This article is more than 5 years old. Information may no longer be current.
Sapacitabine fails to improve OS in elderly patients with AML
The phase 3 SEAMLESS study — designed to evaluate sapacitabine in elderly patients with newly diagnosed acute myeloid leukemia — failed to meet its primary endpoint of improvement in OS.
Sapacitabine (CYC682, Cyclacel Pharmaceuticals) is an orally available nucleoside analogue that acts through a novel DNA single-strand breaking mechanism to produce DNA double-strand breaks and/or checkpoint activation, causing cell death.
Researchers of the study randomly assigned 491 patients with AML who were aged 70 years or older to receive oral sapacitabine plus alternating cycles of IV decitabine or IV decitabine alone. All patients were not candidates for or refused intensive induction chemotherapy.
Patients in the treatment arm did not demonstrate improved OS compared with the control arm.
However, patients who had discontinued therapy at the time of analysis demonstrated an improved rate of complete remission.
Other endpoints, as well as the safety profile, appeared similar in both arms.
“We are disappointed not to have reached the primary endpoint of SEAMLESS. Nevertheless, the improvement in complete response rate and similar safety profile are encouraging,” Spiro Rombotis, president and CEO of Cyclacel, said in a company-issued press release.
A stratified subgroup analysis showed patients with low baseline peripheral white blood cell count achieved improved OS; however, patients with high white blood cell count demonstrated worsened outcomes.
“The results of the SEAMLESS phase 3 study demonstrate that sapacitabine is active and safe in elderly AML patients,” study chair Hagop Kantarjian, MD, professor and chair of the department of leukemia at The University of Texas MD Anderson Cancer Center, said in the release. “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. Additional analysis of stratified and exploratory subgroups is warranted to identify patients who are most likely to benefit from treatment with the experimental arm.”
Additional phase 2 studies are ongoing to evaluate sapacitabine for the treatment of myelodysplastic syndromes, cutaneous T-cell lymphoma and non–small cell lung cancer.
“Our clinical development strategy in oncology will now concentrate on our two ongoing, clinical programs in DNA damage response and transcriptional regulation, which include our area of historical expertise in CDK inhibitors,” Rombotis added. “These programs target biomarker-selected patients, such as those with BRCA mutations or resistance to existing cancer therapies.”