LOS ANGELES, Nov. 29, 2016 /PRNewswire/ -- CytRx
Corporation (NASDAQ: CYTR) today announced positive updated results
from its pivotal Phase 3 clinical trial evaluating aldoxorubicin
compared to investigator's choice in patients with relapsed or
refractory soft tissue sarcomas (STS). The study, which
enrolled 433 patients, demonstrated a statistically significant
improvement in progression-free survival (PFS) between
aldoxorubicin and investigator's choice therapy in 246 patients
with leiomyosarcoma and liposarcoma, (p=0.007). The hazard
ratio (HR) was 0.62 (95% CI 0.44-0.88), representing a 38%
reduction in the risk of tumor progression for patients receiving
aldoxorubicin versus investigator's choice. Leiomyosarcoma
and liposarcoma are the two most common types of STS and accounted
for 57% of the patients enrolled in the trial.
Aldoxorubicin demonstrated a statistically significant
improvement in PFS over investigator's choice in 312 patients
treated in North America (p=0.028;
HR=0.71, 95% CI 0.53-0.97). Notably, aldoxorubicin performed
better than investigator's choice for the entire study population
and narrowly missed statistical significance (p=0.12; HR=0.81, 95%
CI 0.64-1.06). All responses were determined by an
independent, blinded central lab assessment of scans.
"This data represents a major step forward for STS, a rare,
highly complex and very difficult-to-treat group of cancers,"
commented Sant Chawla, M.D.,
F.R.A.C.P., Director of the Sarcoma Oncology Center in Santa Monica, California, and Principal
Investigator for the Phase 3 trial. "These results are
important because they demonstrate that treatment with
aldoxorubicin can extend the time to progression in a clinically
meaningful way. The trial design used was more stringent than
any prior clinical trial in STS as it compared aldoxorubicin to
real world alternatives. The control arm allowed trial
investigators to select any one of the five most widely used
treatments best suited for their patients' specific type of
STS. Unlike other clinical trials for relapsed or refractory
STS which used either dacarbazine or placebo as the control, this
study was biased in favor of choosing the best therapy for the
patients, a truly unique study design."
CytRx plans to submit the results of this clinical trial for
presentation at an upcoming major scientific meeting.
In the entire study population, aldoxorubicin achieved a
statistically significant improvement in the disease control rate
(DCR; defined as objective response rate (ORR) plus stable disease
for at least 4 months) of 29.4% versus 20.5% for the patients
treated with investigator's choice (p=0.030). In North
American patients, the benefit was even more pronounced with
aldoxorubicin-treated patients exhibiting a DCR of 32.9%, compared
to 19.2% for patients treated with investigator's choice (p=0.007),
an overall improvement of 71%. ORR in North American patients
also favored aldoxorubicin over investigator's choice, 8.7% versus
3.3% (p=0.058). Of note, no objective responses were observed
in patients treated with Votrient® (pazopanib). Patients
continue to be followed for overall survival (OS), a secondary
endpoint, and CytRx expects the OS data to be available in
2017.
PFS, DCR and ORR data are summarized in the following table:
Phase 3
Aldoxorubicin Efficacy Results
|
|
N
|
Aldoxorubicin
|
Investigator's
Choice
|
P
Value
|
All patients with
Leiomyosarcoma and Liposarcoma
(PFS)
|
246
|
HR = 0.62 (95% CI
0.44-0.88)
|
0.007
|
|
|
|
|
North
American1 patients (PFS)
|
312
|
HR = 0.71 (95% CI
0.53-0.97)
|
0.028
|
Disease Control Rate
(DCR)2
|
32.9%
|
19.2%
|
0.007
|
Objective Response
Rate (ORR)
|
8.7%
|
3.3%
|
0.058
|
All patients
(PFS)
|
433
|
HR = 0.81 (95%
CI 0.64-1.06)
|
0.120
|
Disease Control Rate
(DCR)2
|
29.4%
|
20.5%
|
0.030
|
|
|
|
|
|
|
1Per trial
statistical analysis plan, North America is defined as United
States, Canada and Australia and comprises 72% of total trial
patients
|
2DCR=ORR +
stable disease for ≥4 months
|
Pre-specified analyses were based on sarcoma histopathology and
geography. The geographic analysis includes patients from
North America (defined as
the United States, Canada and Australia, per the trial statistical analysis
plan). The 312 patients treated in North America comprise 72% of the total trial
population, including 296 patients from the United States, 8 patients from
Canada and 8 patients from
Australia. The 246 patients with leiomyosarcoma or
liposarcoma comprise 57% of the total trial population.
