Japanese pharmaceutical firm Astellas has began its Phase III trial of gilteritinib (ASP2215) in patients with relapsed or refractory (R/R) acute myeloid leukaemia (AML).

Overall survival (OS) is the main focus of the Phase III trial.

Discovered through a research collaboration between Astellas and Kotobuki Pharmaceutical, gilteritinib is a receptor tyrosine kinase inhibitor of FLT3 and AXL, which are involved in cancer cell growth.

Astellas has exclusive global rights to develop, manufacture and potentially commercialise gilteritinib, which has shown inhibitory activity against internal tandem duplication (ITD) and tyrosine kinase domain (TKD), two common FLT3 mutations seen in up to a third of patients with AML.

"Overall survival (OS) is the main focus of the Phase III trial."

Phase III is an open-label, multicentre trial of gilteritinib in around 369 patients with FLT3-activating mutations in bone marrow or whole blood. It follows a Phase I/II trial evaluating the effects of single daily doses from 20mg to 450mg.

In the new trial, patients will be randomised in a 2:1 ratio to receive either 120mg of gilteritinib or salvage chemotherapy consisting of LoDAC, azacitidine, MEC (mitoxantrone, etoposide, and intermediate-dose cytarabine), or FLAG-IDA (fludarabine, cytarabine, and granulocyte colony-stimulating factor with idarubicin).

A parallel multi-dose expansion group was started based on the efficacy seen in the dose escalation phase.

Preliminary data from the Phase I/II trial showed a 57.5% overall response rate and a 47.2% composite complete response (CR) rate. The results were based on 106 patients with FLT3 mutations, who received doses at 80mg and over.

Median duration of response was 18 weeks across all doses, while median OS was about 27 weeks at 80mg and above in FLT3 mutation-positive patients.

The maximum tolerated dose was determined to be 300mg after two patients reached dose-limiting toxicity at 450mg.

Earlier this month, the Japanese Ministry of Health, Labour and Welfare (MHLW) selected gilteritinib as one of the first products designated for Sakigake, which can shorten the review period in prioritised consultation, substantial pre-application consultation and prioritised review.