AML, CMML, MDS
Conditions
Brief summary
This is a Phase 1/2a dose-escalation study of E6201, a dual mitogen-activated protein kinase/extracellular-signal regulated kinase 1 (MEK1) and FMS-like tyrosine kinase 3 (FLT3) inhibitor, in subjects with advanced hematologic malignancies with documented FLT3 and/or rat sarcoma (Ras) mutations. The Phase1 portion of the study will be a safety run-in (up to 30 subjects) to establish a recommended Phase 2 dose (RP2D). The Ph. 2a portion of the study will evaluate three specific patients groups: Cohort 1 will enroll patients with relapsed or refractory AML and confirmed FLT3 mutation (with or without a Ras mutation) without prior exposure to a FLT3 inhibitor; Cohort 2 will enroll patients with relapsed or refractory AML and confirmed FLT3 mutation (with or without a Ras mutation) with prior exposure to a FLT3 inhibitor; Cohort 3 will enroll patients with relapsed or refractory AML with a confirmed Ras mutation and no FLT3 mutation.
Detailed description
Phase 1 (Safety Run-In): Following Screening, a total of up to 30 subjects in up to 5 dose cohorts to establish the RP2D. The safety run-in phase will be a standard 3+3 cohort design. Phase 2a (Expansion): Once the Phase 1 Safety Run-In portion of the study is complete and an RP2D is established, additional subjects will be enrolled into the Phase 2 Expansion portion in three cohorts. Cohort 1 will enroll up to 26 patients with relapsed or refractory AML and confirmed FLT3 mutation (with or without a Ras mutation) without prior exposure to a FLT3 inhibitor. Cohort 2 will enroll up to 26 patients with relapsed or refractory AML and confirmed FLT3 mutation (with or without a Ras mutation) with prior exposure to a FLT3 inhibitor. Cohort 3 will enroll up to 10 patients with relapsed or refractory AML with a confirmed Ras mutation and no FLT3 mutation. Cohort 1 and 2 of the Expansion Phase will incorporate a Simon 2-stage optimal design. Subjects with AML enrolled in the Phase 1 portion of the study at the RP2D will count towards the Phase 2a accrual for the appropriate cohort. Subjects will receive E6201 weekly or bi-weekly on a 28-day schedule, with the schedule and dose level established in the Safety Run-In portion of the study. Disease assessments, including analysis of blood and bone marrow samples, will be performed at the end of Cycles 1 and 3 and every 2 cycles thereafter. Disease assessments may be made at other time points at the discretion of the Investigator. Subjects who demonstrate clinical benefit (objective response or stable disease) will be allowed to continue therapy with E6201 until progression of disease, observation of unacceptable adverse events, intercurrent illness or changes in the patient's condition that prevents further study participation. During the study, ECGs will be performed, blood will be collected for hematology, serum chemistry, pharmacokinetics and pharmacodynamics assessments, and bone marrow will be collected for the assessment of disease response and mutational status.
Interventions
DRUGE6201
Single Group Assignment
Sponsors
Spirita Oncology, LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Males and females ≥ 18 years of age * Phase 1: Confirmed relapsed or refractory AML with a documented FLT3 and/or Ras mutation, or ≥ 60 years with newly diagnosed FLT3+ and/or Ras+ AML and not eligible for standard induction chemotherapy or FLT3+ and/or Ras+ higher-risk MDS/CMML (defined as ≥ 10% marrow blasts or ≥ 5% peripheral blood blasts or Revised International Prognostic Scoring System \[IPSS-R\] score ≥ 3.5) and relapsed or refractory to prior therapy * Phase 2: Confirmed relapsed or refractory AML with a documented FLT3 and/or Ras mutation, or age ≥ 60 years with newly diagnosed FLT3+ and/or Ras+ AML and not eligible for standard induction chemotherapy * At least 3 weeks beyond the last cancer treatment for the disease under study, major surgery and recovered from all acute toxicities (≤ Grade 1) by first dose of study drug (C1D1). Hydroxyurea used to control peripheral blast counts is permitted during the first 2 cycles. * Adequate performance status Eastern Cooperative Oncology Group (ECOG) ≤ 2 * Adequate renal and hepatic function: * creatinine ≤ 1.5 mg/dL OR calculated creatinine clearance ≥ 45 mL/minute * total bilirubin ≤ 2 times the upper limit of normal (ULN) unless due to Gilbert's disease or thought to be due to underlying AML * ALT and AST ≤ 5 times ULN * Negative serum pregnancy test within 14 days prior to the first dose of study therapy for women of child-bearing potential (WCBP). Sexually active WCBP and male subjects must agree to use adequate methods to avoid pregnancy throughout the study and for 28 days after completion of study treatment. * Ability to provide written informed consent
Exclusion criteria