Aldoxorubicin did not cause clinically significant cardiac,
renal, or hepatic toxicities. For the global trial
population, the most commonly reported adverse events were
neutropenia and anemia consistent with prior clinical trials with
aldoxorubicin. Grade 3 or higher hypertension occurred in patients
receiving Votrient® (pazopanib). Grade 3 or higher adverse
events were manageable with supportive care and occurred at a rate
of 61% for patients receiving aldoxorubicin and 46% in patients
treated with investigator's choice. Importantly,
treatment-emergent adverse events leading to discontinuation
occurred in 4.2% of patients treated with aldoxorubicin, compared
to 6.3% for patients receiving investigator's choice. Serious
adverse events, primarily febrile neutropenia that resolved and
rarely led to treatment termination occurred more frequently in
patients administered aldoxorubicin. Treatment-related deaths
occurred in one aldoxorubicin-treated patient and in no patients
receiving investigators' choice drugs.
Based on these results, CytRx expects to submit a New Drug
Application (NDA) with the U.S. Food and Drug Administration (FDA)
for aldoxorubicin as a treatment for patients with relapsed or
refractory STS in 2017.
"These results show that globally leiomyosarcoma and liposarcoma
patients treated with aldoxorubicin exhibited significantly longer
PFS than patients treated with both FDA-approved and commonly used
therapies in the second-line setting," said Daniel Levitt, M.D., Ph.D., EVP and Chief
Medical Officer of CytRx. "We are also very encouraged by the
statistically significant improvements observed in North American
STS patients treated with aldoxorubicin who exhibited both longer
PFS and superior response rates."
"We are deeply grateful for the support and commitment of the
sarcoma investigators, along with the patients and families who
took part in or contributed to this Phase 3 trial," stated
Steven A. Kriegsman, CytRx's
Chairman and Chief Executive Officer. "We look forward to
sharing the data from these key patient populations with the FDA to
support an NDA for aldoxorubicin as a second-line treatment for
patients suffering with soft tissue sarcomas."
Conference Call and Webcast
CytRx management will be hosting a conference call and webcast
today beginning at 8:30 a.m. Eastern
Time / 5:30 a.m. Pacific Time
to discuss the results of the Phase 3 trial. To access the
conference call, dial 844-358-6753 (U.S. and Canada) or 216-562-0397 (international
callers) and enter the conference ID number: 27115631. A
webcast will be available in the investor relations section of the
company's website, www.cytrx.com. A replay of the call and
webcast will begin approximately two hours after the live call has
ended. To access the replay, dial 855-859-2056 (U.S. and
Canada) or 404-537-3406
(international callers) and enter the conference ID number:
27115631.
About the Phase 3 Clinical Trial
The randomized, controlled Phase 3 trial enrolled a total of 433
patients at 79 clinical sites. Patients with metastatic,
locally advanced or unresectable soft tissue sarcomas who had
either not responded to, or who had progressed following treatment
with one or more systemic regimens of non-adjuvant chemotherapy
were randomized 1:1 to be treated with aldoxorubicin or the
investigator's choice of an approved chemotherapeutic regimen,
including doxorubicin, ifosfamide, dacarbazine, pazopanib
(Votrient®), or gemcitabine plus docetaxel. The primary
endpoint of the study is PFS. Secondary endpoints include
overall survival, response rates, disease control rates and
safety.
