ASH 2020: Early phase studies show promise in acute myeloid leukaemia

6 Dec 2020
ASH 2020: Early phase studies show promise in acute myeloid leukaemia

Eunice Wang, MD, Chief of Leukemia and Director of Infusion Services at Roswell Park Comprehensive Cancer Center, is leading multiple research efforts focused on different treatment approaches for acute myeloid leukaemia (AML) patients.

Today, during the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, which is being held virtually, she is presenting data on two ongoing studies incorporating new treatment options.

KOMET-001 (NCT04067336) is an ongoing phase I/IIA open-label study evaluating KO-539, a once-daily oral drug, in adult AML patients at Roswell Park and select other sites in the U.S. and Europe. KO-539 is a novel experimental inhibitor of the menin-KMT2A complex, which is dysregulated in acute leukemias characterised by rearrangements in the MLL gene and mutations in the NPM1 gene.

The phase I dose-escalation aims to assess safety and tolerability, characterise the pharmacokinetics, and determine a recommended phase II dose. Researchers will examine anti-leukaemic activity, pharmacokinetics, safety and tolerability in patients with select genetic subtypes of AML during the phase IIA dose expansion.

Dr. Eunice Wang, Chief of Leukemia at Roswell Park Comprehensive Cancer Center, is presenting findings from early-phase studies of new AML treatment options at the ASH 2020 virtual meeting.

“Preliminary results demonstrate that the drug appears to be safe and well-tolerated in adult patients with relapsed/refractory AML failing 3-7 prior lines of therapy,” says Dr. Wang. “None of 12 patients treated to date have discontinued therapy due to toxicity. Moreover, six of eight evaluable patients to date have shown some evidence of anti-leukaemic activity, with two individuals achieving complete remissions on therapy. This promising trial continues to enrol.”

Dr. Wang will also present early findings from the randomised, multicentre, open-label phase III LACEWING study exploring the efficacy of gilteritinib, a FLT3 inhibitor, combined with low-dose chemotherapy compared to low-dose chemotherapy alone.

Eligible patients include those with newly diagnosed FLT3 mutant AML who are considered unfit for intensive chemotherapy.

The primary objective of this study was overall survival. Secondary endpoints included event-free survival, best response, remission rates and duration, transfusion conversion and maintenance rates, leukaemia-free survival, patient-reported fatigue, and safety/tolerability.

Patients in an initial safety cohort received gilteritinib (80-120 mg daily) plus the low-dose chemotherapy azacitidine.

Mature data presented today show that 10 of 15 patients (67%) achieved a complete response or complete response, with incomplete count recovery on therapy with a median overall survival of 10.4 months.

The adverse events observed by researchers were haematologic and no new safety signals have been associated with gilteritinib (120 mg daily) when combined with azacitidine.

Enrolment in the randomised portion of the LACEWING trial is ongoing, with 136 of 250 anticipated patients accrued to date.

Patients in this group will be randomised 2:1 to receive oral gilteritinib in combination with azacitidine.

Based on data from the safety cohort, patients will receive a gilteritinib dose of 120 mg daily alongside low-dose chemotherapy.

“It’s encouraging to see signals of efficacy and evidence of good tolerability in these emerging treatment options, especially for subgroups of patients with AML whose cancers have been especially resistant to other therapies,” notes Dr. Wang.

Source: Roswell Park Comprehensive Cancer Center