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LOS ANGELES, May 21, 2015 /PRNewswire/ -- CytRx Corporation (NASDAQ: CYTR), a biopharmaceutical research and development company specializing in oncology, today announced positive updated results from its ongoing Phase 2 clinical trial with aldoxorubicin for the treatment of unresectable glioblastoma multiforme (GBM), a deadly form of brain cancer. The open-label, multisite trial is designed to investigate the preliminary efficacy and safety of aldoxorubicin in patients whose tumors have progressed following prior treatment with surgery, radiation and temozolomide.
Study subjects (n=18) have received between 1 and 14 cycles of aldoxorubicin, with 4 subjects continuing to receive aldoxorubicin treatment. Subjects received either 350 mg/m2 (260 mg/m2 doxorubicin equivalent) (n=6) or 250 mg/m2 (185 mg/m2 doxorubicin equivalent) (n=12) of aldoxorubicin intravenously on Day 1, and every 21 days thereafter until discontinuation. Notably, 2 subjects (11%) diagnosed with tumor progression following aldoxorubicin treatment (1 and 5 cycles, respectively) demonstrated no microscopic evidence of tumor tissue, a pathological complete response, when tissue was examined after resection. Fourteen of 18 subjects discontinued aldoxorubicin treatment, although there is a significant possibility that some of the patients experienced pseudo-progression. 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. Following discontinuation of aldoxorubicin treatment, 10 of 14 subjects received treatment with bevacizumab (Avastin®) for 1 to 14 cycles. Deaths have occurred in only 4 of 18 subjects (22%) to date, with survival duration so far of up to 10 plus months.
Aldoxorubicin was well tolerated at both dose levels with all adverse events consistent with known doxorubicin toxicities, but not cardiotoxity. Grade 3 or 4 adverse events were comprised primarily of neutropenia, anemia and fatigue and occurred mainly in the 350 mg/m2 dose group and were resolved before the next dose. Only two aldoxorubicin-related serious adverse events have occurred in the trial, and both resolved successfully.
"GBM is the most common and aggressive malignant primary brain cancer in humans and carries an extremely poor prognosis for the vast majority of diagnosed patients. Prognosis at recurrence is especially poor," said Morris D. Groves, M.D., Neuro-Oncologist, Texas Oncology-Austin Brain Tumor Center and co-principal investigator of the trial. "Pseudo-progression is commonly seen in CNS malignancies undergoing radiation therapy, and it mimics tumor progression, but it is thought to be a treatment-related reaction that could represent an active, inflammatory response against the tumor. The findings from this trial are early but exciting; the finding of no tumor cells in the resected GBM tumor samples after treatment with aldoxorubicin is worth further investigation. This suggests, somewhat paradoxically, that by binding to albumin, aldoxorubicin may allow doxorubicin to cross the blood:brain barrier and into the malignancy."
"These results suggest the possibility that the administration of Avastin® after treatment with aldoxorubicin could prolong survival in patients with relapsed GBM, and patient follow up is currently ongoing," said Daniel Levitt, M.D., Ph.D., CytRx Executive Vice President and Chief Medical Officer. "At the upcoming 2015 American Society of Clinical Oncology (ASCO) Annual Meeting, we will be convening with the study investigators to discuss the potential for a pivotal trial evaluating aldoxorubicin in combination with Avastin® for the treatment of relapsed GBM, with survival as the primary endpoint. We also look forward to submitting the results from this ongoing Phase 2 clinical trial for presentation at a neuro-oncology-focused medical meeting in 2015."
The primary objective of this Phase 2 trial is to determine progression-free survival (PFS) at 6 months and overall survival (OS) in patients with recurrent glioblastoma multiforme. The principal secondary objective is to evaluate the safety of aldoxorubicin in study patients as assessed by the frequency and severity of adverse events. Only patients who have not received prior treatment with bevacizumab (Avastin®) are eligible to participate in the trial. The clinical trial is expected to enroll up to 28 patients randomly assigned equally to receive either 350 mg/m2 (260 mg/m2 doxorubicin equivalent) or 250 mg/m2 (185 mg/m2 doxorubicin equivalent) of aldoxorubicin intravenously on Day 1, and every 21 days thereafter until evidence of tumor progression, unacceptable toxicity or withdrawal of consent. Tumor response is monitored every 6 weeks by MRI until disease progression occurs. The trial is being conducted at the John Wayne Cancer Center/Sarcoma Oncology Center in Santa Monica, CA, City of Hope in Duarte, CA, the Louisiana State University Health Sciences Center in New Orleans, LA, and Texas Oncology in Austin, TX.
