Combination of tosedostat and LDAC results in overall response rate of 54% in elderly patients with AML

CTI BioPharma Corp. (CTI BioPharma) (NASDAQ and MTA: CTIC) today announced findings from an investigator-sponsored Phase 2 trial in patients with either primary (de novo) acute myeloid leukemia (AML) or AML that has evolved from myelodysplastic syndrome (MDS). Results showed the combination of tosedostat with low dose cytarabine/Ara-C (LDAC) resulted in an overall response rate (ORR) of 54 percent in elderly patients with AML – with 45 percent of patients achieving durable complete responses (CR). These final results were presented by Dr. Giuseppe Visani, Director of Hematology and Stem Cell Transplant Center at AORMN, Pesaro, Italy in a poster session (abstract #P564) during the 20th Congress of the European Hematology Association (EHA), June 11-14, 2015 in Vienna, Austria.

AML is the most common acute leukemia affecting adults, and its incidence increases with age. AML may develop from the progression of other diseases, such as MDS, which is a blood cancer that also affects the bone marrow and leads to a decrease in circulating red blood cells. Tosedostat is a potential first-in-class selective inhibitor of aminopeptidases, which are required by tumor cells to provide amino acids necessary for growth and tumor cell survival.

"Both the types and length of responses in this trial with tosedostat are very encouraging – particularly given the limited options and poor outcomes historically observed in elderly patients with acute myeloid leukemia, either de novo or secondary after myelodysplastic syndrome," said Dr. Visani. "Importantly, through this study we have also identified potential biomarkers that may help identify high-risk patients in which we are more likely to see these clinically meaningful results – the findings of which are quite compelling and warrant further study."

Findings Presented at EHA
Final results presented at EHA show that responding patients had a significant improvement in overall survival based on response rates compared to non-responding patients (p=0.018). In the intent-to-treat population (ITT), the ORR was 54 percent – with CR observed in 45 percent of patients (n=15/33). In the responding patients, the median time for achieving best response was 74 days (range: 22-145 days) and 55 percent (n=10/18) were still in remission after a median follow-up of 319 days. Safety analysis show that tosedostat in combination with LDAC was generally well tolerated. The primary adverse events observed were pneumonitis (12 percent), cardiac (6 percent), brain hemorrhage (3 percent), and asthenia (3 percent).

One of the secondary endpoints was to identify possible biomarkers associated with sensitivity and/or drug resistance. A gene expression profile (GEP) was performed on purified AML cells obtained from 29 patients. Analysis of these patient cells identified a molecular signature associated with clinical response (CR vs. no CR). Based on the differentially expressed genes (n=212), samples were divided according to either CR or no CR. Results showed that these differentially expressed genes were associated with relevant biological functions and pathways – including B-catenin (beta-catenin), TNFA-NFkB, ERB2, inflammatory response, and epithelial-mesenchimal transition – and showed that the achievement of a CR could be efficiently predicted by GEP.

"The results observed with tosedostat in acute myeloid leukemia add to a growing body of data showing the anti-tumor activity of this aminopeptidase inhibitor and the potential of using this approach to treat blood-related cancers," Alan K. Burnett, M.D., Global Lead for Myeloid Diseases at CTI BioPharma. "Based on the clinical data observed to date, we are advancing the development for tosedostat including the potential for a Phase 3 registrational study for primary acute myeloid leukemia or acute myeloid leukemia that evolves from myelodysplastic syndrome."


CTI BioPharma Corp.


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