLOTYN in the treatment of advanced non-small cell lung cancer in
patients with both squamous and non-squamous histologies.”
The objective of this randomized, international, multi-center
Phase 2b study (PDX-012) was to estimate the efficacy of FOLOTYN
relative to that of erlotinib as assessed by overall survival, the
primary endpoint of the trial. As previously reported, patients
receiving FOLOTYN had a 16 percent reduction in the risk of death
compared to erlotinib in the overall (intent-to-treat) population
(n=201; hazard ratio (HR)=0.84) and a 13 percent reduction in the
risk of death in the primary efficacy analysis population (n=166;
HR=0.87). Secondary endpoints included progression-free survival
(PFS) (HR=0.91; median PFS=3.4 months and 2.8 months for FOLOTYN
and erlotinib, respectively). Review of the predefined patient
cohorts indicated that the majority of cohorts responded favorably
to FOLOTYN relative to erlotinib. The largest benefit was observed
in patients with non-squamous cell carcinoma, while comparable
survival was observed across both treatments in patients with
squamous cell carcinoma.
The additional data presented at the Chicago symposium were
based on analyses of the overall population (n=201) and showed that
when adjusting for potential imbalances in several important
baseline factors, the hazard ratio for overall survival, which
favored FOLOTYN, was 0.73. These baseline factors included gender,
race, histology, ECOG performance status, smoking history, response
to prior therapy, prior treatment with pemetrexed, number of prior
regimens, stage of disease at enrollment, weight loss prior to
study and age at study entry. The presentation also included
additional data from patients with non-squamous cell carcinoma
(n=107) and squamous cell carcinoma (n=76). As previously
presented, in patients with non-squamous cell carcinoma, overall
survival and progression-free survival favored FOLOTYN with hazard
ratios of 0.65 and 0.58, respectively; in patients with squamous
cell carcinoma, a hazard ratio of 1.06 for overall survival was
observed. Further details presented at the Chicago symposium showed
that of those patients with non-squamous cell carcinoma who
received FOLOTYN (n=61), 25 percent (n=15) had received prior
treatment with pemetrexed. Additionally, in patients with squamous
cell carcinoma, a hazard ratio of 1.06 was observed for
progression-free survival, which reinforces the potential activity
of FOLOTYN, given that erlotinib has historically shown a benefit
in both overall and progression-free survival relative to placebo
in patients with squamous cell carcinoma.
Of those patients treated with FOLOTYN (n=97) in the trial, 32
patients (33%) discontinued treatment due to adverse events,
including 13 patients who discontinued within the first cycle of
treatment or within 30 days. Of those patients treated with
erlotinib (n=101), 10 patients (10%) discontinued treatment due to
adverse events, including two patients who discontinued within the
first 30 days. The rate of discontinuation for progression of
disease was comparable between the two arms during the first cycle
of treatment. To better understand the impact of discontinuation on
the overall study results, an exploratory landmark analysis was
conducted to assess the activity of FOLOTYN relative to erlotinib
in patients who remained on treatment at 30 days (n=145). These
data showed a hazard ratio of 0.61, which suggests that maintaining
patients on FOLOTYN therapy may be important for efficacy.
The safety profile of FOLOTYN was consistent with that observed
and reported in previous FOLOTYN solid tumor studies. The most
common Grade 3-4 adverse event observed in patients treated with
FOLOTYN was mucositis (23 percent). Other Grade 3-4 adverse events
occurring in more than five percent (but less than 10 percent) of
patients were fatigue (9 percent), dyspnea (6 percent), neutropenia
(6 percent), thrombocytopenia (5 percent) and anemia (5 percent) in
patients treated with FOLOTYN, and rash (8 percent), dyspnea (8
percent), anemia (8 percent) and fatigue (5 percent) in patients
treated with erlotinib.
“We are pleased with these results that demonstrated the
clinical activity of FOLOTYN in patients with advanced non-small
cell lung cancer, an area of high unmet need,” said Charles Morris,
MB ChB, MRCP, chief medical officer at Allos Therapeutics.
