Synta Pharmaceuticals Corp. (NASDAQ: SNTA) announced that clinical results for two Phase 1 trials of STA-9090 in solid tumors, as well as 12 month updated survival results from the SYMMETRY trial of elesclomol in metastatic melanoma, were presented at the 2010 Annual Meeting of the American Society of Clinical Oncology (ASCO). STA-9090 is a potent, second generation, small molecule Hsp90 inhibitor that has shown strong activity in a broad range of preclinical solid and hematologic cancer models, including models highly resistant to treatment. The chemical structure of STA-9090 is unrelated to the first generation, ansamycin family of Hsp90 inhibitors (e.g., 17-AAG or IPI-504).
“The Phase 1 solid tumor results presented at ASCO demonstrate that STA-9090 is well-tolerated and has promising clinical activity,” said Jonathan Goldman, M.D., Premier Oncology and lead author on the Phase 1 trial with once-weekly dosing schedule. “Importantly, there has been no evidence of the severe hepatic or commonly occurring ocular toxicity that has been observed with other Hsp90 inhibitors. We have been encouraged by the evidence of single-agent clinical activity: Several patients who had progressed or failed to respond to multiple prior therapies experienced substantial tumor shrinkage and prolonged disease control with STA-9090; more than half of all evaluable patients experienced disease control. The scientific rationale for Hsp90 inhibition in cancer is very strong and the clinical data presented at ASCO suggest that STA-9090 may be the first compound to realize the potential of this target.”
“Based on the favorable safety profile and evidence of single-agent clinical activity, we believe that STA-9090 is the leading Hsp90 program in clinical development today, with exciting potential across a number of cancer indications,” said Vojo Vukovic, M.D., Ph.D., Senior Vice President and Chief Medical Officer, Synta Pharmaceuticals. “With eight trials currently underway and up to 15 expected by the end of the year, we have a robust clinical program designed to identify the patient populations likely to derive the greatest benefit from treatment with STA-9090, either as a single-agent or in combination.”
STA-9090 is currently being evaluated in four Phase 2 trials in solid tumor cancers – non-small cell lung cancer, gastrointestinal stromal tumors, colorectal cancer, and gastric cancer – and two trials in hematologic cancers. The two Phase 1 solid tumor trials are expected to complete in 2010. Preliminary Phase 2 results are expected later in 2010.
Synta also presented 12 month survival data from the Phase 3 SYMMETRY trial of elesclomol in metastatic melanoma. The results are consistent with earlier data presented at Melanoma XIII which demonstrate a differential response to treatment with elesclomol based on level of baseline lactate dehydrogenase (LDH). One or more clinical trials of elesclomol are expected to initiate in the second half of 2010.
All Synta posters presented at ASCO are available at www.syntapharma.com.
STA-9090 well-tolerated in Phase 1 once-weekly dosing solid tumor trial with encouraging signs of activity
STA-9090 was well-tolerated at dose levels of 7-216 mg/m2 administered on a once-weekly schedule. Dose-limiting toxicities of asthenia/fatigue and diarrhea were transient and reversible and there was no evidence of severe hepatic or ocular toxicities. Stable disease (SD) was seen in 23 of 42 evaluable patients, with 16 patients achieving SD for more than sixteen weeks (3 additional patients achieved SD at week 8 and remain on treatment). Two case studies were presented: a 66 year old male with bronchoalveolar non-small cell lung cancer who progressed on six prior treatment regimens with treatment duration on prior regimens of 2-4 months. This patient experienced 25% reduction in target lesion size following treatment with STA-9090 and remained on treatment for 13 months. A 49 year old male with a gastrointestinal stromal tumor (GIST), who had progressed on five prior treatment regimens, experienced an 18% reduction in target lesion size following treatment with STA-9090 and remained on treatment for 8 months. In addition, a patient with colon cancer achieved confirmed partial response (PR) per RECIST criteria, and three patients are continuing on study treatment.
STA-9090 in Phase 1 twice-weekly dosing solid tumor trial – encouraging signs of activity, MTD not achieved
Enrollment continues with STA-9090 well-tolerated at doses of 2-50 mg/m2.26 of 36 patients were evaluable for response as of March 15, 2010. The safety profile to date has been consistent with the results of the Phase 1 once-weekly dosing trial. Signs of clinical activity have included one patient with melanoma who achieved a confirmed partial response and 10 patients with stable disease. The maximum tolerated dose (MTD) has not yet been reached.
12 Month Survival Data – Phase 3 SYMMETRY trial of elesclomol in metastatic melanoma
Updated results are consistent with previously presented results (6-month follow-up): LDH remains an important predictor of Progression Free Survival (PFS) and Overall Survival (OS) outcome. SYMMETRY data continues to mature with time from last patient enrolled to data cutoff less than the median OS in the normal LDH patient population. The adverse event profile in the treatment arm (elesclomol + paclitaxel) was comparable to the control arm (paclitaxel alone) indicating that elesclomol is well-tolerated. The clinical observations regarding correlation of LDH levels with treatment outcomes are consistent with the underlying mechanism of action of elesclomol. Elesclomol disrupts energy metabolism in cancer cell mitochondria, and has been shown to be more active in cells where energy production occurs primarily through mitochondrial respiration (normoxic conditions; normal LDH) and less active in cells where energy production occurs primarily through glycolysis (hypoxic conditions; high LDH).
Synta Pharmaceuticals Corp.