* History of clinically significant cardiac impairment, congestive heart failure (CHF) New York Heart Association (NYHA) Class III or IV, unstable angina, or myocardial infarction during the previous 6 months, or serious cardiac arrhythmia * QT interval corrected for rate (QTc) ≥ 450 msec for males and ≥ 460 msec for females on the ECG obtained at Screening using Fridericia method for QTc calculation (average of 3 readings) * Concomitant medication(s) that may cause QTc prolongation or induce Torsades de Pointes with the exception of anti-microbials used as standard of care to prevent or treat infections and other such drugs that are considered by the investigator to be essential for the care of the patient. However, if such medications are deemed to be necessary during the study, more extensive ECG monitoring will be added during the period of concomitant drug administration. * Presence of active central nervous system (CNS) leukemia. Subjects adequately treated for CNS leukemia documented by 2 consecutive cerebrospinal fluid samples negative for leukemia cells are eligible. Subjects with no history of CNS leukemia will not be required to undergo cerebrospinal fluid sampling for eligibility. * Known positive for human immunodeficiency virus (HIV), hepatitis B virus surface antigen (HBsAg), or hepatitis C virus HCV) * Active, uncontrolled infection * Known hypersensitivity to any study drug component * History of another malignancy; Exception: Patients disease-free for 2 years or treated in situ carcinoma * Any other medical intervention or other condition which, in the opinion of the Principal Investigator, could compromise adherence to study requirements or confound the interpretation of study results * Pregnancy or lactation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose (MTD) of E6201 | Up to 6 weeks for each dose cohort | Phase 1 (Safety Run-In) was conducted in 5 dose cohorts in up to 30 subjects in a standard 3+3 dose-escalation design to establish an MTD and recommended Phase 2 dose (RP2D). Safety assessed through the monitoring of adverse events (AEs), serious adverse events (SAEs), clinical laboratory parameters (hematology and serum chemistry), vital sign measurements, electrocardiograms (ECGs) and physical examinations. |
| Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | Up to 6 weeks for each dose cohort | A DLT was defined as any one of the following events: prolonged myelosuppression (as defined by the National Cancer Institute \[NCI\] criteria specific for leukemia, i.e., marrow cellularity \< 5% at ≥ 6 weeks from start of therapy without evidence of leukemia); ≥ Grade 3 non-hematologic toxicity (excluding Grade 3 nausea, vomiting or diarrhea that is adequately controlled with supportive care and resolves to ≤ Grade 2 within 48 hours, or Grade 3 electrolyte disturbances responsive to correction within 24 hours); ≥ Grade 3 liver function tests (LFTs) lasting \> 7 days; treatment interruption \> 14 days due to toxicity; or other important medical event. DLTs were collected to determine the MTD which is defined as the dose level below the dose at which ≥ 2 of 6 patients in a dose cohort experienced a DLT. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival | From Cycle 1 Day 1 (C1D1) until death or study closure, up to 26 months | Length of time from the date of first administration of study drug to the first evidence of disease progression or death, whichever is earlier |
| Overall Survival | From C1D1 until death or study closure, up to 26 months | Length of time from the date of first administration of study drug to the date of death from any cause |
| Pharmacokinetic Profile of E6201 in Plasma: Cmax | Assessed at Cycle 1 Days 1 and 15, Cycle 2 Day 1, pre-dose, 5 minutes following the end of the 2-hour infusion, 2, 4, 8 and 24 hours post-infusion. Summary PK parameters for Cycle 1 Day 1 reported. | Cmax: Maximum measured plasma concentration over the collection period |
| Pharmacokinetics of E6201 in Plasma: Tmax | Assessed at Cycle 1 Days 1 and 15, Cycle 2 Day 1, pre-dose, 5 minutes following the end of the 2-hour infusion, 2, 4, 8 and 24 hours post-infusion. Summary PK parameters for Cycle 1 Day 1 reported. | Tmax: Time to maximum measured plasma concentration |
| Pharmacokinetic Profile of E6201 in Plasma: AUCT | Assessed at Cycle 1 Days 1 and 15, Cycle 2 Day 1, pre-dose, 5 minutes following the end of the 2-hour infusion, 2, 4, 8 and 24 hours post-infusion. Summary PK parameters for Cycle 1 Day 1 reported. | Area under the plasma concentration versus time curve (AUC) to the last measurable concentration over the sampling time-interval. |
| Pharmacokinetic Profile of E6201 in Plasma: AUCI | Assessed at Cycle 1 Days 1 and 15, Cycle 2 Day 1, pre-dose, 5 minutes following the end of the 2-hour infusion, 2, 4, 8 and 24 hours post-infusion. Summary PK parameters for Cycle 1 Day 1 reported. | AUCI: The area under the concentration versus time curve from time 0 to infinity |
| Pharmacokinetic Profile of E6201 in Plasma: T1/2 | Assessed at Cycle 1 Days 1 and 15, Cycle 2 Day 1, pre-dose, 5 minutes following the end of the 2-hour infusion, 2, 4, 8 and 24 hours post-infusion. Summary PK parameters for Cycle 1 Day 1 reported. | T1/2: The apparent first-order elimination half-life |
| Pharmacokinetic Profile of E6201 in Plasma: CLobs | Assessed at Cycle 1 Days 1 and 15, Cycle 2 Day 1, pre-dose, 5 minutes following the end of the 2-hour infusion, 2, 4, 8 and 24 hours post-infusion. Summary PK parameters for Cycle 1 Day 1 reported. | Clearance observed (CLobs): Total body clearance for extravascular administration |
| Pharmacokinetic Profile of E6201 in Plasma: VDobs | Assessed at Cycle 1 Days 1 and 15, Cycle 2 Day 1, pre-dose, 5 minutes following the end of the 2-hour infusion, 2, 4, 8 and 24 hours post-infusion. Summary PK parameters for Cycle 1 Day 1 reported. | Measurement of apparent volume of distribution observed (VDobs) |