The 2010 Chicago Multidisciplinary Symposium in Thoracic
Oncology (December 9-11) is co-sponsored by the American Society of
Clinical Oncology (ASCO), American Society for Radiation Oncology
(ASTRO), International Association for the Study of Lung Cancer
(IASLC), and the University of Chicago. The Company had previously
announced the top-line results from this trial in July and
presented the results for the first time at the European Society of
Medical Oncology in October 2010.
Study Design
The objective of this randomized, open-label, international,
multi-center Phase 2b study was to estimate the efficacy of FOLOTYN
relative to that of erlotinib, marketed as TARCEVA®, as assessed by
overall survival. The trial enrolled 201 current or former smokers
with Stage IIIB/IV (advanced) NSCLC who had received one or two
previous treatments including at least one prior platinum-based
chemotherapy regimen. The primary endpoint of the trial was overall
survival. Secondary endpoints included progression-free survival
and response rate as compared with erlotinib, and the safety and
tolerability of FOLOTYN. The study was not designed to show a
statistically significant difference between the two treatment
arms. No definition of statistical significance was included in the
statistical analysis plan.
The trial – which enrolled patients across 43 locations
worldwide (15 U.S. sites and 28 ex-U.S. sites) – was initiated by
Allos in January 2008 and completed enrollment in July 2009. The
first 35 patients enrolled in the study were randomly assigned
one-to-one to receive FOLOTYN (intravenous push on days 1 and 15 of
a 28-day cycle; initial dose of 230 mg/m2) or erlotinib (oral, 150
mg daily in a 28-day cycle). Following a protocol amendment, 166
patients were randomly assigned one-to-one to receive either
FOLOTYN at 190 mg/m2 or erlotinib at 150 mg/day and then further
stratified by light versus heavy smokers. All patients received
concurrent vitamin therapy of B12 and folic acid. According to the
statistical analysis plan, analyses were also conducted to assess
the activity of FOLOTYN and erlotinib in predefined patient
cohorts, which included light smokers (n=37) and heavy smokers
(n=164), current smokers (n=50) and former smokers (n=151),
squamous (n=76) and non-squamous histology (n=107), and patients
who received prior pemetrexed (n=30) and those who had not
(n=171).
About Lung Cancer
More people die each year from lung cancer than any other type
of cancer – including breast, prostate and colorectal cancers
combined. In 2010, it is estimated that there will be more than
200,000 new cases of lung cancer diagnosed in the United States and
over 150,000 deaths. There are primarily two types of lung cancer:
NSCLC and small cell lung cancer (SCLC). NSCLC accounts for the
majority of lung cancers (about 87 percent) and develops slowly –
often causing few or no symptoms until very late stages. The most
common subtypes of NSCLC are squamous cell carcinoma and
non-squamous carcinomas such as adenocarcinoma and large-cell
undifferentiated carcinoma. Squamous cell carcinomas account for
25-30 percent of all lung cancers while adenocarcinoma and
large-cell undifferentiated carcinoma account for 40 percent and
10-15 percent of lung cancers, respectively. The majority of people
are diagnosed with advanced stage disease and only one to five
percent of people with advanced stage (IIIB/IV) NSCLC survive to
five years. The most widely used therapies to date remain surgery,
chemotherapy, and radiation therapy.
About FOLOTYN
FOLOTYN, a folate analogue metabolic inhibitor, was discovered
by Sloan-Kettering Institute for Cancer Research, SRI International
and Southern Research Institute and developed by Allos
Therapeutics. In September 2009, the U.S. Food and Drug
Administration (FDA) granted accelerated approval for FOLOTYN for
use as a single agent for the treatment of patients with relapsed
or refractory PTCL. This indication is based on overall response
rate. Clinical benefit such as improvement in progression free
survival or overall survival has not been demonstrated. FOLOTYN has
been available to patients in the U.S. since October 2009.
About Allos Therapeutics
Allos is currently focused on the development and
commercialization of FOLOTYN® (pralatrexate injection), a folate
analogue metabolic inhibitor. FOLOTYN is the first and only drug
approved in the U.S. for the treatment of patients with relapsed or
refractory peripheral T-cell lymphoma. Allos is also developing
FOLOTYN in other hematologic malignancies and solid tumors. Allos
retains exclusive worldwide rights to FOLOTYN for all indications.
