Trial Outcomes & Findings for A Study of E6201 for the Treatment of Advanced Hematologic Malignancies With FLT3 and/or Ras Mutations (NCT NCT02418000)

Last Updated: 2019-03-20

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

27 participants

Primary outcome timeframe

Up to 6 weeks for each dose cohort

Results posted on

2019-03-20

Participant Flow

Participant milestones

Participant milestones
Measure	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 discontinuation of study drug, and followed for up to 6 months after the last dose.	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 discontinuation of study drug, and followed for up to 6 months after the last dose.	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 discontinuation of study drug, and followed for up to 6 months after the last dose.	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 discontinuation of study drug, and followed for up to 6 months after the last dose.	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 discontinuation of study drug, and followed for up to 6 months after the last dose.
Cohort 1: E6201 240 mg/m^2 Weekly STARTED	7	0	0	0	0
Cohort 1: E6201 240 mg/m^2 Weekly COMPLETED	0	0	0	0	0
Cohort 1: E6201 240 mg/m^2 Weekly NOT COMPLETED	7	0	0	0	0
Cohort 2: E6201 320 mg/m^2 Weekly STARTED	0	10	0	0	0
Cohort 2: E6201 320 mg/m^2 Weekly COMPLETED	0	0	0	0	0
Cohort 2: E6201 320 mg/m^2 Weekly NOT COMPLETED	0	10	0	0	0
Cohort 3: 160 mg/m^2 Twice Weekly STARTED	0	0	3	0	0
Cohort 3: 160 mg/m^2 Twice Weekly COMPLETED	0	0	0	0	0
Cohort 3: 160 mg/m^2 Twice Weekly NOT COMPLETED	0	0	3	0	0
Cohort 4: 240 mg/m^2 Twice Weekly STARTED	0	0	0	3	0
Cohort 4: 240 mg/m^2 Twice Weekly COMPLETED	0	0	0	0	0
Cohort 4: 240 mg/m^2 Twice Weekly NOT COMPLETED	0	0	0	3	0
Cohort 5: 320 mg/m^2 Twice Weekly STARTED	0	0	0	0	4
Cohort 5: 320 mg/m^2 Twice Weekly COMPLETED	0	0	0	0	0
Cohort 5: 320 mg/m^2 Twice Weekly NOT COMPLETED	0	0	0	0	4

Reasons for withdrawal

Reasons for withdrawal
Measure	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 discontinuation of study drug, and followed for up to 6 months after the last dose.	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 discontinuation of study drug, and followed for up to 6 months after the last dose.	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 discontinuation of study drug, and followed for up to 6 months after the last dose.	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 discontinuation of study drug, and followed for up to 6 months after the last dose.	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 discontinuation of study drug, and followed for up to 6 months after the last dose.
Cohort 1: E6201 240 mg/m^2 Weekly Withdrawal by Subject	2	0	0	0	0
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 2: E6201 320 mg/m^2 Weekly Withdrawal by Subject	0	1	0	0	0
Cohort 2: E6201 320 mg/m^2 Weekly Lack of Efficacy	0	9	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 Withdrawal by Subject	0	0	0	0	1
Cohort 5: 320 mg/m^2 Twice Weekly Lack of Efficacy	0	0	0	0	3

Baseline Characteristics

A Study of E6201 for the Treatment of Advanced Hematologic Malignancies With FLT3 and/or Ras Mutations

