Kura Oncology Reports Clinical Activity of Tipifarnib in Subsets of Pancreatic Cancer Associated with High CXCL12 Expression
January 18, 2019 at 10:00 am EST
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Kura Oncology, Inc. reported new findings identifying a potential association between CXCL12 expression and clinical benefit in patients with pancreatic cancer treated with tipifarnib. These findings are being presented at the 2019 Gastrointestinal Cancers Symposium in San Francisco. Tipifarnib has been shown to downregulate CXCL12, and previously reported data support tipifarnib as a CXCL12/CXCR4 pathway inhibitor. Elevated CXCL12 expression is known to be a poor prognosis factor in patients with pancreatic, Iung and esophageal-gastric cancers. In the specific context of pancreatic cancer, high CXCL12 expressing tumors may evade early diagnosis by decreasing abdominal pain through the attraction of pain-suppressing Schwann cells. To investigate the potential for association between CXCL12 expression and clinical benefit in pancreatic cancer patients, Kura conducted a retrospective analysis of study INT-11, a randomized, placebo-controlled Phase 3 study of gemcitabine plus tipifarnib compared with gemcitabine plus placebo in patients with advanced pancreatic cancer. A total of 688 pancreatic cancer patients were enrolled in study INT-11, of whom 155 reported no abdominal pain at study entry. Although no differences in survival were observed in the overall study, the absence of patient-reported abdominal pain at study entry was associated with higher median survival in the tipifarnib plus gemcitabine arm (10.2 months vs. 5.9 months, HR=0.52, p<0.0001), whereas no significant effect was observed in the placebo plus gemcitabine arm (6.0 months vs. 6.1 months), suggesting that the absence of abdominal pain may serve as a surrogate of clinical benefit from tipifarnib in pancreatic cancer. In addition, patients with nodal disease or distant metastases limited to the liver also appeared more likely to receive clinical benefit from tipifarnib. Significant clinical benefit was observed in 67 patients with nodal metastases (12.8 months vs. 8.2 months, HR=0.46, p=0.01) and in 233 patients with liver (only) metastases (6.8 months vs. 5.0 months, HR=0.7, p=0.02), respectively. Nodal and liver metastases of pancreatic cancer were found to express high levels of CXCL12. Analyzing data from The Cancer Genome Atlas (TCGA), Kura also found an association between high CXCL12 expression and pancreatic tumors with low KRAS mutant allele frequency (= 5%, representing approximately 30% of pancreatic cancer patients), which may help identify patients with tumors overexpressing CXCL12.
Kura Oncology, Inc. is a clinical-stage biopharmaceutical company. The Company is focused on precision medicine for the treatment of cancer. Its pipeline consists of small molecule product candidates that target cancer signaling pathways. Its product candidates include Ziftomenib, Tipifarnib and KO-2806. Ziftomenib, is a potent, selective, reversible and oral small molecule inhibitor that blocks the interaction of two proteins, menin and the protein expressed by the Lysine K-specific Methyl Transferase 2A gene, or KMT2A gene. Ziftomenib is a once-daily, oral drug candidate targeting the menin-KMT2A protein-protein interaction for the treatment of genetically defined acute myeloid leukemia patients with high unmet need. Tipifarnib is a potent, selective and orally bioavailable farnesyl transferase inhibitor (FTI). The KO-2806 is a next-generation FTI, which demonstrates improved potency, pharmacokinetic and physicochemical properties relative to earlier FTI drug candidates.
KURA ONCOLOGY, INC. 
