- Studies Sponsored by
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,
- 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
UKunder 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
“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
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.
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
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This media release may contain forward-looking statements about
Synta Pharmaceuticals Corp.
Mindy Kohl, 781-541-7213
Andrea Rabney, 212-600-1494
Eliza Schleifstein, 917-763-8106