A Phase 1/2 Study of Enzomenib (DSP-5336) in Patients With Acute Leukemia (Horizen-1)

Recruiting now · Phase 1/Phase 2

Conditions studied: Leukemia, Myeloid, Acute, Leukemia, Lymphocytic, Acute, Multiple Myeloma, Myelodysplastic Syndromes

In brief

A phase 1/2 dose escalation / dose expansion study of Enzomenib (DSP-5336) in patients with acute leukemia.

Key facts

Study ID

NCT04988555

Run by

Sumitomo Pharma America, Inc.

People needed

606

Starts

2022-02-28

Expected to finish

2027-12-31

Last updated by the study team

2026-03-24

Who can join

Age: 12 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• For patients in Phase I:
• 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.
• For patients with MDS (selected sites and regions):
• 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
• For patients with MM (selected sites and regions):
• 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
• Have measurable disease as defined in the protocol
• Meet the laboratory parameters set in the protocol
• For patients with relapsed/refractory AML in the venetoclax and azacitidine combination cohort (in countries and sites where permitted):
• Have MLLr or NPM1m.
• For patients with relapsed/refractory AML in the gilteritinib combination cohort (in countries and sites where permitted):
• Have MLLr or NPM1m AND any of the following FLT3 mutations: FLT3-ITD, FLT3-TKD/D835 or FLT3-TKD/I836.
• For patients with relapsed/refractory AML with NPM1 enrolled in the RP2D confirmation cohort:
• Must have ≥5% blasts in bone marrow by morphologic assessment
• Must not have received prior treatment with a menin inhibitor
• For patients with newly diagnosed AML:
• Must have AML as defined by WHO 2022 criteria with a documented MLLr or NPM1m (patients with AML characterized by MLL partial tandem duplications, MLL deletions, or trisomy 11 are not eligible)
• Must not have received treatment for AML with the exception of hydroxyurea for control of white blood cell counts.
• For patients in Phase 2:
• Have a confirmed diagnosis of relapsed AML or ALL according to WHO 2022 classification, as determined by pathology review at the treating institution, and who have ≥5% blasts by morphologic assessment in the bone marrow. Patients with extramedullary disease or peripheral blasts as the only manifestation of relapse are not eligible. Patients must have received clinically applicable standard therapies with confirmed survival benefit. Patients must not have had prior exposure to a menin inhibitor.
• Have a documented KMT2A (MLL)-fusion assessed at relapse or immediately prior to the determination of refractory status. KMT2A genetic alterations other than fusions (eg, KMT2A-PTD, amplification, point mutation) are not permitted.
• For all patients:
• Be > 18 years of age. For countries and sites where approved, for DSP-5336 monotherapy, acute leukemia patients ≥12 years of age who weigh ≥40 kg may be enrolled.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status ≤2.

