CytRx Announces Overall Survival Results from Its Global Phase 2b Clinical Trial of Aldoxorubicin in Soft Tissue Sarcoma
Aldoxorubicin Demonstrates 2-Fold Increase in Likelihood of Surviving More than 2 Years versus Doxorubicin and 27% Reduction in the Risk of Death
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LOS ANGELES, Jan. 22, 2015 /PRNewswire/ -- CytRx Corporation (CYTR), a biopharmaceutical research and development company specializing in oncology, today announced encouraging overall survival (OS) results, the secondary endpoint, from its completed 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 OS results in 123 patients demonstrated that aldoxorubicin-treated patients demonstrated a 27 percent reduction in the risk of death compared to patients treated with doxorubicin (HR 0.73: 95% confidence interval 0.44-1.20), the current standard-of-care in this indication. In addition, aldoxorubicin-treated patients demonstrated a 41% likelihood of surviving more than 2 years, a 2-fold increase, compared to a 20% probability for doxorubicin-treated patients. Median overall survival was 16.0 months (95% confidence interval 13.1-not reached) for aldoxorubicin-treated patients versus 14.4 months (95% confidence interval 8.7-20.9) for doxorubicin treated patients (p=0.21). For treatment-naive patients, representing 90% of the patients in the clinical trial, median overall survival was 16.0 months (95% confidence interval 13.1-not reached) for aldoxorubicin-treated patients versus 14.0 months (95% confidence interval 8.7-20.1) for doxorubicin treated patients (p=0.14).
These final OS results were assessed as part of a prospectively planned secondary endpoint analysis and were not powered to demonstrate statistically significant overall survival. The positive trend could be significantly improved, now that the FDA has permitted CytRx to dose aldoxorubicin in all trials until tumor progression. Previously reported primary endpoint results, as determined by both the trial investigators and by blinded central radiology review, found that subjects treated with aldoxorubicin demonstrated highly statistically significantly better clinical outcomes than subjects that received standard doxorubicin therapy for their soft tissue sarcomas. In scans read by trial investigators, progression-free survival (PFS) results demonstrated that treatment with aldoxorubicin increased median PFS approximately 79% to 8.4 months, compared to 4.7 months with doxorubicin, meeting the study's primary endpoint (HR=0.419; p=0.0007). In blinded central radiology review, PFS results demonstrated that treatment with aldoxorubicin increased median PFS approximately 104% to 5.7 months, compared to 2.8 months with doxorubicin, also meeting the study's primary endpoint (HR=0.584; p=0.024).
"The past few decades have brought us very few treatment advances in soft tissue sarcoma," said Sant P. Chawla, M.D., FRACP, Director of the Sarcoma Oncology Center and Principal Investigator of the global Phase 2b clinical trial. "These results indicate that aldoxorubicin could improve clinical outcomes in patients compared to doxorubicin therapy, the current standard-of-care in this indication. We have seen promising improvements in progression-free survival, tumor shrinkage, overall response rates, and now overall survival in patients with a wide variety of soft tissue sarcomas. What is especially meaningful is that after only 6 cycles of aldoxorubicin treatment, the likelihood of survival at 2 years or more is twice that of patients administered doxorubicin. While no drug or combination to date has shown statistically significant increases in median overall survival versus doxorubicin, the improvement in long term outcome for aldoxorubicin-treated patients is an important step forward in offering potential new hope for soft tissue sarcoma patients."
"We are very pleased by these secondary endpoint results, particularly the two-fold increase in the likelihood of survival of more than 2 years, as survival benefit has remained an elusive goal in the treatment of soft tissue sarcoma," said Steven A. Kriegsman, Chairman and CEO of CytRx. "We look forward to the potential of translating these promising results in our pivotal global Phase 3 clinical trial, and to understanding the potential for added benefit when dosing aldoxorubicin until progression, which was not part of the Phase 2b study design."
Other previously reported secondary endpoint results included PFS at 6 months and both complete and partial objective response rates (ORR). In scans read by trial investigators, PFS at 6 months results demonstrated that treatment with aldoxorubicin increased median PFS at 6 months by approximately 86%, compared to doxorubicin, meeting this secondary primary endpoint (p=0.002). In blinded central radiology review, PFS at 6 months results demonstrated that treatment with aldoxorubicin increased median PFS at 6 months by approximately 100%, compared to doxorubicin, meeting this additional secondary endpoint (p=0.02). The ORR as determined by the investigators was 21.7% for aldoxorubicin subjects (2.4% complete response and 19.3% partial response) versus 5.0% for doxorubicin subjects (0% complete response and 5.0% partial response). As assessed by blinded central lab review, 23.8% of aldoxorubicin subjects had a partial response while 0.0% of doxorubicin subjects exhibited any objective response. In addition, a higher percentage of aldoxorubicin-treated subjects demonstrated tumor shrinkage compared to patients treated with doxorubicin, regardless of whether the scans were evaluated by investigators (65.4% vs. 41.2%) or by blinded reviewers (60.8% vs. 39.4%).
Adverse events, as previously reported, 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 cardiotoxicity 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.
Conference Call Information
The call can be accessed by dialing (877) 299-4454 (U.S. and Canada) or (617) 597-5447 (international), and entering passcode 67173895. To access the live webcast, please use either the following link: http://edge.media-server.com/m/p/ae6cd2jy/lan/en or visit the "Events" section of the CytRx website at www.cytrx.com.
The teleconference replay will be available for one week by dialing (888) 286-8010 (U.S. and Canada) or (617) 801-6888 (international). Replay Passcode 57835636 is required for playback. The webcast will also be recorded and available for replay on the company's website for 90 days.
About the Aldoxorubicin Phase 2b Trial Design
In this randomized, open-label, 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.
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.
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 2,000 mg/m2.
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 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, and recently announced that it has received approval from the FDA to continue dosing patients with aldoxorubicin until disease progression in that clinical trial. CytRx is currently evaluating aldoxorubicin in a global Phase 2b clinical trial in small cell lung cancer, a Phase 2 clinical trial in HIV-related Kaposi's sarcoma, a Phase 2 clinical trial in patients with late-stage glioblastoma (brain cancer), a Phase 1b trial in combination with ifosfamide in patients with soft tissue sarcoma, and a Phase 1b trial in combination with gemcitabine in subjects with metastatic solid tumors. 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 clinical trial 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 plans to expand its pipeline of oncology candidates at its laboratory facilities in Freiburg, Germany, based on novel linker technologies that can be utilized with multiple chemotherapeutic agents and may allow for greater concentration of drug at tumor sites. For more information about CytRx Corporation, visit www.cytrx.com.
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 timing or FDA approval of projected commercial sales of aldoxorubicin, 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.
David J. Haen
Vice President, Business Development