Synta Announces Initiation of Three Multicenter, Randomized Phase II/III Trials of Ganetespib in Acute Myeloid Leukemia (AML) and High Risk Myelodysplastic Syndrome (MDS)
- Studies Sponsored by Cardiff University and Supported by the Leukemia & Lymphoma Research Fund and Cancer Research UK -
LEXINGTON, Mass.--(BUSINESS WIRE)--Synta Pharmaceuticals Corp. (NASDAQ: SNTA) today announced the initiation of three multicenter, randomized trials supported by the Leukemia & Lymphoma Research Fund and Cancer Research UK, evaluating ganetespib in combination with chemotherapy in first-line treatment of patients with AML and high risk MDS. These trials are conducted under the auspices of the UK National Cancer Institute (NCRI) Haematological Oncology Study Group with investigators in Denmark, France, New Zealand, and the United Kingdom and under the sponsorship of Cardiff University, UK. Ganetespib, Synta’s lead anti-cancer drug candidate, inhibits the heat shock protein 90 (Hsp90) chaperone protein and is being studied in over 25 clinical trials, including an ongoing Phase 3 trial in advanced non-small cell lung cancer.
“The selection of ganetespib for three major potentially registration-enabling trials in AML is an exciting validation of the clinical potential of ganetespib, and reinforces our strategy of continuing to expand the depth and breadth of the ganetespib program through collaborations with strong groups of investigators”
The biologic heterogeneity of AML, a disease characterized by clonal accumulation and expansion of immature myeloid cells within the bone marrow, represents a major challenge in the advancement of treatment for patients with the disease. Treatment choice and outcome are substantially decided by age. However, with current standard of care, a long term remission is achieved in only 40% of younger patients (age <60 years) and in less than 10% of older patients (age ≥ 60 years).
Preclinical results from Synta and its collaborators, Alan K. Burnett of Cardiff University and Sanjay Bansal of the UT Health Science Center at San Antonio, have shown that ganetespib inhibits a number of cancer-promoting factors believed to contribute to the proliferation of leukemic cells and renders them more vulnerable to treatment with chemotherapy. In total, three randomized, multi-center clinical trials have recently been initiated or are expected to initiate in the coming months designed to evaluate the therapeutic potential of ganetespib in AML and high-risk MDS:
- The AML-LI (less intensive)-1 trial, ongoing, evaluates the combination of ganetespib with low dose cytarabine (Ara-C) vs. low dose Ara-C alone in patients who are not eligible for intensive chemotherapy and are traditionally not included in most trials. Up to 50 patients will be enrolled in the ganetespib arm, after which an interim analysis will be conducted to evaluate the potential of proceeding into a potentially registration-enabling extension. This interim analysis is expected to be conducted later in 2014.
- The AML-18 trial, expected to begin enrolling patients 1H 2014, will evaluate ganetespib with standard DA (daunorubin and Ara-C) in patients over 60 years old who can tolerate intensive chemotherapy vs. treatment with standard DA alone. Up to 200 patients are expected to be enrolled in the ganetespib arm. Results from a pilot study conducted in the UK under the auspices of the Cardiff Experimental Cancer Medicine Centre in 2012 confirmed the feasibility and safety of combining ganetespib with intensive chemotherapy in older patients with AML.
- The AML-19 trial, expected to begin enrolling patients in 2H 2014, will evaluate ganetespib in combination with conventional chemotherapy vs chemotherapy alone in younger patients with AML. The trial is expected to enroll up to 200 patients in the ganetespib arm and will be conducted by the UK NCRI Group, a network of over 100 institutions. Patients will receive ganetespib sequentially to standard intensive therapy, followed by ganetespib maintenance treatment. The objective is to identify if ganetespib reduces the risk of relapse in the overall population or in key subgroups, and as a result, improves overall survival, the primary endpoint.
“There is an urgent need to improve the outcome of patients with AML and high risk MDS, in both the young and the elderly,” said Professor Alan K. Burnett of Cardiff University in the UK, the Principal Investigator in the LI-1 trial. “The comprehensive research program developed by UK NCRI Group, supported by the Leukemia & Lymphoma Research Fund and Cancer Research UK, aims to achieve this goal by using ganetespib to target Hsp90, a chaperone protein critical for malignant growth of AML. This approach is supported by the preclinical findings in AML models as well as clinical results showing that ganetespib has a favorable safety profile and encouraging clinical activity in several other cancer types.”
