May 28, 2014 at 06:00 AM EDT
CytRx Highlights Aldoxorubicin Data from its Global Phase 2b Clinical Trial in First-Line Soft Tissue Sarcoma

CytRx Corporation (Nasdaq: CYTR), a biopharmaceutical research and development company specializing in oncology, today announced updated results from its ongoing multicenter, randomized, open-label global Phase 2b clinical trial investigating the efficacy and safety of aldoxorubicin compared with doxorubicin as first-line therapy in subjects with metastatic, locally advanced or unresectable soft tissue sarcomas (STS). The updated trial results demonstrated that aldoxorubicin significantly increases progression-free survival (PFS), PFS at 6 months, overall response rate (ORR) and tumor shrinkage, compared to doxorubicin, the current standard-of-care, as a first-line treatment in patients with STS. The data trended in favor of aldoxorubicin for all of the major subtypes of soft tissue sarcomas. The results will be presented by Sant P. Chawla, M.D., F.R.A.C.P., Director of the Sarcoma Oncology Center, and principal investigator of the trial, in an oral presentation at the 2014 American Society for Clinical Oncology (ASCO) Annual Meeting, which is taking place May 30–June 3 in Chicago.

“These results indicate that aldoxorubicin is well tolerated and may improve clinical outcomes in patients compared to doxorubicin therapy, the current standard-of-care in this indication,” said Dr. Chawla. “This includes promising improvements in progression-free survival, tumor shrinkage and overall response rates in patients with a wide variety of soft tissue sarcomas. We are hopeful that the next stage of development for aldoxorubicin, a well-tolerated single agent that lacks the cardiotoxicity associated with doxorubicin therapy, will demonstrate its potential to meaningfully extend survival, and will lead to a new treatment option for patients fighting this aggressive, life-threatening cancer.”

“We are delighted that these results were selected for oral presentation at this year’s ASCO meeting,” said Steven A. Kriegsman, CytRx President and Chief Executive Officer. “We look forward to discussing the data with the oncology community and to reporting the full overall survival results from this trial in the second half of 2014. In parallel, we continue to actively enroll patients in our pivotal global Phase 3 trial in second-line STS. In that Phase 3 clinical trial, we are permitted to dose until progression, which could substantially enhance the benefit for sarcoma patients.”

Results in Detail

In this 123-subject, 31-center Phase 2b trial, subjects with advanced soft tissue sarcomas were randomized 2:1 to receive 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 then followed every 6 weeks with CT scans to monitor tumor size. Two approaches were used 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. The primary endpoint was PFS and secondary endpoints included PFS at 6 months for each group, ORR (complete and partial) and overall survival which will be reported when the clinical trial is complete.

Efficacy

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 subjects that received standard doxorubicin therapy for their soft tissue sarcomas. Specifically, both assessments showed an unambiguous 79-104% improvement in PFS among patients treated with aldoxorubicin. Updated median PFS results are described in the table below.

All Subjects

Intent-to-treat

P Value
Scans Read by Investigator
Aldoxorubicin 8.4 months P=0.0004
Doxorubicin 4.7 months
Improvement over dox 3.7 months (79%)
Hazard ratio

0.419 (0.25 - 0.69)

P=0.0007
Scans Read by Blinded Central Lab
Aldoxorubicin 5.7 months P=0.014
Doxorubicin 2.8 months
Improvement over dox 2.9 months (104%)
Hazard ratio

0.584 (0.37 - 0.93)

P=0.024

Updated median PFS at 6 months results are described here:

All Subjects

Intent-to-treat

P Value
Scans Read by Investigator
Aldoxorubicin 68.1% P=0.002
Doxorubicin 36.6%
Improvement over dox 86.1%
Scans Read by Blinded Central Lab
Aldoxorubicin 45.7% P=0.02
Doxorubicin 22.9%
Improvement over dox 99.6%

Updated ORR results are described in the table below. Responses were evaluated using the RECIST 1.1 criteria. Partial responses are defined as at least 30% shrinkage in the target tumors with no increase in non-target tumors or development of new tumors. Complete responses are defined as disappearance of all target lesions.

