Hybrigenics has given an update on the Phase II clinical study of inecalcitol in chronic myeloid leukemia (CML) administered in addition to imatinib, the reference inhibitor of BCR-ABL kinase used as standard of care for CML.
The company explained that the ongoing, open-label Phase II study evaluates the efficacy of oral inecalcitol added to oral imatinib in CML patients who, after at least two years of treatment with imatinib alone, have achieved major molecular response (MMR) but not deep molecular response (DMR), with the objective to reach DMR within one year of treatment. Between the MMR and DMR levels, the disease is considered to be under control with continuous daily administration.
Twenty-one patients have been enrolled to date: twelve remain under treatment and nine have completed one year of treatment. At this intermediate stage of study, 43% of the patients (6 out of 14) have shown further decrease in BCR-ABL from MMR at three months, and after one year of treatment, 33% (3 out of 9) have demonstrated reduction in BCR-ABL beyond DMR, i.e. undetectable biomarker traces, said the company.
The company noted that these results can be compared with two recently published independent reports which demonstrate a simple 7.5% yearly increase in the percentage of patients reaching DMR under imatinib alone (Hochhaus et al., Leukemia, March 2016; Cortes et al., Journal of Clinical Oncology, July 2016).
Based on these intermediate results and a very low study drop-out rate, the sample size of this pilot study has been reduced to 42 patients, with a target completion in H2 2018. Hybrigenics’ Clinical Advisory Board has reviewed these preliminary observations and made suggestions to widen the scope of the potential clinical use of inecalcitol in CML.
Prof. A. Turhan, Head of the Division of Hematology, Paris-Sud Kremlin-Bicetre University Hospital said: “Inecalcitol should show similar effects in addition not only to imatinib, but also to second generation BCR-ABL kinase inhibitors, since we have demonstrated in Chronic Myeloid Leukemia stem cells isolated from patients that the same synergy exists between inecalcitol and all BCRABL kinase inhibitors,”.
“In Chronic Myeloid Leukemia, some Deep Molecular Responders relapse after having stopped
BCR-ABL kinase inhibitors. They have to resume treatment indefinitely and often the BCR-ABL
kinase inhibitors alone are not expected to permit further attempts at treatment free remission.
Adding inecalcitol in this clinical setting may ensure full efficacy and increase the chance for
durable cure,” explained Prof. M. Mauro, Leader, Myeloproliferative Neoplasms Program, Memorial
Sloan Kettering Cancer Center, New York.