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1: E6201 240 mg/m^2 Weekly n=7 Participants 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.	Cohort 2: E6201 320 mg/m^2 Weekly n=10 Participants 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.	Cohort 3: E6201 160 mg/m^2 Twice Weekly n=3 Participants 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.	Cohort 4: E6201 240 mg/m^2 Twice Weekly n=3 Participants 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.	Cohort 5: E6201 320 mg/m^2 Twice Weekly n=4 Participants 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.	Total n=27 Participants Total of all reporting groups
Age, Continuous	61.57 years STANDARD_DEVIATION 13.97 • n=5 Participants	51.10 years STANDARD_DEVIATION 19.14 • n=7 Participants	61.33 years STANDARD_DEVIATION 11.02 • n=5 Participants	56.33 years STANDARD_DEVIATION 12.01 • n=4 Participants	56.00 years STANDARD_DEVIATION 17.64 • n=21 Participants	56.26 years STANDARD_DEVIATION 15.78 • n=10 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	4 Participants n=7 Participants	2 Participants n=5 Participants	1 Participants n=4 Participants	2 Participants n=21 Participants	14 Participants n=10 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	6 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants	2 Participants n=21 Participants	13 Participants n=10 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	3 Participants n=10 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	4 Participants n=5 Participants	8 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants	4 Participants n=21 Participants	21 Participants n=10 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	3 Participants n=10 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants	2 Participants n=10 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	4 Participants n=10 Participants
Race (NIH/OMB) White	5 Participants n=5 Participants	6 Participants n=7 Participants	3 Participants n=5 Participants	2 Participants n=4 Participants	3 Participants n=21 Participants	19 Participants n=10 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	2 Participants n=10 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants
Region of Enrollment United States	7 participants n=5 Participants	10 participants n=7 Participants	3 participants n=5 Participants	3 participants n=4 Participants	4 participants n=21 Participants	27 participants n=10 Participants
Disease Type AML	4 Participants n=5 Participants	10 Participants n=7 Participants	3 Participants n=5 Participants	3 Participants n=4 Participants	4 Participants n=21 Participants	24 Participants n=10 Participants
Disease Type MDS	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=10 Participants
Disease Type CMML	2 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	2 Participants n=10 Participants
Eastern Cooperative Group (ECOG) Performance Status 0	2 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	3 Participants n=10 Participants
Eastern Cooperative Group (ECOG) Performance Status 1	5 Participants n=5 Participants	6 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants	4 Participants n=21 Participants	20 Participants n=10 Participants
Eastern Cooperative Group (ECOG) Performance Status 2	0 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	4 Participants n=10 Participants
Eastern Cooperative Group (ECOG) Performance Status 3	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants
Eastern Cooperative Group (ECOG) Performance Status 4	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants
Prior Cancer Therapies All Prior Cancer Treatment Regimens	3 Number of treatment regimens n=5 Participants	6.5 Number of treatment regimens n=7 Participants	4 Number of treatment regimens n=5 Participants	5 Number of treatment regimens n=4 Participants	4 Number of treatment regimens n=21 Participants	5 Number of treatment regimens n=10 Participants
Prior Cancer Therapies Prior FLT3 Inhibitor Treatment Regimens	1 Number of treatment regimens n=5 Participants	1 Number of treatment regimens n=7 Participants	1 Number of treatment regimens n=5 Participants	1 Number of treatment regimens n=4 Participants	1 Number of treatment regimens n=21 Participants	1 Number of treatment regimens n=10 Participants

PRIMARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	All Participants n=27 Participants All study participants who received at least 1 dose of E6201 at 240 or 320 mg/m\^2 IV weekly, or at 160, 240 or 320 mg/m\^2 IV twice weekly	E6201 320 mg/m^2 Weekly 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 discontinuation of study drug, and followed for up to 6 months after the last dose.	E6201 160 mg/m^2 Twice Weekly 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 discontinuation of study drug, and followed for up to 6 months after the last dose.	E6201 240 mg/m^2 Twice Weekly 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 discontinuation of study drug, and followed for up to 6 months after the last dose.	E6201 320 mg/m^2 IV Twice Weekly 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 discontinuation of study drug, and followed for up to 6 months after the last dose.
Maximum Tolerated Dose (MTD) of E6201	320 E6201 MTD (mg/m^2) IV twice weekly	—	—	—	—

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	All Participants n=7 Participants All study participants who received at least 1 dose of E6201 at 240 or 320 mg/m\^2 IV weekly, or at 160, 240 or 320 mg/m\^2 IV twice weekly	E6201 320 mg/m^2 Weekly n=10 Participants 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 discontinuation of study drug, and followed for up to 6 months after the last dose.	E6201 160 mg/m^2 Twice Weekly n=3 Participants 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 discontinuation of study drug, and followed for up to 6 months after the last dose.	E6201 240 mg/m^2 Twice Weekly n=3 Participants 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 discontinuation of study drug, and followed for up to 6 months after the last dose.	E6201 320 mg/m^2 IV Twice Weekly n=4 Participants 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 discontinuation of study drug, and followed for up to 6 months after the last dose.
Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)	1 Number of Participants with DLTs	1 Number of Participants with DLTs	0 Number of Participants with DLTs	0 Number of Participants with DLTs	0 Number of Participants with DLTs

SECONDARY outcome

Timeframe: 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%.

Outcome measures

Outcome measures
Measure	All Participants n=7 Participants All study participants who received at least 1 dose of E6201 at 240 or 320 mg/m\^2 IV weekly, or at 160, 240 or 320 mg/m\^2 IV twice weekly	E6201 320 mg/m^2 Weekly n=10 Participants 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 discontinuation of study drug, and followed for up to 6 months after the last dose.	E6201 160 mg/m^2 Twice Weekly n=3 Participants 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 discontinuation of study drug, and followed for up to 6 months after the last dose.	E6201 240 mg/m^2 Twice Weekly n=3 Participants 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 discontinuation of study drug, and followed for up to 6 months after the last dose.	E6201 320 mg/m^2 IV Twice Weekly n=4 Participants 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 discontinuation of study drug, and followed for up to 6 months after the last dose.
Overall Response Rate	0 Objective Responses	0 Objective Responses	0 Objective Responses	0 Objective Responses	0 Objective Responses

SECONDARY outcome

Timeframe: 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.

