CytRx announces Phase 2b clinical trial results of aldoxorubicin in subjects with metastatic STS

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.

Updated median PFS at 6 months results are described here:

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.

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.

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.

Source: CytRx Corporation