Tipifarnib
Tipifarnib is an oral, investigational drug candidate that we are evaluating in multiple solid tumor and hematologic indications.
Tipifarnib blocks the activity of an enzyme called farnesyl transferase. Protein farnesylation is a key cell signaling process implicated in various cancer processes, including survival, growth and proliferation of tumor cells.
Tipifarnib has been studied in more than 5,000 oncology patients and was observed to have a manageable side effect profile. Clinical and preclinical data suggest that, in certain selected patient populations, tipifarnib has the potential to provide clinical benefit to cancer patients with limited treatment options.
At Kura we are using a precision medicine approach to develop tipifarnib for the treatment of patients with selected types of cancer, including the following indications:
- HRAS Mutant Squamous Head and Neck Cancer
Tipifarnib in Patients with HRAS Mutant Squamous Head and Neck Cancer
Tipifarnib is an oral, investigational drug candidate we are evaluating in patients with certain head and neck cancers that carry HRAS mutations.
HRAS is a proto-oncogene, which is a normal gene that can become an oncogene due to mutations or increased expression. Proto-oncogenes code for proteins that help to regulate cell growth and differentiation and HRAS is mutated and/or expressed in certain head and neck squamous cell carcinoma (HNSCC) tumors.
Although HRAS was discovered more than 40 years ago, no specific therapies have been developed that target tumors with the mutated form of the protein. Tipifarnib is a potent and highly selective inhibitor of farnesyltransferase, a critical enzyme for the activity of HRAS.
The relapsed and/or refractory HNSCC patient population has an overall survival of approximately six to eight months and existing therapeutic options, including new therapies such as immune therapy, typically show a response rate in the range of 10-20 percent.
Encouraging clinical activity of tipifarnib has been observed in patients with HRAS mutant head and neck squamous cell carcinoma (HNSCC) tumors. We are conducting a registration-directed clinical trial to evaluate the safety and activity of tipifarnib in patients with relapsed and/or refractory HRAS mutant HNSCC.
Tipifarnib in Patients with Other HRAS Mutant Squamous Cell Carcinomas
We are also evaluating tipifarnib in patients with certain HRAS mutant squamous cell carcinomas (SCCs) other than head and neck, including vulvar, penile, cutaneous and lung.
Preclinical and clinical data suggest that, among solid tumors with HRAS mutations, squamous cell tumors are sensitive tumors to treatment with tipifarnib, and treatment with tipifarnib can, in some patients, produce durable responses.
View research on tipifarnib in other HRAS mutant squamous cell carcinomas.
Tipifarnib in Patients with Peripheral T-Cell Lymphoma (PTCL)
In addition to our tipifarnib development program in HRAS mutant solid tumors, we are evaluating the potential utility of tipifarnib using CXCL12 pathway biomarkers in a number of indications, including relapsed or refractory Peripheral T-Cell Lymphomas (PTCL).
Encouraging preliminary data from the trial suggest that tipifarnib has anti-tumor activity in certain patients with:
- Angioimmunoblastic T-cell lymphomas (AITL), an aggressive form of PTCL often characterized by high levels of CXCL12 expression
- Peripheral T-cell Lymphomas Not Otherwise Specified (PTCL-NOS) with elevated levels of CXCL12 expression
View research on tipifarnib in PTCL.
Tipifarnib in Patients with Chronic Myelomonocytic Leukemia (CMML)
We are also exploring the utility of CXCL12 pathway biomarkers in patients with relapsed or refractory Chronic Myelomonocytic Leukemia (CMML).
Our goals are to validate the utility of CXCL12 pathway biomarkers as a strategy for patient enrichment in CMML, and then to extend the potential use of tipifarnib to other myeloid indications and settings.
Tipifarnib and KO-947 are investigational drug candidates and have not yet been approved for use by the U.S. Food and Drug Administration (FDA) or other regulatory authorities.
View research on tipifarnib in CMML.
Tipifarnib in Patients with Pancreatic Cancer
Elevated CXCL12 expression is known to be a poor prognosis factor in patients with certain solid tumors, including pancreatic, lung and esophageal-gastric cancers.
We have identified a potential association between CXCL12 expression and clinical benefit from tipifarnib in patients with pancreatic cancer. We believe these findings support the potential use of tipifarnib in a broader set of hematologic and solid tumor indications, including pancreatic cancer, in which the CXCL12 pathway plays a role in tumor initiation and progression, and we are exploring opportunities for further clinical development.
View research on tipifarnib in pancreatic cancer.
KO-539
KO-539 is a drug candidate that we are developing for treatment of certain kinds of leukemia.
KO-539 blocks the interaction of two proteins called menin and MLL that, together, are critically important for survival, growth and proliferation of certain kinds of leukemia cells.
We have generated preclinical data that support the potential anti-tumor activity of KO-539 in genetically defined subsets of acute leukemia, including those with rearrangements or partial tandem duplications in the KMT2A (MLL) gene as well as those with oncogenic driver mutations in genes such as NPM1.
Our goal is to identify indications with the potential for single-agent activity, which may enable accelerated development.
Our investigational new drug (IND) application for KO-539 has been cleared by the FDA and a Phase 1/2A clinical trial in patients with relapsed or refractory AML is underway.
View research on KO-539 (menin inhibitor).
KO-539 is an investigational drug candidate and has not yet been approved for use by the U.S. Food and Drug Administration (FDA) or other regulatory authorities.