You may not qualify if…

• 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.
• Note: In case of bundle branch block, QT interval correction can be performed.
• Has an active and uncontrolled, bacterial, viral, or fungal infection requiring parenteral therapy. Note: Patients must be afebrile with negative blood cultures at least 72 hours prior to Cycle 1 Day 1.
• Receives concurrent sensitive substrates with a narrow safety window or strong inhibitors or inducers of CYP3A4/5, including specifically: ketoconazole, isavuconazole and itraconazole. Other antifungals that are used as standard of care to prevent or treat infections are permitted. If a patient is on one of the excluded azole class antifungals, he/she can be taken off or switched to a permitted azole 7 or more days prior to first dose, then the patient could be allowed on study (Arm B) with approval of the medical monitor.
• Had major surgery within 28 days prior to the first dose of DSP-5336
• Has active central nervous system leukemia (prophylactic intrathecal chemotherapy is allowed).
• Underwent HSCT or chimeric antigen receptor cell (CAR-T) therapy or other modified T-cell therapy within 60 days prior to the first dose of DSP-5336. For clinical sites in the UK, underwent CAR-T therapy or other modified T-cell therapy within 6 months prior to the first dose of DSP-5336.
• Received a donor lymphocyte infusion within 28 days prior to the first dose of DSP-5336, or receiving immunosuppressive therapy post-HSCT at the time of screening, or with clinically active GVHD or GVHD requiring active medical intervention other than the use of topical steroids for ongoing cutaneous GVHD
• Received antineoplastic agents (except hormonal therapies as adjuvant maintenance for breast or prostate cancers if a patient is taking before starting study treatment, and hydroxyurea given for controlling blast cells) or other investigational treatment within 7 days or 5 half-lives, whichever is shortest, prior to the first dose of DSP-5336
• In the opinion of the treating investigator, have any concurrent conditions that could pose an undue medical hazard or interfere with interpretation of study results; these conditions include, but are not limited to: clinically significant non-healing or healing wounds; concurrent congestive heart failure (New York Heart Association Functional Classification Class III or IV; see Section 21.2); concurrent unstable angina; concurrent cardiac arrhythmia requiring treatment (excluding asymptomatic atrial fibrillation); recent (within the prior 6 months) myocardial infarction; acute coronary syndrome within the previous 6 months; significant pulmonary disease (shortness of breath at rest or on mild exertion), eg, due to concurrent severe obstructive pulmonary disease, concurrent hypertension not controlled with concomitant medication, or diabetes mellitus with more than 2 episodes of ketoacidosis in the prior 6 months
• Have a known detectable viral load for human immunodeficiency virus or hepatitis C, or evidence of hepatitis B surface antigen, all being indicative of active infection.
• For sites in Japan, Taiwan, and Korea only: Hepatitis B core (HBc) antibody or hepatitis B surface (HBs) antibody test should be performed if HBsAg is negative. If HBc antibody or HBs antibody test is positive, HBV DNA quantification test should be performed to confirm that HBV DNA is negative.
• Have severe dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or gastrointestinal absorption of drugs administered orally, including the inability to swallow oral medication
• Have cognitive, psychological, or psychosocial impediment that would impair the ability of the patient to receive therapy according to the protocol, or adversely affect the ability of the patient to comply with the informed consent process, protocol, or protocol-required visits and procedures
• Are pregnant or breastfeeding or planning to become pregnant. Note: Patients who are breastfeeding may be enrolled if they interrupt breastfeeding prior to the first dose of any study drugs and do not feed the baby with breast milk expressed after receiving the first dose of any study drugs. Breastfeeding should not be resumed for at least 6 months after the last dose of study drug
• Have any history or complication of interstitial lung disease (for sites in Japan in Phase 1 dose escalation).
• For clinical sites in the EU, have a history of Grade ≥ 2 drug-induced interstitial lung disease or Grade ≥ 2 non-infectious pneumonitis within 6 months of starting study treatment.
• Have a history of Torsades de Pointes
• Received systemic calcineurin inhibitors within 4 weeks prior to the first dose of DSP-5336
• Have plasma cell leukemia (>2.0 x 109 /L plasma cells in blood by standard differential) (for patients with MM)
• For patients intending to enroll into the combination cohort with gilteritinib: Patients must be gilteritinib-naïve or sensitive and have not received a FLT3 inhibitor in the relapsed refractory setting (prior FLT3 inhibitor in front line therapy is allowed)
• Have a known intolerance of hypersensitivity reaction to components of the investigational medicinal product

Where it is running

• MDACC — Houston, Texas, United States (enrolling)
• University of Virginia — Charlottesville, Virginia, United States (enrolling)
• TriStar Centennial Medical Center — Nashville, Tennessee, United States (enrolling)
• University of Miami — Miami, Florida, United States (enrolling)
• Huntsman Cancer Institute — Salt Lake City, Utah, United States (enrolling)
• Intermountain Healthcare — Salt Lake City, Utah, United States (enrolling)
• Hoag Family Cancer Center — Newport Beach, California, United States (enrolling)
• Medical University of South Carolina — Charleston, South Carolina, United States (enrolling)
• University of Maryland — Baltimore, Maryland, United States (enrolling)
• Johns Hopkins Main Center — Baltimore, Maryland, United States (enrolling)
• Colorado Blood Cancer Institute — Denver, Colorado, United States (enrolling)
• Massachusetts General Hospital — Boston, Massachusetts, United States (enrolling)
• Atlantic Health — Morristown, New Jersey, United States (enrolling)
• Rutgers Cancer Institute of New Jersey — New Brunswick, New Jersey, United States (enrolling)
• Roswell Park Comprehensive Cancer Center — Buffalo, New York, United States (enrolling)
• Northwestern — Chicago, Illinois, United States (enrolling)
• Sibley Memorial Hospital — Baltimore, Maryland, United States (enrolling)
• UNC Hospital — Chapel Hill, North Carolina, United States (enrolling)
• Duke University — Durham, North Carolina, United States (enrolling)
• Atrium Wake Forest Baptist Medical Center — Winston-Salem, North Carolina, United States (enrolling)
• The Ohio State University Comprehensive Cancer Center — Columbus, Ohio, United States (enrolling)
• Oncology Associates of Oregon — Eugene, Oregon, United States (enrolling)
• Sidney Kimmel Comprehensive Cancer Center — Philadelphia, Pennsylvania, United States (enrolling)
• Allegheny Health Network — Pittsburgh, Pennsylvania, United States (enrolling)
• Virginia Cancer Specialists — Fairfax, Virginia, United States (enrolling)

Full record on ClinicalTrials.gov

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