Allos Therapeutics, Inc. (NASDAQ: ALTH) today reported new
analyses of data from the Company's pivotal PROPEL trial of
FOLOTYN® (pralatrexate injection) in patients with relapsed or
refractory peripheral T-cell lymphoma (PTCL) at the 52nd American
Society of Hematology (ASH) Annual Meeting held in Orlando,
Florida.
Results from three new retrospective analyses of single-agent
FOLOTYN showed:
- Of the patients who received prior
‘ICE’ or similar aggressive combinations (primarily used for
salvage treatment of PTCL) (n=20), objective responses were
observed in eight patients (40%) treated with FOLOTYN as assessed
by independent central review. These results indicate activity of
FOLOTYN in patients with relapsed or refractory PTCL who received
prior ICE-based chemotherapy.
- Of the patients whose disease
progressed following treatment with first-line ‘CHOP’ therapy
(n=15), objective responses were observed in seven patients (47%)
treated with FOLOTYN as assessed by independent central review.
These results indicate activity of FOLOTYN in the second-line
treatment setting following CHOP for patients with relapsed or
refractory PTCL.
- Of the patients who received three or
more systemic therapies prior to enrolling in the PROPEL trial
(n=57), objective responses and progression-free survival decreased
with each line of therapy prior to FOLOTYN. Following treatment
with FOLOTYN, responses and progression-free survival increased
relative to the immediate prior line of therapy, thus reversing the
trend of progressive resistance.
“These analyses demonstrate the ability of FOLOTYN to achieve
responses in patients in the second-line treatment setting
immediately following treatment with CHOP, and indicate that
FOLOTYN may be an effective treatment option in patients who have
progressed after aggressive chemotherapy regimens such as ICE,”
said Owen A. O’Connor, M.D., Ph.D., principal investigator in the
PROPEL study; deputy director for Clinical Research and Cancer
Treatment, NYU Cancer Institute; chief, Division of Hematologic
Malignancies and Medical Oncology; professor of Medicine and
Pharmacology at the NYU Langone Medical Center. “These analyses
also suggest that FOLOTYN may reverse the pattern of progressive
resistance in patients with drug-resistant peripheral T-cell
lymphoma.”
“Allos is pleased that PROPEL has and continues to provide
important insights into the role of FOLOTYN to treat patients with
relapsed or refractory peripheral T-cell lymphoma – which is a
devastating disease,” said Charles Morris, MB ChB, MRCP, chief
medical officer at Allos Therapeutics.
Below is a summary of conclusions and key findings from the new
analyses of data from the pivotal PROPEL trial – which enrolled 115
patients, 109 of whom were considered evaluable for efficacy
according to the trial protocol. Study endpoints included overall
response rate (ORR) – defined as complete response, unconfirmed
complete response, and partial response – as well as duration of
response (DoR), progression-free survival (PFS), and overall
survival (OS). ORR, DoR and PFS were evaluated by independent
central review using International Workshop Criteria (IWC).
Poster #1753: Pralatrexate is Effective in Patients with
Relapsed/Refractory Peripheral T-cell Lymphoma (PTCL) After
Progression Following Prior Ifosfamide, Carboplatin, and Etoposide
(ICE)-based Regimens
A poster presentation by Dr. Andre Goy of The John Theurer
Cancer Center at Hackensack University Medical Center assessed the
efficacy of FOLOTYN in patients with PTCL whose disease progressed
following prior treatment with an ICE-based regimen (n=20). Results
of this analysis indicate activity of FOLOTYN in patients with
relapsed or refractory PTCL who received prior ICE-based
chemotherapy.
Prior to enrolling in PROPEL, response to ICE-based therapy was
observed in five of 20 patients (25%). Of those patients whose
disease progressed following prior ICE-based chemotherapy,
objective responses with FOLOTYN were observed in eight of 20
patients (40%), including several patients who did not respond to
ICE-based therapy; these results were consistent across independent
central review and local investigator review. Three of the 20
patients (15%), based on independent central review, and five of
the 20 patients (25%), based on local investigator review,
experienced complete response; two patients went on to receive a
stem cell transplant, which may result in long-term remissions in
some patients. The median duration of response to FOLOTYN was 13.1
months per independent central review and 16.2 per local
investigator review. The safety profile observed in these patients
was consistent with that observed in the overall PROPEL study. The
most common non-hematologic Grade 3-4 adverse event observed in
these patients was mucositis (30%); the most common hematologic
Grade 3-4 adverse events were anemia (45%) and thrombocytopenia
(40%).
Abstract #4882: Pralatrexate is Effective as Second-line
Treatment Following
Cyclophosphamide/Doxorubicin/Vincristine/Prednisone (CHOP) Failure
in Patients with Relapsed or Refractory Peripheral T-cell Lymphoma
(PTCL)
This analysis by Dr. Andrei Shustov of Seattle Cancer Care
assessed the efficacy of FOLOTYN as a second-line treatment in
patients with PTCL whose disease progressed following first-line
treatment with CHOP. Although CHOP is the most common therapy for
first-line treatment of PTCL, most patients progress within 6 to 12
months and there is no standard of care for second-line treatment.
Results of this analysis indicate activity of FOLOTYN in the
second-line treatment setting following CHOP for patients with
relapsed or refractory PTCL.