| Overall Response Rate | At the end of C1 and every 2 cycles thereafter through 6 months following last dose of study drug | For acute myeloid leukemia (AML): Revised Recommendations of the International Working Group (IWG) Response Criteria for AML: CR: Free of leukemia-related symptoms, absolute neutrophil count (ANC) \> 1.0 x 10\^9/L, platelet count ≥ 100 x 10\^9/L, normal bone marrow with \< 5% blasts and no Auer rods. CRi: As per CR but w/ residual thrombocytopenia (platelet count \<100 x 10\^9/L) or residual neutropenia (ANC \<1.0 x 10\^9/L). PR: ≥50% decrease bone marrow blasts to 5 - 25% abnormal cells, or CR w/ ≤ 5% blasts if Auer rods present. For myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML): Modified IWG Response Criteria for MDS: CR: Free of leukemia-related symptoms, ANC ≥1.0 x 10\^9/L, platelet count ≥100 x 10\^9/L, bone marrow ≤5% myeloblasts, normal maturation of all cell lines, hemoglobin ≥ 11g/dL, no blasts in the peripheral blood. PR: All CR criteria w/ ≥50% decrease in bone marrow blasts over pre-treatment, but still \> 5%. |
| Number of Participants With Suppression of pERK at 24 Hours Post-dose | Cycle 1 Day 1, 24 hours post-dose. | Measurement of phospho-ERK (pERK) in blood assessed by Western blot at 24 hours post-dose |
| Number of Participants With Suppression of pFLT3 at 4 Hours Post-dose | Cycle 1 Day 1, 4 hours post-dose. | phospho-FLT3 (pFLT3) in blood assessed by Western blot at 4 hours post-dose |
| Number of Participants With Suppression of pFLT3 at 24 Hours Post-dose | Cycle 1 Day 1, 24 hours post-dose. | phospho-FLT3 (pFLT3) in blood assessed by Western blot at 24 hours post-dose |
| Number of Participants With Suppression of pAKT at 4 Hours Post-dose | Cycle 1 Day 1, 4 hours post-dose. | phospho-AKT (pAKT) in blood assessed by Western blot at 4 hours post-dose |
| Number of Participants With Suppression of pAKT at 24 Hours Post-dose | Cycle 1 Day 1, 24 hours post-dose. | phospho-AKT (pAKT) in blood assessed by Western blot at 24 hours post-dose |
| Number of Participants With Suppression of pERK by PIA at 4 Hours Post-dose | Cycle 1 Day 1, 4 hours post-dose. | Blood assay: Plasma inhibitory assay (PIA) measuring pERK in blood at 4 hours post-dose |
| Number of Participants With Suppression of in pERK by PIA 24 Hours Post-dose | Cycle 1 Day 1, 24 hours post-dose. | Blood assay: Plasma inhibitory assay (PIA) measuring pERK in blood at 24 hours post-dose |
| Number of Participants With Suppression of pFLT3 by PIA at 4 Hours Post-dose | Cycle 1 Day 1, 4 hours post-dose. | Blood assay: Plasma inhibitory assay (PIA) measuring pFLT3 in blood at 4 hours post-dose |
| Number of Participants With Suppression of pFLT3 by PIA at 24 Hours Post-dose | Cycle 1 Day 1, 24 hours post-dose. | Blood assay: Plasma inhibitory assay (PIA) measuring pFLT3 in blood at 24 hours post-dose |
| Number of Participants With Suppression of pERK at 4 Hours Post-dose | Cycle 1 Day 1, 4 hours post-dose. | phospho-ERK (pERK) in blood assessed by Western blot at 4 hours post-dose |
| Duration of Response | At the end of C1 and every 2 cycles thereafter through 6 months following last dose of study drug | Length of time from the first evidence of objective response to the first evidence of progression |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: E6201 240 mg/m^2 Weekly Cohort 1: Participants were administered E6201 240 mg/m\^2 IV over 2 hours once weekly, on Days 1, 8, 15, and 22, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for study drug discontinued, and followed for up to 6 months after the last dose. | 7 |
| Cohort 2: E6201 320 mg/m^2 Weekly Cohort 2: Participants were administered E6201 320 mg/m\^2 IV over 2 hours once weekly, on Days 1, 8, 15, and 22, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for study drug discontinuation, and followed for up to 6 months after the last dose. | 10 |
| Cohort 3: E6201 160 mg/m^2 Twice Weekly Cohort 3: Participants were administered E6201 160 mg/m\^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for study drug discontinuation, and followed for up to 6 months after the last dose. | 3 |
| Cohort 4: E6201 240 mg/m^2 Twice Weekly Cohort 4: Participants were administered E6201 240 mg/m\^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for study drug discontinuation, and followed for up to 6 months after the last dose. | 3 |
| Cohort 5: E6201 320 mg/m^2 Twice Weekly Cohort 5: Participants were administered E6201 320 mg/m\^2 IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle) until progression of disease, toxicity or other reason for study drug discontinuation, and followed for up to 6 months after the last dose. | 4 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Cohort 1: E6201 240 mg/m^2 Weekly | Lack of Efficacy | 4 | 0 | 0 | 0 | 0 |
| Cohort 1: E6201 240 mg/m^2 Weekly | Prepare for HSCT | 1 | 0 | 0 | 0 | 0 |
| Cohort 1: E6201 240 mg/m^2 Weekly | Withdrawal by Subject | 2 | 0 | 0 | 0 | 0 |
| Cohort 2: E6201 320 mg/m^2 Weekly | Lack of Efficacy | 0 | 9 | 0 | 0 | 0 |
| Cohort 2: E6201 320 mg/m^2 Weekly | Withdrawal by Subject | 0 | 1 | 0 | 0 | 0 |
| Cohort 3: 160 mg/m^2 Twice Weekly | Lack of Efficacy | 0 | 0 | 3 | 0 | 0 |
| Cohort 4: 240 mg/m^2 Twice Weekly | Lack of Efficacy | 0 | 0 | 0 | 3 | 0 |
| Cohort 5: 320 mg/m^2 Twice Weekly | Lack of Efficacy | 0 | 0 | 0 | 0 | 3 |
| Cohort 5: 320 mg/m^2 Twice Weekly | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Cohort 1: E6201 240 mg/m^2 Weekly | Total | Cohort 5: E6201 320 mg/m^2 Twice Weekly | Cohort 4: E6201 240 mg/m^2 Twice Weekly | Cohort 3: E6201 160 mg/m^2 Twice Weekly | Cohort 2: E6201 320 mg/m^2 Weekly |
|---|---|---|---|---|---|---|
| Age, Continuous | 61.57 years STANDARD_DEVIATION 13.97 | 56.26 years STANDARD_DEVIATION 15.78 | 56.00 years STANDARD_DEVIATION 17.64 | 56.33 years STANDARD_DEVIATION 12.01 | 61.33 years STANDARD_DEVIATION 11.02 | 51.10 years STANDARD_DEVIATION 19.14 |