Length of time from the first evidence of objective response to the first evidence of progression

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Length of time from the date of first administration of study drug to the first evidence of disease progression or death, whichever is earlier

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	All Participants n=3 Participants All study participants who received at least 1 dose of E6201 at 240 or 320 mg/m\^2 IV weekly, or at 160, 240 or 320 mg/m\^2 IV twice weekly	E6201 320 mg/m^2 Weekly n=9 Participants 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 discontinuation of study drug, and followed for up to 6 months after the last dose.	E6201 160 mg/m^2 Twice Weekly n=2 Participants 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 discontinuation of study drug, and followed for up to 6 months after the last dose.	E6201 240 mg/m^2 Twice Weekly n=2 Participants 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 discontinuation of study drug, and followed for up to 6 months after the last dose.	E6201 320 mg/m^2 IV Twice Weekly n=3 Participants 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 discontinuation of study drug, and followed for up to 6 months after the last dose.
Overall Survival	31 Days Standard Deviation 13.01	68 Days Standard Deviation 50.39	96 Days Standard Deviation 69.30	99 Days Standard Deviation 48.08	30 Days Standard Deviation 35.37

SECONDARY outcome

Timeframe: 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.

Cmax: Maximum measured plasma concentration over the collection period

Outcome measures

Outcome measures
Measure	All Participants n=7 Participants All study participants who received at least 1 dose of E6201 at 240 or 320 mg/m\^2 IV weekly, or at 160, 240 or 320 mg/m\^2 IV twice weekly	E6201 320 mg/m^2 Weekly n=10 Participants 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 discontinuation of study drug, and followed for up to 6 months after the last dose.	E6201 160 mg/m^2 Twice Weekly n=3 Participants 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 discontinuation of study drug, and followed for up to 6 months after the last dose.	E6201 240 mg/m^2 Twice Weekly n=3 Participants 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 discontinuation of study drug, and followed for up to 6 months after the last dose.	E6201 320 mg/m^2 IV Twice Weekly n=4 Participants 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 discontinuation of study drug, and followed for up to 6 months after the last dose.
Pharmacokinetic Profile of E6201 in Plasma: Cmax	1195.04 ng/mL Standard Deviation 10.6	1430.39 ng/mL Standard Deviation 76.2	736.87 ng/mL Standard Deviation 50.7	941.66 ng/mL Standard Deviation 47.7	1681.12 ng/mL Standard Deviation 5.6

SECONDARY outcome

Population: All subjects in the FAS who completed at least 1 pharmacokinetic (PK) assessment.

Tmax: Time to maximum measured plasma concentration

Outcome measures

Outcome measures
Measure	All Participants n=7 Participants All study participants who received at least 1 dose of E6201 at 240 or 320 mg/m\^2 IV weekly, or at 160, 240 or 320 mg/m\^2 IV twice weekly	E6201 320 mg/m^2 Weekly n=10 Participants 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 discontinuation of study drug, and followed for up to 6 months after the last dose.	E6201 160 mg/m^2 Twice Weekly n=3 Participants 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 discontinuation of study drug, and followed for up to 6 months after the last dose.	E6201 240 mg/m^2 Twice Weekly n=3 Participants 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 discontinuation of study drug, and followed for up to 6 months after the last dose.	E6201 320 mg/m^2 IV Twice Weekly n=4 Participants 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 discontinuation of study drug, and followed for up to 6 months after the last dose.
Pharmacokinetics of E6201 in Plasma: Tmax	2.34 h Standard Deviation 7.5	4.10 h Standard Deviation 95.4	2.17 h Standard Deviation 0.9	2.32 h Standard Deviation 6.8	2.18 h Standard Deviation 4.2

SECONDARY outcome

Population: All subjects in the FAS who completed at least 1 pharmacokinetic (PK) assessment.

Area under the plasma concentration versus time curve (AUC) to the last measurable concentration over the sampling time-interval.