“The selection of ganetespib for three major potentially registration-enabling trials in AML is an exciting validation of the clinical potential of ganetespib, and reinforces our strategy of continuing to expand the depth and breadth of the ganetespib program through collaborations with strong groups of investigators,” said Safi R. Bahcall, Ph.D., President and CEO of Synta. “Promising preclinical and early clinical results have been observed with ganetespib and other Hsp90 inhibitors in AML. We are pleased by the decision of the Leukemia & Lymphoma Research Fund, the Cancer Research UK, and the trial investigators to invest in moving ganetespib forward into three large, randomized trials, which we hope will ultimately lead to new options for patients with this devastating disease.”
Synta has established over 100 academic, preclinical collaborations investigating the science and potential applications of ganetespib. Over two dozen clinical trials sponsored by investigators, cooperative groups, or patient foundations are ongoing or planned for 2014.
About AML and MDS
AML is a rapidly progressing hematologic cancer characterized by uncontrolled proliferation of immature blast cells in the bone marrow. The American Cancer Society estimates approximately 14,590 new cases of AML and approximately 10,370 deaths in the U.S. in 2013. AML patients with relapsed or refractory disease and newly diagnosed AML patients over 60 years of age with poor prognostic risk factors typically die within one year, resulting in an acute need for new treatment options for these patients.
MDS is a hematopoietic stem cell neoplasm characterized by disordered and ineffective hematopoiesis which results in irreversible decline in the number and quality of blood-forming cells. Patients often develop severe anemia requiring frequent blood transfusions. In most cases progressive bone marrow failure results in neutropenia and thrombocytopenia, and in about one third of patients the disease progresses into AML, usually within a few years.
Ganetespib, an investigational drug candidate, is a selective inhibitor of heat shock protein 90 (Hsp90), a molecular chaperone which controls the folding and activation of a number of client proteins that drive tumor development and progression. Many solid and hematologic tumors are dependent on Hsp90 client proteins including proteins involved in “oncogene addiction” (ALK, HER2, mutant BRAF and EGFR, androgen receptor, estrogen receptor, and JAK2); proteins involved in resistance to chemotherapy and radiation therapy (ATR, BCL2, BRCA1/2, CDK1/4, CHK1, survivin, and WEE1); proteins involved in angiogenesis (HIF-1alpha, VEGFR, PDFGR, and VEGF); and proteins involved in metastasis (MET, RAF, AKT, MMPs, HIF-1alpha, and IGF-1R). In preclinical models, inhibition of Hsp90 by ganetespib results in the inactivation, destabilization, and eventual degradation of these cancer-promoting proteins. Ganetespib is being evaluated in trials in lung cancer, breast cancer, and other tumor types. The most common adverse event seen to date has been transient, mild or moderate diarrhea, which has been manageable with standard supportive care. Information on these trials can be found at www.clinicaltrials.gov. Ganetespib has received Fast Track designation from FDA for second-line treatment of non-small cell lung adenocarcinoma in combination with docetaxel.
About Synta Pharmaceuticals
Synta Pharmaceuticals Corp. is a biopharmaceutical company focused on discovering, developing, and commercializing small molecule drugs to extend and enhance the lives of patients with severe medical conditions, including cancer and chronic inflammatory diseases. Synta has a unique chemical compound library, an integrated discovery engine, and a diverse pipeline of clinical- and preclinical-stage drug candidates with distinct mechanisms of action and novel chemical structures. All Synta drug candidates were invented by Synta scientists using our compound library and discovery capabilities. For more information, please visit www.syntapharma.com.
Safe Harbor Statement
This media release may contain forward-looking statements about Synta Pharmaceuticals Corp. Such forward-looking statements can be identified by the use of forward-looking terminology such as "will", "would", "should", "expects", "anticipates", "intends", "plans", "believes", "may", "estimates", "predicts", "projects", or similar expressions intended to identify forward-looking statements. Such statements, including statements relating to the timing for conduct of the interim analysis in the AML-LI-1 trial and start of enrollment of the AML-18 and AML-19 trials, reflect our current views with respect to future events and are based on assumptions and subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such forward-looking statements, including those described in "Risk Factors" of our Form 10-K for the year ended December 31, 2012 as filed with the Securities and Exchange Commission. Synta undertakes no obligation to publicly update forward-looking statements, whether because of new information, future events or otherwise, except as required by law.