| Disease Type AML | 4 Participants | 24 Participants | 4 Participants | 3 Participants | 3 Participants | 10 Participants |
| Disease Type CMML | 2 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Disease Type MDS | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Eastern Cooperative Group (ECOG) Performance Status 0 | 2 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Eastern Cooperative Group (ECOG) Performance Status 1 | 5 Participants | 20 Participants | 4 Participants | 3 Participants | 2 Participants | 6 Participants |
| Eastern Cooperative Group (ECOG) Performance Status 2 | 0 Participants | 4 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants |
| Eastern Cooperative Group (ECOG) Performance Status 3 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Eastern Cooperative Group (ECOG) Performance Status 4 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 3 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 21 Participants | 4 Participants | 3 Participants | 2 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Prior Cancer Therapies All Prior Cancer Treatment Regimens | 3 Number of treatment regimens | 5 Number of treatment regimens | 4 Number of treatment regimens | 5 Number of treatment regimens | 4 Number of treatment regimens | 6.5 Number of treatment regimens |
| Prior Cancer Therapies Prior FLT3 Inhibitor Treatment Regimens | 1 Number of treatment regimens | 1 Number of treatment regimens | 1 Number of treatment regimens | 1 Number of treatment regimens | 1 Number of treatment regimens | 1 Number of treatment regimens |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 4 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 19 Participants | 3 Participants | 2 Participants | 3 Participants | 6 Participants |
| Region of Enrollment United States | 7 participants | 27 participants | 4 participants | 3 participants | 3 participants | 10 participants |
| Sex: Female, Male Female | 5 Participants | 14 Participants | 2 Participants | 1 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Male | 2 Participants | 13 Participants | 2 Participants | 2 Participants | 1 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 7 | 4 / 10 | 1 / 3 | 0 / 3 | 1 / 4 |
| other Total, other adverse events | 7 / 7 | 10 / 10 | 3 / 3 | 3 / 3 | 4 / 4 |
| serious Total, serious adverse events | 4 / 7 | 10 / 10 | 3 / 3 | 2 / 3 | 2 / 4 |
Outcome results
Primary
Maximum Tolerated Dose (MTD) of E6201
Phase 1 (Safety Run-In) was conducted in 5 dose cohorts in up to 30 subjects in a standard 3+3 dose-escalation design to establish an MTD and recommended Phase 2 dose (RP2D). Safety assessed through the monitoring of adverse events (AEs), serious adverse events (SAEs), clinical laboratory parameters (hematology and serum chemistry), vital sign measurements, electrocardiograms (ECGs) and physical examinations.
Time frame: Up to 6 weeks for each dose cohort
Population: Full analysis set (FAS): All subjects who were administered any fraction of a dose of study medication
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Participants | Maximum Tolerated Dose (MTD) of E6201 | 320 E6201 MTD (mg/m^2) IV twice weekly |
Primary
Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)
A DLT was defined as any one of the following events: prolonged myelosuppression (as defined by the National Cancer Institute \[NCI\] criteria specific for leukemia, i.e., marrow cellularity \< 5% at ≥ 6 weeks from start of therapy without evidence of leukemia); ≥ Grade 3 non-hematologic toxicity (excluding Grade 3 nausea, vomiting or diarrhea that is adequately controlled with supportive care and resolves to ≤ Grade 2 within 48 hours, or Grade 3 electrolyte disturbances responsive to correction within 24 hours); ≥ Grade 3 liver function tests (LFTs) lasting \> 7 days; treatment interruption \> 14 days due to toxicity; or other important medical event. DLTs were collected to determine the MTD which is defined as the dose level below the dose at which ≥ 2 of 6 patients in a dose cohort experienced a DLT.
Time frame: Up to 6 weeks for each dose cohort
Population: Full analysis set (FAS): All subjects who were administered any fraction of a dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Participants | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 1 Number of Participants with DLTs |
| E6201 320 mg/m^2 Weekly | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 1 Number of Participants with DLTs |
| E6201 160 mg/m^2 Twice Weekly | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 0 Number of Participants with DLTs |
| E6201 240 mg/m^2 Twice Weekly | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 0 Number of Participants with DLTs |
| E6201 320 mg/m^2 IV Twice Weekly | Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) | 0 Number of Participants with DLTs |
Secondary
Duration of Response
Length of time from the first evidence of objective response to the first evidence of progression
Time frame: At the end of C1 and every 2 cycles thereafter through 6 months following last dose of study drug
Population: The analysis population was the per-protocol set (PPS). The PPS included all subjects in the FAS who had a valid baseline and one or more post-treatment assessments for a specified measure.~No objective responses were observed. Therefore, duration of response could not be calculated.
Secondary
Number of Participants With Suppression of in pERK by PIA 24 Hours Post-dose
Blood assay: Plasma inhibitory assay (PIA) measuring pERK in blood at 24 hours post-dose
Time frame: Cycle 1 Day 1, 24 hours post-dose.
