Aldoxorubicin Continues To Demonstrate Positive Clinical Activity In Phase 2 Glioblastoma Trial

CytRx Corporation

, a biopharmaceutical research and development company specializing in oncology, today announced that it has achieved its target enrollment of 28 patients with unresectable glioblastoma multiforme (GBM), a deadly form of brain cancer, in its Phase 2 trial with aldoxorubicin. To date, aldoxorubicin has shown evidence of tumor shrinkage, and overall survival has not yet been reached. Additionally, an advisory board of neuro-oncologists recently met to review the updated Phase 2 results and concluded that aldoxorubicin should be evaluated in combination with Avastin® in what could potentially be a pivotal trial in patients with late-stage GBM. "The initial findings strongly indicate that aldoxorubicin has significant anti-tumor activity in patients with GBM," said Morris D. Groves, M.D., Neuro-Oncologist, Texas Oncology-Austin Brain Tumor Center and co-principal investigator of the trial. "Pseudo-progression prevented us from determining the true efficacy of this agent since subjects may have been removed from aldoxorubicin treatment prematurely. Adding Avastin® to aldoxorubicin may increase the uptake of this drug into tumors leading to improved efficacy. " The open-label, multisite single-arm trial is investigating the preliminary efficacy and safety of aldoxorubicin in patients whose tumors have progressed following prior treatment with surgery, radiation and temozolomide. Patients to date received from 1 to 20 cycles of either 350 mg/m2 (260 mg/m2 doxorubicin equivalents) (n=6) or 250 mg/m2 (185 mg/m2 doxorubicin equivalents) (n=22) of aldoxorubicin intravenously on Day 1, and every 21 days thereafter until discontinuation. Median overall survival (range: 1 to 16+ months) has not yet been reached. Fifty-seven percent (16 of 28) of patients continue to be followed for survival with six patients still receiving aldoxorubicin treatment. Clear evidence of pseudo-progression was demonstrated in the tumor lesions of at least 4 subjects either after surgical debulking or by Dynamic Susceptibility Contrast MRI. Other subjects demonstrated extensive tumor necrosis on pathology with small amounts of residual tumor. Pseudo-progression refers to post-treatment imaging changes in the tumor where the tumor appears larger compared to the pre-treatment baseline images. These changes can be misleading in that the tumor appears to get worse (true progression), when in fact the changes may be the result of tumor destruction and related swelling around the tumor bed. Aldoxorubicin was well tolerated at both dose levels, with all adverse events consistent with known doxorubicin toxicities. No subject has had a decrease in their cardiac function. At the 250 mg/m2 dose, the most common grade 3 or 4 adverse events included neutropenia, fatigue, thrombocytopenia and mucositis. All adverse events resolved prior to the subsequent dose of aldoxorubicin. Only four patients have had aldoxorubicin-related serious adverse events and all have been resolved successfully. An Advisory Board of neuro-oncology experts recently reviewed the data from this trial. They concluded that aldoxorubicin clearly demonstrated anti-tumor activity with a favorable safety profile and that a randomized, comparative pivotal trial combining aldoxorubicin with Avastin® compared to Avastin® in patients who have relapsed after initial therapy was warranted. "By adding Avastin® to a treatment regimen with aldoxorubicin, we may be able to improve upon the activity of the agents in these very needy patients," said Daniel Levitt, M.D., Ph.D., CytRx Executive Vice President and Chief Medical Officer. "We plan to develop a protocol for a comparative potential pivotal trial based on the positive feedback from our advisors. We look forward to discussing the protocol with regulatory agencies, like the FDA, once we have the final data from the Phase 2 trial." This Phase 2 study follows positive confirmatory results reported in 2013 from a preclinical study in which aldoxorubicin demonstrated statistically significant efficacy (p<.0001) in the treatment of rapidly growing human brain (glioblastoma) cancer in the brains of animals. In that study, animals treated with aldoxorubicin had median survival of more than 63 days, compared with approximately 25 days for animals treated with doxorubicin or saline. In addition, because aldoxorubicin uptake was confined to the tumor in the brain rather than normal brain tissue, the principal investigator concluded that aldoxorubicin has the potential to safely shrink glioblastoma tumors, which could dramatically prolong patient survival.