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.
About Glioblastoma Multiforme
Glioblastoma is the most common and most malignant primary brain tumor in adults and afflicts more than 12,000 new patients in the U.S. annually. The median survival after diagnosis is approximately 14 months, despite patients subsequently receiving surgical resection, radiotherapy and chemotherapy. Limited efficacy of chemotherapeutic agents has been attributed to several contributing factors including insufficient drug delivery to the tumor site through the blood:brain barrier.
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 2,000 mg/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 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 has announced that it has received approval from the FDA to continue dosing patients with aldoxorubicin until disease progression in that clinical trial. CytRx is currently evaluating aldoxorubicin in a global Phase 2b clinical trial in small cell lung cancer, a Phase 2 clinical trial in HIV-related Kaposi's sarcoma, a Phase 2 clinical trial in patients with late-stage glioblastoma (brain cancer), a Phase 1b trial in combination with ifosfamide in patients with soft tissue sarcoma, and a Phase 1b trial in combination with gemcitabine in subjects with metastatic solid tumors. 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 clinical trial 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 plans to expand its pipeline of oncology candidates at its laboratory facilities in Freiburg, Germany, based on novel linker technologies that can be utilized with multiple chemotherapeutic agents and may allow for greater concentration of drug at tumor sites. 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 ongoing or future human testing of aldoxorubicin, including the Phase 2 clinical trial with aldoxorubicin for the treatment of unresectable GBM, might not produce results similar to those seen in past human or animal testing, including the preliminary results described in this press release, 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, risks related to lawsuits that have been brought against the Company and its officers and/or directors for alleged violations of the securities laws, 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.
Investor Relations:Argot PartnersMichelle Carroll[email protected]
Legend SecuritiesJohn Columbia800-385-5790 ext 164718-233-2677 (Direct)[email protected]
Media:Argot PartnersEliza Schleifstein[email protected]
Company Contact:CytRx CorporationDavid J. HaenVice President, Business Development and Investor Relations310-826-5648, [email protected]
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Study subjects (n=18) have received between 1 and 14 cycles of aldoxorubicin, with 4 subjects continuing to receive aldoxorubicin treatment. Subjects received either 350 mg/m2 (260 mg/m2 doxorubicin equivalent) (n=6) or 250 mg/m2 (185 mg/m2 doxorubicin equivalent) (n=12) of aldoxorubicin intravenously on Day 1, and every 21 days thereafter until discontinuation. Notably, 2 subjects (11%) diagnosed with tumor progression following aldoxorubicin treatment (1 and 5 cycles, respectively) demonstrated no microscopic evidence of tumor tissue, a pathological complete response, when tissue was examined after resection. Fourteen of 18 subjects discontinued aldoxorubicin treatment, although there is a significant possibility that some of the patients experienced pseudo-progression. 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. Following discontinuation of aldoxorubicin treatment, 10 of 14 subjects received treatment with bevacizumab (Avastin®) for 1 to 14 cycles. Deaths have occurred in only 4 of 18 subjects (22%) to date, with survival duration so far of up to 10 plus months.
Aldoxorubicin was well tolerated at both dose levels with all adverse events consistent with known doxorubicin toxicities, but not cardiotoxity. Grade 3 or 4 adverse events were comprised primarily of neutropenia, anemia and fatigue and occurred mainly in the 350 mg/m2 dose group and were resolved before the next dose. Only two aldoxorubicin-related serious adverse events have occurred in the trial, and both resolved successfully.