Population: All subjects in the FAS who completed at least 1 PD assessment. Data obtained were not quantitative.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| All Participants | Number of Participants With Suppression of in pERK by PIA 24 Hours Post-dose | 1 Participants |
| E6201 320 mg/m^2 Weekly | Number of Participants With Suppression of in pERK by PIA 24 Hours Post-dose | 2 Participants |
| E6201 160 mg/m^2 Twice Weekly | Number of Participants With Suppression of in pERK by PIA 24 Hours Post-dose | 1 Participants |
| E6201 240 mg/m^2 Twice Weekly | Number of Participants With Suppression of in pERK by PIA 24 Hours Post-dose | 0 Participants |
| E6201 320 mg/m^2 IV Twice Weekly | Number of Participants With Suppression of in pERK by PIA 24 Hours Post-dose | 1 Participants |
Secondary
Number of Participants With Suppression of pAKT at 24 Hours Post-dose
phospho-AKT (pAKT) in blood assessed by Western blot at 24 hours post-dose
Time frame: Cycle 1 Day 1, 24 hours post-dose.
Population: All subjects in the FAS who completed at least 1 PD assessment. Data obtained were not quantitative.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| All Participants | Number of Participants With Suppression of pAKT at 24 Hours Post-dose | 0 Participants |
| E6201 320 mg/m^2 Weekly | Number of Participants With Suppression of pAKT at 24 Hours Post-dose | 0 Participants |
| E6201 160 mg/m^2 Twice Weekly | Number of Participants With Suppression of pAKT at 24 Hours Post-dose | 0 Participants |
| E6201 240 mg/m^2 Twice Weekly | Number of Participants With Suppression of pAKT at 24 Hours Post-dose | 0 Participants |
| E6201 320 mg/m^2 IV Twice Weekly | Number of Participants With Suppression of pAKT at 24 Hours Post-dose | 0 Participants |
Secondary
Number of Participants With Suppression of pAKT at 4 Hours Post-dose
phospho-AKT (pAKT) in blood assessed by Western blot at 4 hours post-dose
Time frame: Cycle 1 Day 1, 4 hours post-dose.
Population: All subjects in the FAS who completed at least 1 PD assessment. Data obtained were not quantitative.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| All Participants | Number of Participants With Suppression of pAKT at 4 Hours Post-dose | 0 Participants |
| E6201 320 mg/m^2 Weekly | Number of Participants With Suppression of pAKT at 4 Hours Post-dose | 0 Participants |
| E6201 160 mg/m^2 Twice Weekly | Number of Participants With Suppression of pAKT at 4 Hours Post-dose | 0 Participants |
| E6201 240 mg/m^2 Twice Weekly | Number of Participants With Suppression of pAKT at 4 Hours Post-dose | 0 Participants |
| E6201 320 mg/m^2 IV Twice Weekly | Number of Participants With Suppression of pAKT at 4 Hours Post-dose | 0 Participants |
Secondary
Number of Participants With Suppression of pERK at 24 Hours Post-dose
Measurement of phospho-ERK (pERK) in blood assessed by Western blot at 24 hours post-dose
Time frame: Cycle 1 Day 1, 24 hours post-dose.
Population: All subjects in the FAS who completed at least 1 PD assessment. Data obtained were not quantitative.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| All Participants | Number of Participants With Suppression of pERK at 24 Hours Post-dose | 2 Participants |
| E6201 320 mg/m^2 Weekly | Number of Participants With Suppression of pERK at 24 Hours Post-dose | 1 Participants |
| E6201 160 mg/m^2 Twice Weekly | Number of Participants With Suppression of pERK at 24 Hours Post-dose | 2 Participants |
| E6201 240 mg/m^2 Twice Weekly | Number of Participants With Suppression of pERK at 24 Hours Post-dose | 1 Participants |
| E6201 320 mg/m^2 IV Twice Weekly | Number of Participants With Suppression of pERK at 24 Hours Post-dose | 0 Participants |
Secondary
Number of Participants With Suppression of pERK at 4 Hours Post-dose
phospho-ERK (pERK) in blood assessed by Western blot at 4 hours post-dose
Time frame: Cycle 1 Day 1, 4 hours post-dose.
Population: All subjects in the FAS who completed at least 1 PD assessment. Data obtained were not quantitative.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| All Participants | Number of Participants With Suppression of pERK at 4 Hours Post-dose | 3 Participants |
| E6201 320 mg/m^2 Weekly | Number of Participants With Suppression of pERK at 4 Hours Post-dose | 2 Participants |
| E6201 160 mg/m^2 Twice Weekly | Number of Participants With Suppression of pERK at 4 Hours Post-dose | 2 Participants |
| E6201 240 mg/m^2 Twice Weekly | Number of Participants With Suppression of pERK at 4 Hours Post-dose | 2 Participants |
| E6201 320 mg/m^2 IV Twice Weekly | Number of Participants With Suppression of pERK at 4 Hours Post-dose | 1 Participants |
Secondary
Number of Participants With Suppression of pERK by PIA at 4 Hours Post-dose
Blood assay: Plasma inhibitory assay (PIA) measuring pERK in blood at 4 hours post-dose
Time frame: Cycle 1 Day 1, 4 hours post-dose.
Population: All subjects in the FAS who completed at least 1 PD assessment. Data obtained were not quantitative.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| All Participants | Number of Participants With Suppression of pERK by PIA at 4 Hours Post-dose | 7 Participants |
| E6201 320 mg/m^2 Weekly | Number of Participants With Suppression of pERK by PIA at 4 Hours Post-dose | 5 Participants |
| E6201 160 mg/m^2 Twice Weekly | Number of Participants With Suppression of pERK by PIA at 4 Hours Post-dose | 2 Participants |
| E6201 240 mg/m^2 Twice Weekly | Number of Participants With Suppression of pERK by PIA at 4 Hours Post-dose | 3 Participants |
| E6201 320 mg/m^2 IV Twice Weekly | Number of Participants With Suppression of pERK by PIA at 4 Hours Post-dose | 2 Participants |
Secondary
Number of Participants With Suppression of pFLT3 at 24 Hours Post-dose
phospho-FLT3 (pFLT3) in blood assessed by Western blot at 24 hours post-dose
Time frame: Cycle 1 Day 1, 24 hours post-dose.
