A phase 2 study suggests that tipifarnib may be more beneficial for patients with CMML, MDS, or MPNs and RAS pathway mutations than the general population of patients with these disease.
Tipifarnib (Zarnestra) demonstrated modest efficacy benefit in patients with chronic myelomonocytic leukemia (CMML) and other myelodysplastic (MDS)/myeloproliferative neoplasms (MPNs) and was reasonably well-tolerated, according to results from a phase 2 study (NCT02807272). As a potent and highly selective farnesyl transferase inhibitor, tipifarnib therapy can be administered to work against the RAS pathway mutation that occurs in about 30% of patients with CMML and other MDS and MPNs. These mutations include NRAS, KRAS, CBL, and PTPN11. Earlier results of tipifarnib treatment showed that the agent is especially efficacious in patients with RAS wild-type CMML and in the MDS/MPN population, having high CXCR4/CXCR2 may be predictive of tipifarnib’s activity.
A total of 44 patients were included in the study and treated with tipifarnib 400 mg orally twice daily on days 1–21 of 28-day cycles. The primary end point was objective response rate (ORR) assessed per the MDS/MPN International Working Group (IWG) criteria in CMML patients with KRAS-positive or NRAS wild-type disease, and in the MDS/MPN population with high and low CXCR4/CXCR2. Secondary end points explored in the study include the adverse event profile of tipifarnib, progression-free survival (PFS) at 1 year, overall survival (OS) at 1 year, and duration of response (DOR).