CytRx Initiates Pivotal Global Phase 3 Clinical Trial with Aldoxorubicin

LOS ANGELES--(BUSINESS WIRE)--Mar. 24, 2014-- CytRx Corporation (Nasdaq: CYTR), a biopharmaceutical research and development company specializing in oncology, today announced it has initiated a pivotal global Phase 3 clinical trial to evaluate the efficacy and safety of aldoxorubicin as a second-line treatment for patients with soft tissue sarcoma (STS) under a Special Protocol Assessment with the FDA. 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 (3.5 to 4 times) without several of the major treatment-limiting toxicities seen with administration of doxorubicin alone.

This multicenter, randomized, open-label Phase 3 clinical trial is designed to enroll approximately 400 patients with metastatic, locally advanced or unresectable soft tissue sarcomas who have either not responded to, or have progressed following treatment with, one or more systemic regimens of non-adjuvant chemotherapies. Trial patients will be 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, with up to three comparator regimens to be selected by the investigator at each clinical site. The primary endpoint of the study is progression-free survival (PFS), and secondary endpoints include overall survival, response rates and safety. In January 2014, the Company announced it has received approval from the FDA to amend the Phase 3 protocol to continue dosing patients with aldoxorubicin until disease progression (defined as an increase in the size of measurable tumors by 20% or the development of a new tumor lesion), which creates the potential for substantially improved Phase 3 efficacy results. The Company expects to complete trial enrollment in 2015.

In a phase 1b/2 study, partial responses were observed in 5 of 13 patients with metastatic soft tissue sarcomas who had progressed following initial chemotherapy. Eight of 13 patients showed evidence of tumor shrinkage; 5 of the 8 patients had received prior doxorubicin chemotherapy and had not demonstrated tumor reduction. Updated analysis of median progression-free survival in patients has reached over 17 months without subsequent treatments.

“We have seen few advances in the treatment of soft tissue sarcomas, and only one U.S. regulatory approval, in over two decades,” said Sant Chawla, M.D., Director of the Sarcoma Oncology Center, and principal investigator of the Phase 3 pivotal trial. “Aldoxorubicin has demonstrated highly statistically significant improvements over doxorubicin for STS in multiple outcomes, including PFS, which is extraordinary for a single agent treating these types of tumors. Given aldoxorubicin’s side-effect profile, I believe that it could one day become the treatment of choice for STS, and its potential extends to a wide range of other cancers where anthracyclines are indicated as first- or second-line treatment, including breast, ovarian, multiple myeloma and acute myelocytic leukemia. I, along with my colleagues in the sarcoma community, am excited to participate in this pivotal clinical trial that could unlock aldoxorubicin’s enormous potential.”

"The efficacy data and manageable toxicities observed in our recently completed global Phase 2b trial in first-line STS provide strong rationale for studying aldoxorubicin compared to the standards of care for this extraordinarily difficult to treat cancer," said Steven A. Kriegsman, CytRx President and CEO. "Assuming positive results from this Phase 3 trial, aldoxorubicin has the potential to be a breakthrough for sarcoma patients, providing them with more treatment options beyond standard chemotherapy.”

Following discussions with the FDA, the Phase 3 protocol has been agreed upon under a Special Protocol Assessment (SPA). As part of that assessment, the FDA agreed that the design and planned analysis of the study adequately addresses the objectives necessary to support a regulatory submission for approval.

The clinical trial will be conducted at approximately 100 clinical sites in the U.S., Europe, Canada, Latin America, Asia Pacific and Australia.

Aldoxorubicin Development Rationale and Strategy

Aldoxorubicin has been tested in over 200 patients with cancer. CytRx recently reported highly statistically significant positive results from a global, multicenter Phase 2b clinical trial evaluating aldoxorubicin compared to doxorubicin as a first-line therapy in 123 patients with advanced soft tissue sarcoma. 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.

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.

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. Collectively, these data contribute to the rationale for initiating the pivotal Phase 3 study.

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.

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 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 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, including the global Phase 3 clinical trial described in this press release, 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, 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.

Source: CytRx Corporation

Posted: March 2014

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