Population: All subjects in the FAS who completed at least 1 PD assessment. Data obtained were not quantitative.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| All Participants | Number of Participants With Suppression of pFLT3 at 24 Hours Post-dose | 0 Participants |
| E6201 320 mg/m^2 Weekly | Number of Participants With Suppression of pFLT3 at 24 Hours Post-dose | 1 Participants |
| E6201 160 mg/m^2 Twice Weekly | Number of Participants With Suppression of pFLT3 at 24 Hours Post-dose | 1 Participants |
| E6201 240 mg/m^2 Twice Weekly | Number of Participants With Suppression of pFLT3 at 24 Hours Post-dose | 1 Participants |
| E6201 320 mg/m^2 IV Twice Weekly | Number of Participants With Suppression of pFLT3 at 24 Hours Post-dose | 0 Participants |
Secondary
Number of Participants With Suppression of pFLT3 at 4 Hours Post-dose
phospho-FLT3 (pFLT3) in blood assessed by Western blot at 4 hours post-dose
Time frame: Cycle 1 Day 1, 4 hours post-dose.
Population: All subjects in the FAS who completed at least 1 PD assessment. Data obtained were not quantitative.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| All Participants | Number of Participants With Suppression of pFLT3 at 4 Hours Post-dose | 3 Participants |
| E6201 320 mg/m^2 Weekly | Number of Participants With Suppression of pFLT3 at 4 Hours Post-dose | 1 Participants |
| E6201 160 mg/m^2 Twice Weekly | Number of Participants With Suppression of pFLT3 at 4 Hours Post-dose | 1 Participants |
| E6201 240 mg/m^2 Twice Weekly | Number of Participants With Suppression of pFLT3 at 4 Hours Post-dose | 2 Participants |
| E6201 320 mg/m^2 IV Twice Weekly | Number of Participants With Suppression of pFLT3 at 4 Hours Post-dose | 0 Participants |
Secondary
Number of Participants With Suppression of pFLT3 by PIA at 24 Hours Post-dose
Blood assay: Plasma inhibitory assay (PIA) measuring pFLT3 in blood at 24 hours post-dose
Time frame: Cycle 1 Day 1, 24 hours post-dose.
Population: All subjects in the FAS who completed at least 1 PD assessment. Data obtained were not quantitative.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| All Participants | Number of Participants With Suppression of pFLT3 by PIA at 24 Hours Post-dose | 1 Participants |
| E6201 320 mg/m^2 Weekly | Number of Participants With Suppression of pFLT3 by PIA at 24 Hours Post-dose | 2 Participants |
| E6201 160 mg/m^2 Twice Weekly | Number of Participants With Suppression of pFLT3 by PIA at 24 Hours Post-dose | 1 Participants |
| E6201 240 mg/m^2 Twice Weekly | Number of Participants With Suppression of pFLT3 by PIA at 24 Hours Post-dose | 0 Participants |
| E6201 320 mg/m^2 IV Twice Weekly | Number of Participants With Suppression of pFLT3 by PIA at 24 Hours Post-dose | 1 Participants |
Secondary
Number of Participants With Suppression of pFLT3 by PIA at 4 Hours Post-dose
Blood assay: Plasma inhibitory assay (PIA) measuring pFLT3 in blood at 4 hours post-dose
Time frame: Cycle 1 Day 1, 4 hours post-dose.
Population: All subjects in the FAS who completed at least 1 PD assessment. Data obtained were not quantitative.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| All Participants | Number of Participants With Suppression of pFLT3 by PIA at 4 Hours Post-dose | 6 Participants |
| E6201 320 mg/m^2 Weekly | Number of Participants With Suppression of pFLT3 by PIA at 4 Hours Post-dose | 5 Participants |
| E6201 160 mg/m^2 Twice Weekly | Number of Participants With Suppression of pFLT3 by PIA at 4 Hours Post-dose | 2 Participants |
| E6201 240 mg/m^2 Twice Weekly | Number of Participants With Suppression of pFLT3 by PIA at 4 Hours Post-dose | 3 Participants |
| E6201 320 mg/m^2 IV Twice Weekly | Number of Participants With Suppression of pFLT3 by PIA at 4 Hours Post-dose | 2 Participants |
Secondary
Overall Response Rate
For acute myeloid leukemia (AML): Revised Recommendations of the International Working Group (IWG) Response Criteria for AML: CR: Free of leukemia-related symptoms, absolute neutrophil count (ANC) \> 1.0 x 10\^9/L, platelet count ≥ 100 x 10\^9/L, normal bone marrow with \< 5% blasts and no Auer rods. CRi: As per CR but w/ residual thrombocytopenia (platelet count \<100 x 10\^9/L) or residual neutropenia (ANC \<1.0 x 10\^9/L). PR: ≥50% decrease bone marrow blasts to 5 - 25% abnormal cells, or CR w/ ≤ 5% blasts if Auer rods present. For myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML): Modified IWG Response Criteria for MDS: CR: Free of leukemia-related symptoms, ANC ≥1.0 x 10\^9/L, platelet count ≥100 x 10\^9/L, bone marrow ≤5% myeloblasts, normal maturation of all cell lines, hemoglobin ≥ 11g/dL, no blasts in the peripheral blood. PR: All CR criteria w/ ≥50% decrease in bone marrow blasts over pre-treatment, but still \> 5%.
