This is an open-label, multicenter, dose-escalation Phase 1/1b study in patients with acute
myelogenous leukemia (AML)/MDS or non-Hodgkin Lymphoma (NHL), intended to investigate safety,
pharmacokinetics, and the pharmacodynamic effects of FT-1101 administered via one or more
intermittent dosing schedules alone and in combination with azacitidine. Once the MTD has
been established for a treatment cohort, up to 20 additional patients may be enrolled in up
to 4 expansion cohorts each of select populations of patients with either AML/MDS or NHL at
the recommended dose for future studies to confirm safety.
Key Inclusion Criteria:
- Single agent (SA) Dose Escalation: Histologically or cytologically proven acute
leukemia or high-risk MDS as defined by the World Health Organization (WHO) criteria
and IPSS-R, respectively, that is relapsed or refractory (R/R) to standard therapy or
for whom standard treatments are contraindicated, OR
- Mature B-Cell non-Hodgkin Lymphoma that is Relapsed/Refractory to standard therapy
- AML SA expansion group 1: histologically or cytologically proven AML with a FLT3 ITD
or TKD mutation previously determined by local testing that is R/R to standard therapy
or for whom standard treatments are contraindicated
- AML SA expansion group 2: histologically or cytologically proven AML with intermediate
or unfavorable risk cytogenetics in the absence of a detectable FLT3 ITD or TKD
mutation as previously determined by local testing that is R/R to standard therapy or
for whom standard treatments are contraindicated
- NHL SA expansion: Mature B-cell NHL with the following histologies: primary
mediastinal lymphoma, DLBCL, and B-cell lymphoma not specified that is R/R to standard
therapy and for whom standard treatments are contraindicated or unavailable
- AML/MDS combination treatment (dose escalation and expansion): histologically or
cytologically proven AML or MDS as defined by WHO criteria and IPSS-R, respectively,
that is: R/R to standard therapy, or AML: who are unfit for, or unwilling to receive
standard induction therapy, or MDS: eligible to receive azacitidine
- Patients ≥ 18 years old
- Good kidney and liver function
- No prior organ allograft
- For fertile men and women, agreement to use effective contraceptive methods duration
of study participation and 90 days after
Key Exclusion Criteria:
- History of prior malignancy unless disease free for > or equal to 12 months or
considered surgically cured.
- Patients with symptomatic central nervous system (CNS) metastases or other tumor
location (such as spinal cord compression, other compressive mass, uncontrolled
painful lesion, bone fracture, etc.) necessitating an urgent therapeutic intervention,
palliative care, surgery or radiation therapy
- Treatment with major surgery (requiring general anesthesia) within one month prior to
study entry
- Previous treatment with any prior BET inhibitor therapy
- Patients unable to swallow oral medications, or patients with gastrointestinal
conditions (e.g. malabsorption, gastric or small bowel resection, etc.) deemed to
jeopardize intestinal absorption
- Congestive heart failure (New York Heart Association Class III or IV) or unstable
angina pectoris. Previous history of myocardial infarction within 1 year prior to
study entry, uncontrolled hypertension or uncontrolled arrhythmias
- Pulmonary disease (e.g. COPD, asthma, etc) that is not controlled (moderate to severe
symptoms) with current medication
- Known HIV positivity
- Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic
therapy