Allos is headquartered in Westminster, CO. For additional
information, please visit www.allos.com.
IMPORTANT SAFETY INFORMATION
Warnings and Precautions
FOLOTYN may suppress bone marrow function, manifested by
thrombocytopenia, neutropenia, and anemia. Monitor blood counts and
omit or modify dose for hematologic toxicities.
Mucositis may occur. If ≥Grade 2 mucositis is observed, omit or
modify dose. Patients should be instructed to take folic acid and
receive vitamin B12 to potentially reduce treatment-related
hematological toxicity and mucositis.
FOLOTYN can cause fetal harm. Women should avoid becoming
pregnant while being treated with FOLOTYN and pregnant women should
be informed of the potential harm to the fetus.
Use caution and monitor patients when administering FOLOTYN to
patients with moderate to severe renal function impairment.
Elevated liver function test abnormalities may occur and require
monitoring. If liver function test abnormalities are ≥Grade 3, omit
or modify dose.
Dermatologic reactions may occur. Patients with dermatologic
reactions should be monitored closely, and if skin reactions are
severe, FOLOTYN should be withheld or discontinued.
Adverse Reactions
The most common adverse reactions were mucositis (70%),
thrombocytopenia (41%), nausea (40%), and fatigue (36%). The most
common serious adverse events are pyrexia, mucositis, sepsis,
febrile neutropenia, dehydration, dyspnea, and
thrombocytopenia.
Use in Specific Patient Population
Nursing mothers should be advised to discontinue nursing or the
drug, taking into consideration the importance of the drug to the
mother.
Drug Interactions
Co-administration of drugs subject to renal clearance (e.g.,
probenecid, NSAIDs, and trimethoprim/sulfamethoxazole) may result
in delayed renal clearance.
Please see FOLOTYN Full Prescribing Information at
www.FOLOTYN.com.
Safe Harbor Statement
This press release contains forward-looking statements that are
made pursuant to the safe harbor provisions of the Private
Securities Litigation Reform Act of 1995. Such forward-looking
statements include statements regarding the potential safety and
efficacy of FOLOTYN for the treatment of patients with advanced
non-small cell lung cancer, the potential future development of
FOLOTYN for the treatment of advanced non-small cell lung cancer;
and other statements that are other than statements of historical
facts. In some cases, you can identify forward-looking statements
by terminology such as “may,” “will,” “should,” “expects,”
“intends,” “plans,” anticipates,” “believes,” “estimates,”
“predicts,” “projects,” “potential,” “continue,” and other similar
terminology or the negative of these terms, but their absence does
not mean that a particular statement is not forward-looking. Such
forward-looking statements are not guarantees of future performance
and are subject to risks and uncertainties that may cause actual
results to differ materially from those anticipated by the
forward-looking statements. These risks and uncertainties include,
among others: that data from preclinical studies and clinical
trials may not necessarily be indicative of future clinical trial
results; that the safety and/or efficacy profile for FOLOTYN may
not support further clinical development in advanced non-small cell
lung cancer; and the risk that the Company may lack the financial
resources and access to capital to fund future clinical trials for
FOLOTYN. Additional information concerning these and other factors
that may cause actual results to differ materially from those
anticipated in the forward-looking statements is contained in the
"Risk Factors" section of the Company's Quarterly Report on Form
10-Q for the quarter ended September 30, 2010, and in the Company's
other periodic reports and filings with the Securities and Exchange
Commission. The Company cautions investors not to place undue
reliance on the forward-looking statements contained in this press
release. All forward-looking statements are based on information
currently available to the Company on the date hereof, and the
Company undertakes no obligation to revise or update these
forward-looking statements to reflect events or circumstances after
the date of this presentation, except as required by law.
Note: The Allos logo and FOLOTYN name are trademarks of Allos
Therapeutics, Inc.TARCEVA is a registered trademark of OSI
Pharmaceuticals, Inc.
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