AldoxorubicinDoxorubicin
Scans Read by Investigator
Complete response 2.4% 0.0%
Partial response 19.3% 5.0%
ORR21.7%5.0%
Scans Read by Blinded Central Lab
Complete response 0.0% 0.0%
Partial response 23.8% 0.0%
ORR23.8%0.0%

The percentage of patients having some shrinkage of their tumors as assessed by RECIST 1.1 criteria is shown below. Regardless of whether the scans were evaluated by investigators or by blinded reviewers, a higher percentage of patients who received aldoxorubicin treatment demonstrated tumor shrinkage compared with patients treated with doxorubicin.

Aldoxorubicin Doxorubicin
Scans Read by Investigator
Tumor Shrinkage (% of subjects) 64.5 41.2
Scans Read by Blinded Review
Tumor Shrinkage (% of subjects) 60.8 39.4

Safety

Adverse events were consistent with known doxorubicin toxicities. The majority of adverse events resolved prior to the following cycle with no treatment discontinuation. Aldoxorubicin-treated subjects experienced a higher percentage of Grade 3 or 4 treatment emergent adverse events (TEAEs) of neutropenia (40% vs. 20%), mucositis (11% vs. 3%) and nausea/vomiting (7% vs. 0%). All TEAEs resolved and were not treatment limiting. No clinically significant cardiac toxicity was seen with aldoxorubicin while approximately 10% of doxorubicin patients had clinically significant cardiotoxicity. Most importantly, there was no clinically significant reduction in cardiac function in the aldoxorubicin patients despite receiving 3.5 times the standard dose of doxorubicin.

ASCO 2014 Oral Presentation Details

Title: “Randomized phase 2b trial comparing first-line treatment with aldoxorubicin versus doxorubicin in patients with advanced soft tissue sarcomas”
Presenter: Sant Chawla, M.D., F.R.A.C.P., Sarcoma Oncology Center
Abstract #: 10502
Date and Time: Sunday, June 1, 2014, 8:24 am – 8:36 am CDT
Session ID: Oral abstract session: Sarcoma

About Soft Tissue Sarcoma

Soft tissue sarcoma 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 soft tissue sarcomas. In 2013 more than 11,400 new cases were diagnosed in the U.S. and approximately 4,400 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

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 450 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.

Aldoxorubicin is currently being studied in a pivotal global Phase 3 clinical trial evaluating the efficacy and safety of aldoxorubicin as a second-line treatment for patients with STS under a Special Protocol Assessment with the FDA. CytRx is also conducting two Phase 2 clinical trials evaluating aldoxorubicin in patients with late-stage glioblastoma (GBM) and HIV-related Kaposi’s sarcoma. Aldoxorubicin has been granted Orphan Drug Designation in the U.S. and Europe for the treatment of soft tissue sarcoma.

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 patients with advanced solid tumors and a Phase 1b pharmacokinetics clinical trial in patients with metastatic solid tumors. CytRx recently initiated, under a special protocol assessment, a pivotal Phase 3 global trial with aldoxorubicin as a therapy for patients with soft tissue sarcomas whose tumors have progressed following treatment with chemotherapy. The Company also recently announced that it has received approval from the FDA to continue dosing patients with aldoxorubicin until disease progression in that clinical trial. CytRx has initiated a Phase 2 clinical trial with aldoxorubicin in patients with late-stage glioblastoma (brain cancer), and 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 any future human testing of aldoxorubicin might not produce results similar to those seen in past human or animal testing, 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, risks related to lawsuits that have been brought against the Company and its officers and/or directors for alleged violations of the securities laws, 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.

Contacts:

Investor Relations:
Argot Partners
Michelle Carroll
212-600-1902
michelle@argotpartners.com
or
Media:
Argot Partners
Eliza Schleifstein
973-361-1546
eliza@argotpartners.com
or
Company Contact:
CytRx Corporation
David J. Haen
Vice President, Business Development
310-826-5648, x304
dhaen@cytrx.com
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