CytRx
Corporation (NASDAQ: CYTR), a biopharmaceutical research and
development company specializing in oncology, today announced highly
positive top-line efficacy results from a multicenter, randomized,
open-label global Phase 2b clinical trial. The trial investigated the
efficacy and safety of aldoxorubicin compared with doxorubicin in
subjects with first-line metastatic, locally advanced or unresectable
soft tissue sarcomas (STS). Aldoxorubicin combines the chemotherapeutic
agent doxorubicin with a novel linker-molecule that binds specifically
to albumin in the blood to allow for delivery of higher amounts of
doxorubicin (3½ to 4 times) without the major dose-limiting toxicities
seen with administration of doxorubicin alone.
In this 123-subject, 31-center global Phase 2b clinical trial, subjects
with advanced soft tissue sarcomas were administered either 350 mg/m2
of aldoxorubicin (83 subjects) or 75 mg/m2 of doxorubicin (40
subjects) every 3 weeks for up to 6 cycles. Subjects were followed every
6 weeks with CT scans to monitor tumor size. The primary endpoint was
progression-free survival (PFS) as determined by both investigators at
study sites and by a blinded radiology review performed at an
independent central laboratory. Secondary endpoints included overall
response rates (complete and partial) and PFS at 6 months for each
group, and overall survival which will be reported when the clinical
trial is complete.
Consistent with the trial protocol, CytRx used two approaches to
evaluate the efficacy of aldoxorubicin compared to doxorubicin in
patients with soft tissue sarcomas: assessment by the study
investigators, as well as assessment by a blinded central laboratory
review. In this study, both investigator assessment and central lab
review showed an unambiguous 80-100% improvement in PFS among patients
treated with aldoxorubicin. In an intent-to-treat analysis, the
investigator-assessed median PFS was 8.4 months for aldoxorubicin
patients versus 4.7 months for doxorubicin patients (p=0.0002), while
the blinded central lab review indicated that median PFS for
aldoxorubicin patients was 5.7 months versus 2.8 months for doxorubicin
patients (p=0.018). Per investigators, 67.1% of aldoxorubicin patients
had not progressed at 6 months, compared with 36.1% of
doxorubicin-treated patients (p=0.005). By blinded central lab review,
46.8% of aldoxorubicin patients had not progressed at 6 months, compared
with 23.7% of doxorubicin patients (p=0.038).
The overall response rate as determined by the investigators was 25.4%
for aldoxorubicin subjects (2.7% complete response and 22.7% partial
response) versus 5.4% for doxorubicin subjects (0% complete response and
5.4% partial response). As assessed by blinded central lab review, 23.0%
of aldoxorubicin subjects had a partial response while 0.0% of
doxorubicin subjects exhibited any objective response.
As determined by both the trial investigators and by blinded central
radiology review, subjects treated with aldoxorubicin demonstrated
highly statistically significant better clinical outcomes than those
receiving standard doxorubicin therapy for their soft tissue sarcomas.
”These results are extraordinary for a single agent treating these
chemotherapy-resistant tumors,” said study principal investigator Sant
Chawla, M.D. of the Sarcoma Oncology Center in Santa Monica, California.
“Aldoxorubicin is the first and only single agent to surpass doxorubicin
as a first-line treatment for soft tissue sarcomas.”
Dr. Chawla added, “Previous results from this trial presented at the
Connective Tissue Oncology Meeting in October indicated that subjects
treated with aldoxorubicin demonstrated no significant cardiotoxicity
whereas doxorubicin shows cardiotoxicity at certain cumulative dose
levels. No subjects left the study due to aldoxorubicin side effects.
These findings together suggest that aldoxorubicin could become the
treatment of choice for soft tissue sarcomas. Yet this drug’s potential
extends much further because doxorubicin in particular and
anthracyclines in general are indicated as first- or second-line therapy
for many other common cancers including breast, ovarian, small-cell
lung, multiple myeloma, acute myelocytic leukemia and more. As such, the
ability of aldoxorubicin to safely administer high doses of doxorubicin
holds tremendous therapeutic potential to oncologists and their patients
worldwide.”
CytRx President and CEO Steven A. Kriegsman commented, “Aldoxorubicin is
a major advance for treating soft tissue sarcomas. We extend gratitude
to the investigators who so adeptly managed the conduct of this trial
and to the patients and their families who participated in it. These
data prove that by applying our proprietary linker technology to target
the release of doxorubicin directly at the site of cancer we are able to
safely increase the dosage of doxorubicin by approximately three and
one-half to four times with tremendous clinical benefit to the patient.”