About Soft Tissue Sarcoma
Soft tissue sarcoma is a cancer occurring in muscle, fat, blood
vessels, tendons, fibrous tissues and connective tissue. It
can arise anywhere in the body at any age. STS remains a high
unmet medical need because of the difficulty in treating the more
than 50 types of this aggressive cancer. According to the
American Cancer Society, in 2016 more than 12,300 new cases were
diagnosed in the U.S. and approximately 5,000 Americans died from
this disease. In addition, approximately 40,000 new cases and
13,000 deaths in the U.S. and Europe are part of a growing underserved
market.
About Aldoxorubicin
Aldoxorubicin is a rationally-engineered cytotoxic which
combines doxorubicin, a widely used chemotherapeutic agent, with a
novel linker molecule that binds directly and specifically to
circulating albumin, the most abundant protein in the
bloodstream. Protein-hungry tumors concentrate albumin, which
facilitates the delivery of the linker molecule with the attached
doxorubicin to tumor sites. In the acidic environment of the
tumor, but not the neutral environment of healthy tissues,
doxorubicin is released. Typically, doxorubicin is delivered
systemically and is highly toxic, which limits its dose to a level
below its maximum therapeutic benefit. Doxorubicin also is
associated with many side effects, especially the potential for
damage to heart muscle at cumulative doses greater than 450 mg/m2.
Using this acid-sensitive linker technology, aldoxorubicin delivers
greater doses of doxorubicin (3 ½ to 4 times). To date, there has
been no evidence of clinically significant effects of aldoxorubicin
on heart muscle, even at cumulative doses of drug well in excess of
2,000 mg/m2. Aldoxorubicin is the first-ever single agent to show
superiority over doxorubicin in a randomized clinical trial in
first-line STS.
About CytRx Corporation
CytRx Corporation is a biopharmaceutical research and
development company specializing in oncology. CytRx currently is
focused on the clinical development of aldoxorubicin, its improved
version of the widely used chemotherapeutic agent
doxorubicin. CytRx is also expanding its pipeline of oncology
candidates at its laboratory facilities in Freiburg, Germany, through its LADR™ (Linker Activated
Drug Release) technology platform, a discovery engine designed to
leverage CytRx's expertise in albumin biology and linker technology
for the development of a new class of anti-cancer therapies.
Forward-Looking Statements
This press release contains forward-looking statements within
the meaning of Section 21E of the Securities Exchange Act of 1934,
as amended. Such statements involve risks and uncertainties that
could cause actual events or results to differ materially from the
events or results described in the forward-looking statements,
including risks relating to the timing and final results of CytRx's
clinical testing of aldoxorubicin, timing of CytRx's preparation
and submission of an NDA for aldoxorubicin for the treatment of STS
and FDA acceptance and review of any NDA, the risk that CytRx may
be unsuccessful in obtaining FDA approval or, if approval is
obtained, in commercializing aldoxorubicin in the United States or elsewhere, risks related
to CytRx's need for additional capital or strategic partnerships to
fund its ongoing working capital needs and other risks and
uncertainties described in the most recent annual and quarterly
reports filed by CytRx with the Securities and Exchange Commission
and current reports filed since the date of CytRx's most recent
annual report. All forward-looking statements are based upon
information available to CytRx on the date the statements are first
published. CytRx undertakes no obligation to publicly update or
revise any forward-looking statements, whether as a result of new
information, future events or otherwise.
Company Contact:
CytRx Corporation
David J. Haen
Vice President, Business Development and Investor Relations
(310) 826-5648, ext. 304
dhaen@cytrx.com
Media Contact:
Argot Partners
Eliza Schleifstein
(973) 361-1546
eliza@argotpartners.com
Investor Relations Contact:
Argot Partners
Michelle Carroll
(212) 600-1902
michelle@argotpartners.com
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SOURCE CytRx Corporation