Time frame: At the end of C1 and every 2 cycles thereafter through 6 months following last dose of study drug
Population: The analysis population was the per-protocol set (PPS). The PPS included all subjects in the FAS who had a valid baseline and one or more post-treatment assessments for a specified measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Participants | Overall Response Rate | 0 Objective Responses |
| E6201 320 mg/m^2 Weekly | Overall Response Rate | 0 Objective Responses |
| E6201 160 mg/m^2 Twice Weekly | Overall Response Rate | 0 Objective Responses |
| E6201 240 mg/m^2 Twice Weekly | Overall Response Rate | 0 Objective Responses |
| E6201 320 mg/m^2 IV Twice Weekly | Overall Response Rate | 0 Objective Responses |
Secondary
Overall Survival
Length of time from the date of first administration of study drug to the date of death from any cause
Time frame: From C1D1 until death or study closure, up to 26 months
Population: The analysis population was the per-protocol set (PPS). The PPS included all subjects in the FAS who had a valid baseline and one or more post-treatment assessments for a specified endpoint.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| All Participants | Overall Survival | 31 Days | Standard Deviation 13.01 |
| E6201 320 mg/m^2 Weekly | Overall Survival | 68 Days | Standard Deviation 50.39 |
| E6201 160 mg/m^2 Twice Weekly | Overall Survival | 96 Days | Standard Deviation 69.3 |
| E6201 240 mg/m^2 Twice Weekly | Overall Survival | 99 Days | Standard Deviation 48.08 |
| E6201 320 mg/m^2 IV Twice Weekly | Overall Survival | 30 Days | Standard Deviation 35.37 |
Secondary
Pharmacokinetic Profile of E6201 in Plasma: AUCI
AUCI: The area under the concentration versus time curve from time 0 to infinity
Time frame: Assessed at Cycle 1 Days 1 and 15, Cycle 2 Day 1, pre-dose, 5 minutes following the end of the 2-hour infusion, 2, 4, 8 and 24 hours post-infusion. Summary PK parameters for Cycle 1 Day 1 reported.
Population: All subjects in the FAS who completed at least 1 pharmacokinetic (PK) assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Participants | Pharmacokinetic Profile of E6201 in Plasma: AUCI | 3871.83 h.ng/mL | Standard Deviation 21.7 |
| E6201 320 mg/m^2 Weekly | Pharmacokinetic Profile of E6201 in Plasma: AUCI | 2506.90 h.ng/mL | Standard Deviation 56 |
| E6201 160 mg/m^2 Twice Weekly | Pharmacokinetic Profile of E6201 in Plasma: AUCI | 1853.13 h.ng/mL | Standard Deviation 1.1 |
| E6201 240 mg/m^2 Twice Weekly | Pharmacokinetic Profile of E6201 in Plasma: AUCI | 2215.63 h.ng/mL | Standard Deviation 59 |
| E6201 320 mg/m^2 IV Twice Weekly | Pharmacokinetic Profile of E6201 in Plasma: AUCI | 6388.31 h.ng/mL | Standard Deviation 25 |
Secondary
Pharmacokinetic Profile of E6201 in Plasma: AUCT
Area under the plasma concentration versus time curve (AUC) to the last measurable concentration over the sampling time-interval.
Time frame: Assessed at Cycle 1 Days 1 and 15, Cycle 2 Day 1, pre-dose, 5 minutes following the end of the 2-hour infusion, 2, 4, 8 and 24 hours post-infusion. Summary PK parameters for Cycle 1 Day 1 reported.
Population: All subjects in the FAS who completed at least 1 pharmacokinetic (PK) assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Participants | Pharmacokinetic Profile of E6201 in Plasma: AUCT | 3797.76 h.ng/mL | Standard Deviation 20.6 |
| E6201 320 mg/m^2 Weekly | Pharmacokinetic Profile of E6201 in Plasma: AUCT | 8135.24 h.ng/mL | Standard Deviation 88 |
| E6201 160 mg/m^2 Twice Weekly | Pharmacokinetic Profile of E6201 in Plasma: AUCT | 3034.10 h.ng/mL | Standard Deviation 69.8 |
| E6201 240 mg/m^2 Twice Weekly | Pharmacokinetic Profile of E6201 in Plasma: AUCT | 2796.73 h.ng/mL | Standard Deviation 50.3 |
| E6201 320 mg/m^2 IV Twice Weekly | Pharmacokinetic Profile of E6201 in Plasma: AUCT | 6082.79 h.ng/mL | Standard Deviation 23 |
Secondary
Pharmacokinetic Profile of E6201 in Plasma: CLobs
Clearance observed (CLobs): Total body clearance for extravascular administration
Time frame: Assessed at Cycle 1 Days 1 and 15, Cycle 2 Day 1, pre-dose, 5 minutes following the end of the 2-hour infusion, 2, 4, 8 and 24 hours post-infusion. Summary PK parameters for Cycle 1 Day 1 reported.
Population: All subjects in the FAS who completed at least 1 pharmacokinetic (PK) assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Participants | Pharmacokinetic Profile of E6201 in Plasma: CLobs | 104.0 L/h | Standard Deviation 17.8 |
| E6201 320 mg/m^2 Weekly | Pharmacokinetic Profile of E6201 in Plasma: CLobs | 300.2 L/h | Standard Deviation 45.3 |
| E6201 160 mg/m^2 Twice Weekly | Pharmacokinetic Profile of E6201 in Plasma: CLobs | 150.68 L/h | Standard Deviation 15.3 |
| E6201 240 mg/m^2 Twice Weekly | Pharmacokinetic Profile of E6201 in Plasma: CLobs | 221.2 L/h | Standard Deviation 70.1 |
| E6201 320 mg/m^2 IV Twice Weekly | Pharmacokinetic Profile of E6201 in Plasma: CLobs | 85.7 L/h | Standard Deviation 33.1 |
Secondary
Pharmacokinetic Profile of E6201 in Plasma: Cmax
Cmax: Maximum measured plasma concentration over the collection period
Time frame: Assessed at Cycle 1 Days 1 and 15, Cycle 2 Day 1, pre-dose, 5 minutes following the end of the 2-hour infusion, 2, 4, 8 and 24 hours post-infusion. Summary PK parameters for Cycle 1 Day 1 reported.