Of the 15 evaluable patients in the PROPEL study whose disease
progressed following first-line treatment with CHOP, objective
responses with FOLOTYN were observed in seven patients (47%) as
assessed by independent central review and in six patients (40%) as
assessed by local investigators. Three of the 15 patients (20%),
based on independent central review, and four of the 15 patients
(27%), based on local investigator review, experienced a complete
response; two of these patients went on to receive a stem cell
transplant and sustain complete responses for 20.1 and 21.7 months.
The median duration of response to FOLOTYN was 12.5 months per
local investigator review; by independent central review, the
median duration of response had not yet been reached.
Abstract #4881: Pralatrexate Reverses the Trend to
Progressive Resistance to Successive Systemic Treatment Regimens in
Patients with Relapsed/Refractory Peripheral T-Cell Lymphoma
(PTCL)
This analysis by Dr. Owen O’Connor of the NYU Langone Medical
Center was conducted to determine whether a trend of progressive
resistance is observed in patients with relapsed or refractory
PTCL, as well as to assess the potential ability of FOLOTYN to
overcome drug resistance. Progressive resistance – characterized by
a continual decrease of responses and progression-free survival in
patients in the second-line treatment setting and then with each
subsequent therapy – is often observed in hematologic malignancies
and solid tumors. Results of this analysis demonstrated, for the
first time, that patients with PTCL exhibit the same pattern of
progressive drug resistance observed in other tumor types. This
analysis also showed that following treatment with FOLOTYN,
response rates and progression-free survival increased relative to
the immediate prior line of therapy, thus reversing the trend of
progressive resistance.
Of the 57 patients who received three lines of therapy or more
prior to enrolling in the PROPEL trial, objective responses and
progression-free survival decreased with each line of treatment –
with response rates decreasing from 56 percent (32 of 57 patients)
to 30 percent (17 of 57 patients) and progression-free survival
decreasing from 213 days to 95 days. Following treatment with
FOLOTYN, response rates and progression-free survival increased to
40 percent (23 of 57 patients) and 134 days, respectively.
As principal investigator of the PROPEL study, Dr. O’Connor
receives research funding for studies of FOLOTYN from Allos
Therapeutics.
About PROPEL
PROPEL (Pralatrexate in Patients with Relapsed
or Refractory Peripheral T-Cell Lymphoma), an
open-label, single-arm, multicenter, international Phase 2 clinical
trial, enrolled 115 patients with relapsed or refractory PTCL, 109
of whom were considered evaluable for efficacy according to the
trial protocol. Patients were considered evaluable if they received
at least one dose of FOLOTYN, their diagnosis of PTCL was confirmed
by independent pathology review, and they had relapsed or
refractory disease after at least one prior treatment. Patients
were treated with FOLOTYN at 30 mg/m2 once weekly by IV push over
3-5 minutes for 6 weeks in 7-week cycles until disease progression
or unacceptable toxicity. In addition, patients received 1mg of
vitamin B12 intramuscularly every 8-10 weeks and 1.0-1.25 mg of
folic acid orally on a daily basis.
The primary efficacy endpoint was overall response rate (ORR) –
defined as complete response (CR), unconfirmed complete responses
(CRu), and partial response (PR) – as assessed by International
Workshop Criteria (IWC). The key secondary efficacy endpoint was
duration of response. Response assessments were scheduled at the
end of cycle 1 and then every other cycle (every 14 weeks).
Duration of response was measured from the first day of documented
response to disease progression or death. Response and disease
progression were evaluated by independent central review using the
IWC.
About Peripheral T-Cell Lymphoma
T-cell lymphomas comprise a biologically diverse group of blood
cancers that account for approximately 10% to 15% of all cases of
non-Hodgkin lymphoma (NHL) in the United States.1-3 The American
Cancer Society estimated that approximately 66,000 new cases of NHL
were expected to be diagnosed in the U.S. in 2010. The Company
estimates the current annual incidence of PTCL in the U.S. to be
approximately 5,900 patients. The outcome of patients with PTCL is
poor and the majority of patients ultimately have refractory
disease to a variety of agents, including multi-agent chemotherapy
with CHOP (cyclophosphamide, doxorubicin, vincristine, and
prednisone) or CHOP-like regimens. The 5-year overall survival rate
in these patients is 25% to 40%, depending on sub-type.4-5
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 Therapeutics, Inc. (NASDAQ: ALTH) is a biopharmaceutical
company committed to the development and commercialization of
innovative anti-cancer 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 future
development of FOLOTYN for the treatment of patients with T-cell
lymphoma or any other type of 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 patients with T-cell lymphoma or any other type of
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.
References:
1.
Savage KJ. Peripheral T-cell Lymphomas.
Blood Rev. 2007; 21:201-216.
2.
Hennessy BT, Hanrahan EO, Daly PA.
Non-Hodgkin lymphoma: an update [review]. Lancet Oncol.
2004;5(6):341-353.
3.
O'Leary HM, Savage KJ. Novel therapies in
peripheral T-cell lymphomas [review]. Curr Oncol Rep.
2008;134(5):202-207.
4.
Savage KJ, Chhanabhai M, Gascoyne RD, et
al. Characterization of peripheral T-cell lymphomas in a single
North American institution by the WHO classification. Ann Oncol
2004;15(10):1467-75.
5.
The Non-Hodgkin's Lymphoma Classification
Project. A clinical evaluation of the International Lymphoma Study
Group classification of non-Hodgkin's lymphoma. Blood.
1997;89(11):3909-3908.
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