"GBM is the most common and aggressive malignant primary brain cancer in humans and carries an extremely poor prognosis for the vast majority of diagnosed patients. Prognosis at recurrence is especially poor," said Morris D. Groves, M.D., Neuro-Oncologist, Texas Oncology-Austin Brain Tumor Center and co-principal investigator of the trial. "Pseudo-progression is commonly seen in CNS malignancies undergoing radiation therapy, and it mimics tumor progression, but it is thought to be a treatment-related reaction that could represent an active, inflammatory response against the tumor. The findings from this trial are early but exciting; the finding of no tumor cells in the resected GBM tumor samples after treatment with aldoxorubicin is worth further investigation. This suggests, somewhat paradoxically, that by binding to albumin, aldoxorubicin may allow doxorubicin to cross the blood:brain barrier and into the malignancy."
"These results suggest the possibility that the administration of Avastin® after treatment with aldoxorubicin could prolong survival in patients with relapsed GBM, and patient follow up is currently ongoing," said Daniel Levitt, M.D., Ph.D., CytRx Executive Vice President and Chief Medical Officer. "At the upcoming 2015 American Society of Clinical Oncology (ASCO) Annual Meeting, we will be convening with the study investigators to discuss the potential for a pivotal trial evaluating aldoxorubicin in combination with Avastin® for the treatment of relapsed GBM, with survival as the primary endpoint. We also look forward to submitting the results from this ongoing Phase 2 clinical trial for presentation at a neuro-oncology-focused medical meeting in 2015."
The primary objective of this Phase 2 trial is to determine progression-free survival (PFS) at 6 months and overall survival (OS) in patients with recurrent glioblastoma multiforme. The principal secondary objective is to evaluate the safety of aldoxorubicin in study patients as assessed by the frequency and severity of adverse events. Only patients who have not received prior treatment with bevacizumab (Avastin®) are eligible to participate in the trial. The clinical trial is expected to enroll up to 28 patients randomly assigned equally to receive either 350 mg/m2 (260 mg/m2 doxorubicin equivalent) or 250 mg/m2 (185 mg/m2 doxorubicin equivalent) of aldoxorubicin intravenously on Day 1, and every 21 days thereafter until evidence of tumor progression, unacceptable toxicity or withdrawal of consent. Tumor response is monitored every 6 weeks by MRI until disease progression occurs. The trial is being conducted at the John Wayne Cancer Center/Sarcoma Oncology Center in Santa Monica, CA, City of Hope in Duarte, CA, the Louisiana State University Health Sciences Center in New Orleans, LA, and Texas Oncology in Austin, TX.
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.
About Glioblastoma Multiforme
Glioblastoma is the most common and most malignant primary brain tumor in adults and afflicts more than 12,000 new patients in the U.S. annually. The median survival after diagnosis is approximately 14 months, despite patients subsequently receiving surgical resection, radiotherapy and chemotherapy. Limited efficacy of chemotherapeutic agents has been attributed to several contributing factors including insufficient drug delivery to the tumor site through the blood:brain barrier.
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 2,000 mg/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 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 has announced that it has received approval from the FDA to continue dosing patients with aldoxorubicin until disease progression in that clinical trial. CytRx is currently evaluating aldoxorubicin in a global Phase 2b clinical trial in small cell lung cancer, a Phase 2 clinical trial in HIV-related Kaposi's sarcoma, a Phase 2 clinical trial in patients with late-stage glioblastoma (brain cancer), a Phase 1b trial in combination with ifosfamide in patients with soft tissue sarcoma, and a Phase 1b trial in combination with gemcitabine in subjects with metastatic solid tumors. 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 clinical trial 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 plans to expand its pipeline of oncology candidates at its laboratory facilities in Freiburg, Germany, based on novel linker technologies that can be utilized with multiple chemotherapeutic agents and may allow for greater concentration of drug at tumor sites. 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 ongoing or future human testing of aldoxorubicin, including the Phase 2 clinical trial with aldoxorubicin for the treatment of unresectable GBM, might not produce results similar to those seen in past human or animal testing, including the preliminary results described in this press release, 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, risks related to lawsuits that have been brought against the Company and its officers and/or directors for alleged violations of the securities laws, 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.
Investor Relations:Argot PartnersMichelle Carroll[email protected]
Legend SecuritiesJohn Columbia800-385-5790 ext 164718-233-2677 (Direct)[email protected]
Media:Argot PartnersEliza Schleifstein[email protected]
Company Contact:CytRx CorporationDavid J. HaenVice President, Business Development and Investor Relations310-826-5648, [email protected]
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