In the Phase 2b clinical trial aldoxorubicin was found to be safe and
well tolerated. All adverse events in subjects treated with
aldoxorubicin were consistent with the known side effects of
doxorubicin, resolved before the administration of the next dose and did
not require treatment discontinuation. There were no treatment-related
deaths in the aldoxorubicin group.
About the Phase 2b Trial Design
The study examined 123 subjects who received either aldoxorubicin or
doxorubicin in a 2:1 randomization, respectively. Aldoxorubicin was
administered to 83 subjects at a dosage of 350 mg/m2
(doxorubicin equivalents of 260 mg/m2) as a 30-minute
intravenous infusion on Day 1 of each cycle, while doxorubicin (75 mg/m2)
was administered to 40 subjects as a 5-30 minute infusion on Day 1 of
each cycle. A cycle of therapy was defined as a 3-week (21-day) period.
Multiple cycles were administered until the subject was withdrawn from
therapy or until a maximum of 6 cycles were administered. CT scans were
obtained every 6 weeks to assess tumor response and progression, and
adverse events were collected in a case report form.
About Soft Tissue Sarcoma
STS is a cancer occurring in muscle, fat, blood vessels, tendons,
fibrous tissues and connective tissue, and can arise anywhere in the
body at any age. According to the American Cancer Society, there are
approximately 50 types of STS; and in 2013 more than 11,400 new cases
will be diagnosed in the U.S., and approximately 4,400 Americans will
die from STS. 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
The widely used chemotherapeutic agent 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 500 mg/m2. Aldoxorubicin
combines doxorubicin with a novel single-molecule linker that binds
directly and specifically to circulating albumin, the most plentiful
protein in the bloodstream. Protein-hungry tumors concentrate albumin,
thus increasing 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.
This allows for greater doses (3 ½ to 4 times) of doxorubicin to be
administered while reducing its toxic side effects. In studies thus far
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 g/m2.
Conference Call and Webcast
CytRx management will be hosting a conference call and webcast today
beginning at 10:30 a.m. Eastern time. To access the conference call,
dial 888-463-4383 (U.S. and Canada) or 706-679-5355 (international
callers). 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: 19821609.
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 (formerly known as INNO-206), its
improved version of the widely used chemotherapeutic agent doxorubicin.
CytRx has completed a global Phase 2b clinical trial with aldoxorubicin
as a first-line therapy for soft tissue sarcomas, a Phase 1b/2 clinical
trial primarily in the same indication, a Phase 1b study of
aldoxorubicin in combination with doxorubicin in subjects with advanced
solid tumors and a Phase 1b pharmacokinetics clinical trial in subjects
with metastatic solid tumors. CytRx plans to initiate under a special
protocol assessment a potential pivotal Phase 3 global trial with
aldoxorubicin as a therapy for subjects with soft tissue sarcomas whose
tumors have progressed following treatment with chemotherapy. CytRx has
initiated a Phase 2 clinical trial with aldoxorubicin in subjects with
late-stage glioblastoma (brain cancer), and plans to initiate a Phase 2
clinical trial in HIV-related Kaposi’s sarcoma. CytRx plans to expand
its pipeline of oncology candidates based on a linker platform
technology that can be utilized with multiple chemotherapeutic agents
and may allow for greater concentration of drug at tumor sites. CytRx
also has rights to two additional drug candidates, tamibarotene and
bafetinib. CytRx completed its evaluation of bafetinib in the ENABLE
Phase 2 clinical trial in high-risk B-cell chronic lymphocytic leukemia
(B-CLL), and plans to seek a partner for further development of
bafetinib. For more information about CytRx Corporation, visit www.cytrx.com.
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 outcome, timing and results of CytRx's clinical trials,
the risk that the results of any future human testing of aldoxorubicin,
including the final data from the Phase 2b clinical testing of
aldoxorubicin as a first-line treatment in patients with metastatic,
locally advanced or unresectable soft tissue sarcomas who have not been
previously treated with any chemotherapy, might not produce objective
response or safety results similar to the data described in this press
release, risks related to CytRx's ability to manufacture its drug
candidates in a timely fashion, cost-effectively or in commercial
quantities in compliance with stringent regulatory requirements, risks
related to CytRx's need for additional capital or strategic partnerships
to fund its ongoing working capital needs and development efforts,
including the Phase 3 clinical development of aldoxorubicin, and the
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.
Copyright Business Wire 2013