Outcome measures

Outcome measures
Measure	All Participants n=7 Participants All study participants who received at least 1 dose of E6201 at 240 or 320 mg/m\^2 IV weekly, or at 160, 240 or 320 mg/m\^2 IV twice weekly	E6201 320 mg/m^2 Weekly n=10 Participants 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 discontinuation of study drug, and followed for up to 6 months after the last dose.	E6201 160 mg/m^2 Twice Weekly n=3 Participants 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 discontinuation of study drug, and followed for up to 6 months after the last dose.	E6201 240 mg/m^2 Twice Weekly n=3 Participants 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 discontinuation of study drug, and followed for up to 6 months after the last dose.	E6201 320 mg/m^2 IV Twice Weekly n=4 Participants 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 discontinuation of study drug, and followed for up to 6 months after the last dose.
Pharmacokinetic Profile of E6201 in Plasma: AUCT	3797.76 h.ng/mL Standard Deviation 20.6	8135.24 h.ng/mL Standard Deviation 88.0	3034.10 h.ng/mL Standard Deviation 69.8	2796.73 h.ng/mL Standard Deviation 50.3	6082.79 h.ng/mL Standard Deviation 23.0

SECONDARY outcome

Population: All subjects in the FAS who completed at least 1 pharmacokinetic (PK) assessment.

AUCI: The area under the concentration versus time curve from time 0 to infinity

Outcome measures

Outcome measures
Measure	All Participants n=7 Participants All study participants who received at least 1 dose of E6201 at 240 or 320 mg/m\^2 IV weekly, or at 160, 240 or 320 mg/m\^2 IV twice weekly	E6201 320 mg/m^2 Weekly n=10 Participants 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 discontinuation of study drug, and followed for up to 6 months after the last dose.	E6201 160 mg/m^2 Twice Weekly n=3 Participants 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 discontinuation of study drug, and followed for up to 6 months after the last dose.	E6201 240 mg/m^2 Twice Weekly n=3 Participants 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 discontinuation of study drug, and followed for up to 6 months after the last dose.	E6201 320 mg/m^2 IV Twice Weekly n=4 Participants 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 discontinuation of study drug, and followed for up to 6 months after the last dose.
Pharmacokinetic Profile of E6201 in Plasma: AUCI	3871.83 h.ng/mL Standard Deviation 21.7	2506.90 h.ng/mL Standard Deviation 56.0	1853.13 h.ng/mL Standard Deviation 1.1	2215.63 h.ng/mL Standard Deviation 59.0	6388.31 h.ng/mL Standard Deviation 25.0

SECONDARY outcome

Population: All subjects in the FAS who completed at least 1 pharmacokinetic (PK) assessment.

T1/2: The apparent first-order elimination half-life

Outcome measures

Outcome measures
Measure	All Participants n=7 Participants All study participants who received at least 1 dose of E6201 at 240 or 320 mg/m\^2 IV weekly, or at 160, 240 or 320 mg/m\^2 IV twice weekly	E6201 320 mg/m^2 Weekly n=10 Participants 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 discontinuation of study drug, and followed for up to 6 months after the last dose.	E6201 160 mg/m^2 Twice Weekly n=3 Participants 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 discontinuation of study drug, and followed for up to 6 months after the last dose.	E6201 240 mg/m^2 Twice Weekly n=3 Participants 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 discontinuation of study drug, and followed for up to 6 months after the last dose.	E6201 320 mg/m^2 IV Twice Weekly n=4 Participants 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 discontinuation of study drug, and followed for up to 6 months after the last dose.
Pharmacokinetic Profile of E6201 in Plasma: T1/2	3.78 h Standard Deviation 88.0	2.71 h Standard Deviation 87.5	3.20 h Standard Deviation 43.6	1.66 h Standard Deviation 4.5	5.01 h Standard Deviation 71.1

SECONDARY outcome

Population: All subjects in the FAS who completed at least 1 pharmacokinetic (PK) assessment.

Clearance observed (CLobs): Total body clearance for extravascular administration

Outcome measures

Outcome measures
Measure	All Participants n=7 Participants All study participants who received at least 1 dose of E6201 at 240 or 320 mg/m\^2 IV weekly, or at 160, 240 or 320 mg/m\^2 IV twice weekly	E6201 320 mg/m^2 Weekly n=10 Participants 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 discontinuation of study drug, and followed for up to 6 months after the last dose.	E6201 160 mg/m^2 Twice Weekly n=3 Participants 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 discontinuation of study drug, and followed for up to 6 months after the last dose.	E6201 240 mg/m^2 Twice Weekly n=3 Participants 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 discontinuation of study drug, and followed for up to 6 months after the last dose.	E6201 320 mg/m^2 IV Twice Weekly n=4 Participants 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 discontinuation of study drug, and followed for up to 6 months after the last dose.
Pharmacokinetic Profile of E6201 in Plasma: CLobs	104.0 L/h Standard Deviation 17.8	300.2 L/h Standard Deviation 45.3	150.68 L/h Standard Deviation 15.3	221.2 L/h Standard Deviation 70.1	85.7 L/h Standard Deviation 33.1

SECONDARY outcome

Population: All subjects in the FAS who completed at least 1 pharmacokinetic (PK) assessment.

Measurement of apparent volume of distribution observed (VDobs)