CytRx initiates Phase 3 clinical trial to evaluate efficacy of aldoxorubicin in STS patients

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>

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.

Source: CytRx Corporation