A Phase III trial evaluating Cyclacel’s lead anticancer candidate sapacitabine (CYC682) against acute myeloid leukemia (AML) missed its primary endpoint of increasing overall survival (OS). The firm said that while it will re-evaluate its investment in developing sapacitabine against blood cancers, it hasn’t yet written off the drug completely.
“We plan to discuss the data with European and U.S. regulatory authorities once subgroup analyses are completed over the next few months and will report our further plans as they develop,” stated Spiro Rombotis, president and CEO.
The Phase III SEAMLESS study compared a regimen of alternating cycles of sapacitabine and decitabine therapy with decitabine alone in AML patients aged 70 years and over who were not candidates for or refused intensive induction chemotherapy. While the sapacitabine regimen failed to increase OS significantly in comparison with decitabine monotherapy, it did improve the complete remission (CR) rate, a secondary endpoint. There was also an increase in OS in a stratified subgroup of the approximately two-thirds of study patients demonstrating low baseline peripheral white blood cell count.
“Additional analysis of stratified and exploratory subgroups is warranted to identify patients who are most likely to benefit from treatment with the experimental arm,” suggested professor Hagop Kantarjian, M.D., chair of the SEAMLESS study chair. Professor Kantarjian is professor and chair at the University of Texas MD Anderson Cancer Center’s department of leukemia. “Although the experimental arm of alternating decitabine–sapacitabine did not reach statistically significant superiority in overall survival, it is remarkable that an improvement in complete remission rate was observed.”
Cyclacel said it will now focus its oncology-related development on the ongoing Phase I anticancer programs in DNA damage response and transcriptional regulation, which both involve biomarker-selected patients. The firm expects to have enough cash to continue product development and operations through to the end of 2018.
In December 2016, Cyclacel reported positive preclinical data demonstrating the potential of its polo-like kinase (PLK) 1 inhibitor CYC140 as a targeted therapy for multiple cancer types.