Aldoxorubicin Demonstrates Benefit in Phase IIb Trial in Soft Tissue Sarcomas

Source: The Web site of the National Cancer Institute (http://www.cancer.gov)

Soft Tissue Sarcoma

Source: Dr. Timothy Triche, The Web site of the National Cancer Institute (http://www.cancer.gov)

Aldoxorubicin demonstrated response rates that culminated in a higher incidence of stable disease versus doxorubicin as a first-line treatment for advanced soft tissue sarcomas, according to results from an ongoing phase IIb study.

In the study, patients treated with aldoxorubicin had an overall response rate of 22% compared with 0% in those treated with doxorubicin (P= .004). Additionally, 50% of those treated with doxorubicin had progressive disease compared to 32% of patients treated with aldoxorubicin. CytRx Corporation, the company developing the drug, released interim results from the study in a poster at the 18th Annual Connective Tissue Oncology Society Meeting.

“We are very pleased with the continued clinical findings from our global phase IIb trial with aldoxorubicin as a first-line treatment in advanced soft tissue sarcomas, and the strength of the data presented today reinforces our belief that the linker technology platform can be applied to a broad range of cancer treatments,” said CytRx President and CEO Steven A. Kriegsman, in a statement.

Aldoxorubicin is a combination of doxorubicin and a novel single-molecule linker that quickly binds directly to endogenous circulating albumin through the EMCH linker. Protein-hungry tumors concentrate albumin, which increases the delivery of the linker molecule (with attached doxorubicin) to tumor sites. Doxorubicin is then released in the acidic environment of the tumor, leaving the neutral environment of healthy tissues unaffected. This proposed mechanism of action allows for greater doses of doxorubicin to be administered in a greater number of drug cycles while reducing toxic side effects.

In this phase IIb trial, 123 patients age 18-80 years with metastatic, locally advanced, or unresectable soft tissue sarcomas were randomized 2:1 to receive 350 mg/m²aldoxorubicin (260 mg/m²doxorubicin equivalents) intravenously (n = 36) or 75 mg/m²doxorubicin intravenously every 3 weeks for up to 6 cycles (n = 11).

The findings indicate that aldoxorubicin can be safely administered at doses exceeding 3.5 times the standard dosing of doxorubicin. A higher percentage of patients treated with aldoxorubicin completed both 4 cycles and 6 cycles of treatment compared with those receiving doxorubicin. There was no significant reduction in cardiac function reported in the aldoxorubicin population.

Twenty-four serious adverse events (SAEs) were associated with aldoxorubicin versus 6 SAEs associated with doxorubicin. All SAEs were resolved and treatment was not discontinued. One treatment-related death in a patient treated with doxorubicin was seen.

In an earlier phase I study, aldoxorubicin demonstrated safety and clinical responses in patients with sarcoma, breast, and lung cancers. Doses in this study were administered at up to 4x the standard dosing of doxorubicin without an increase in observed side effects.

In a phase Ib/II trial, 76.9% (10/13) of evaluable patients with relapsed or refractory soft tissue sarcoma saw clinical benefit with aldoxorubicin at the maximum tolerated dose. Of the 13 evaluable patients, 5 achieved partial response, 7 showed prolonged stable disease, and 8 had tumor shrinkage. In the trial, median estimated PFS was 6.4 months, which compares favorably with the historical median of approximate 3 months in this patient population.

CytRx expects to report top-line progression-free survival (PFS) results from the phase IIb study in December and continue to evaluate the drug in other diseases.