Population: All subjects in the FAS who completed at least 1 pharmacokinetic (PK) assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Participants | Pharmacokinetic Profile of E6201 in Plasma: Cmax | 1195.04 ng/mL | Standard Deviation 10.6 |
| E6201 320 mg/m^2 Weekly | Pharmacokinetic Profile of E6201 in Plasma: Cmax | 1430.39 ng/mL | Standard Deviation 76.2 |
| E6201 160 mg/m^2 Twice Weekly | Pharmacokinetic Profile of E6201 in Plasma: Cmax | 736.87 ng/mL | Standard Deviation 50.7 |
| E6201 240 mg/m^2 Twice Weekly | Pharmacokinetic Profile of E6201 in Plasma: Cmax | 941.66 ng/mL | Standard Deviation 47.7 |
| E6201 320 mg/m^2 IV Twice Weekly | Pharmacokinetic Profile of E6201 in Plasma: Cmax | 1681.12 ng/mL | Standard Deviation 5.6 |
Secondary
Pharmacokinetic Profile of E6201 in Plasma: T1/2
T1/2: The apparent first-order elimination half-life
Time frame: Assessed at Cycle 1 Days 1 and 15, Cycle 2 Day 1, pre-dose, 5 minutes following the end of the 2-hour infusion, 2, 4, 8 and 24 hours post-infusion. Summary PK parameters for Cycle 1 Day 1 reported.
Population: All subjects in the FAS who completed at least 1 pharmacokinetic (PK) assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Participants | Pharmacokinetic Profile of E6201 in Plasma: T1/2 | 3.78 h | Standard Deviation 88 |
| E6201 320 mg/m^2 Weekly | Pharmacokinetic Profile of E6201 in Plasma: T1/2 | 2.71 h | Standard Deviation 87.5 |
| E6201 160 mg/m^2 Twice Weekly | Pharmacokinetic Profile of E6201 in Plasma: T1/2 | 3.20 h | Standard Deviation 43.6 |
| E6201 240 mg/m^2 Twice Weekly | Pharmacokinetic Profile of E6201 in Plasma: T1/2 | 1.66 h | Standard Deviation 4.5 |
| E6201 320 mg/m^2 IV Twice Weekly | Pharmacokinetic Profile of E6201 in Plasma: T1/2 | 5.01 h | Standard Deviation 71.1 |
Secondary
Pharmacokinetic Profile of E6201 in Plasma: VDobs
Measurement of apparent volume of distribution observed (VDobs)
Time frame: Assessed at Cycle 1 Days 1 and 15, Cycle 2 Day 1, pre-dose, 5 minutes following the end of the 2-hour infusion, 2, 4, 8 and 24 hours post-infusion. Summary PK parameters for Cycle 1 Day 1 reported.
Population: All subjects in the FAS who completed at least 1 pharmacokinetic (PK) assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Participants | Pharmacokinetic Profile of E6201 in Plasma: VDobs | 523.1 L | Standard Deviation 76.2 |
| E6201 320 mg/m^2 Weekly | Pharmacokinetic Profile of E6201 in Plasma: VDobs | 940.6 L | Standard Deviation 52.6 |
| E6201 160 mg/m^2 Twice Weekly | Pharmacokinetic Profile of E6201 in Plasma: VDobs | 718.56 L | Standard Deviation 57 |
| E6201 240 mg/m^2 Twice Weekly | Pharmacokinetic Profile of E6201 in Plasma: VDobs | 536.5 L | Standard Deviation 73.4 |
| E6201 320 mg/m^2 IV Twice Weekly | Pharmacokinetic Profile of E6201 in Plasma: VDobs | 523.6 L | Standard Deviation 42.4 |
Secondary
Pharmacokinetics of E6201 in Plasma: Tmax
Tmax: Time to maximum measured plasma concentration
Time frame: Assessed at Cycle 1 Days 1 and 15, Cycle 2 Day 1, pre-dose, 5 minutes following the end of the 2-hour infusion, 2, 4, 8 and 24 hours post-infusion. Summary PK parameters for Cycle 1 Day 1 reported.
Population: All subjects in the FAS who completed at least 1 pharmacokinetic (PK) assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Participants | Pharmacokinetics of E6201 in Plasma: Tmax | 2.34 h | Standard Deviation 7.5 |
| E6201 320 mg/m^2 Weekly | Pharmacokinetics of E6201 in Plasma: Tmax | 4.10 h | Standard Deviation 95.4 |
| E6201 160 mg/m^2 Twice Weekly | Pharmacokinetics of E6201 in Plasma: Tmax | 2.17 h | Standard Deviation 0.9 |
| E6201 240 mg/m^2 Twice Weekly | Pharmacokinetics of E6201 in Plasma: Tmax | 2.32 h | Standard Deviation 6.8 |
| E6201 320 mg/m^2 IV Twice Weekly | Pharmacokinetics of E6201 in Plasma: Tmax | 2.18 h | Standard Deviation 4.2 |
Secondary
Progression-Free Survival
Length of time from the date of first administration of study drug to the first evidence of disease progression or death, whichever is earlier
Time frame: From Cycle 1 Day 1 (C1D1) until death or study closure, up to 26 months
Population: The analysis population was the per-protocol set (PPS). The PPS included all subjects in the FAS who had a valid baseline and one or more post-treatment assessments for a specified measure.~For AML, MDS and CMML, progression was defined by relevant IWG criteria as failure to achieve at least a PR.~No responses; PFS could not be calculated.