A phase 1/2 dose escalation / dose expansion study of Enzomenib (DSP-5336) in patients with acute leukemia.
Have a diagnosis of relapsed or refractory AML, ALL or acute leukemia of ambiguous lineage according to World Health Organization (WHO) 2022 classification, or, in selected sites and regions, a diagnosis of MDS or MM as determined by pathology review at the treating institution, and whose disease has progressed after available standard therapies known to be active for their AML, ALL, or acute leukemia of ambiguous lineage or, in selected sites and regions, for MM or MDS. If acute leukemia patients are transformation from MDS or other hematologic malignancies, patients need to receive available standard therapies as acute leukemia after AML transformation and before enrolling this trial. In regions or countries where required by regulatory authorities, participants must have a documented KMT2A (MLL) fusion or NPM1 mutation, including those with coexisting FLT3 genomic alterations and/or IDH1/2 mutation. Participants who are candidates for stem cell transplantation must have been offered this therapeutic option.
Patients with MDS must have bone marrow blasts ≥ 5%
Patients with MDS must have relapsed or refractory disease and have exhausted available standard therapies including at least 2 cycles of treatment with HMA
Have a confirmed diagnosis of multiple myeloma according to International Myeloma Working Group (IMWG) 2016 classification (Kumar, 2016) and whose disease has progressed after treatment with a minimum of 3 prior anti-myeloma regimens including a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and an anti-CD38 monoclonal antibody (mAb); patients must not be candidates for available therapies with established clinical benefit
Has a left ventricular ejection fraction (LVEF) <50%, as determined by ECHO
Histological diagnosis of acute promyelocytic leukemia
Received systemic calcineurin inhibitors within 2 weeks prior to the first dose of DSP 5336
Have abnormal ECGs at screening that are clinically significant, such as (QTc >480 msec, with QTc corrected according to Fridericia's formula (QTcF). For clinical sites in the UK, have abnormal ECGs at screening that are clinically significant, such as QTc ≥470 msec and ≥450 msec with QTc corrected according to Fridericia's formula (QTcF), for females and males, respectively. In addition, patients with a history of prolonged QT syndrome or who are required to take therapies associated with QT-interval prolongation are excluded.
Parallel
Enzomenib
DrugDSP-5336 orally
azoles
DrugPosaconazole, Voriconazole, or Fluconazole
Venetoclax
DrugVenetoclax orally
Gilteritinib
DrugGilteritinib orally
Azacitidine (AZA)
DrugAzacitidine orally
Intensive chemotherapy with 7 + 3
Drugchemotherapy
14
Treatment groupsSee each treatment group below.
Number of patients with adverse events and serious adverse events in Phase 1
Assessment of safety of DSP-5336 administered in participants with advanced hematologic malignancies by reporting of adverse events and serious adverse events in Phase 1
Determination of Recommended Phase 2 Dose (RP2D)
The RP2D is based on adverse events, pharmacokinetics, and clinical response
Determination of Recommended Phase 2 Dose (RP2D) for patients with relapse and refractory AML who are enrolled into the combination venetoclax and azacitidine arm
The RP2D is based on adverse events, pharmacokinetics, and clinical response
Determination of Recommended Phase 2 Dose (RP2D) for patients with relapse and refractory AML who are enrolled into the gilteritinib arm
The RP2D is based on assessment of Dose Limiting Toxicities
The maximum observed concentration (Cmax) of of DSP-5336, venetoclax and gilteritinib
Cmax of DSP-5336, venetoclax and gilteritinib are calculated from the individual concentration time curve
Area under the plasma concentration vs. time curve (AUClast) of DSP-5336, venetoclax and gilteritinib
The determination of AUClast using the linear/log trapezoidal rule
T(1/2) of DSP-5336, venetoclax and gilteritinib
Elimination half-life (t\[1/2\]) of DSP-5336, venetoclax and gilteritinib
The maximum observed concentration (Cmax) of of DSP-5336 in the presence of high-fat meal
Cmax of DSP-5336 is calculated from the individual concentration time curve
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