E6201 Part A (Dose Escalation): Intravenous (IV) infusion administered over 30 minutes once weekly for 3 weeks (Days 1, 8, and 15). The first 3 to 6 subjects of the first cohort will receive 20 mg/m\^2/week for a cycle of 3 weeks followed by a 1-week rest period. Subsequent dose escalations may increase at increments of 100% until two Grade 2 toxicities or 1 dose-limiting toxicity (DLT) are observed in a dose group. Thereafter, doses will be increased in increments of 50% or less until the maximum tolerated dose (MTD) is determined. Part B (MTD Expansion): After the MTD is determined in Part A, 15 additional subjects will continue to receive cycles at the MTD.

E6201

Eisai Medical Services

The purpose of this study is to determine the maximum tolerated dose (MTD), safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary anti-tumor activity of E6201 in subjects with advanced solid tumors.

A Phase 1, Multicenter, Open-Label, Dose-Escalation, Safety, Pharmacokinetic, and Pharmacodynamic Study of E6201 in Subjects With Advanced Solid Tumors

Eisai Inc.

Neoplasms

Symptoms and General Pathology

All Conditions

Skin and Connective Tissue Diseases

Nervous System Diseases

Rare Diseases

Neoplasm Metastasis

Melanoma

Brain Neoplasms

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neoplastic Processes

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Dabrafenib

Protein Kinase Inhibitors

Enzyme Inhibitors

E6201 320 mg/m\^2 administered IV over 2 hours twice weekly on Days 1, 4, 8, 11, 15 and 18, repeated every 28 days (=1 cycle).

Dose reductions for toxicity are 240 mg/m\^2 (Dose Level -1) and 160 mg/m\^2 (Dose Level -2) twice weekly.

Dose Level 1: E6201 320 mg/m\^2 twice weekly plus dabrafenib 150 mg BID. Dose Level -1: E6201 240 mg/m\^2 twice weekly plus dabrafenib 150 mg BID. Dose Level -2: E6201 240 mg/m\^2 twice weekly plus dabrafenib 100 mg BID. Dose Level -3: E6201 160 mg/m\^2 twice weekly plus dabrafenib 100 mg BID Dose Level -4: E6201 160 mg/m\^2 twice weekly plus dabrafenib 75 mg BID. Dose Level -5: E6201 160 mg/m\^2 twice weekly plus dabrafenib 50 mg BID.

A total of up to N=18 will be treated at the E6201 plus dabrafenib combined MTD.

E6201 formulated in cyclodextrin for IV administration.

E6201 formulated in cyclodextrin for IV administration. Dabrafenib capsules for oral administration.

E6201 plus dabrafenib

Hani M Babiker, MD

This is a Phase 1 study of E6201 plus dabrafenib for the treatment of CNS metastases in BRAF V600-mutated metastatic melanoma. A total of up to N=28-34 subjects with melanoma metastasized to the CNS will be included.

Selected subjects will be: both males and females age ≥18 years; histologically confirmed melanoma with BRAF V600 mutation with CNS metastasis; archived tumor sample from the primary, recurrent or metastatic disease with documented BRAF mutation; recovered from all acute toxicities (≤ Grade 1) due to prior immunotherapy; determined to have adequate renal and hepatic function, and no known history of significant cardiac disease.

Monotherapy Safety Run-in Phase: Following screening, a total of up to 4 subjects were enrolled. E6201 was administered by intravenous (IV) infusion over a 2-hour period at a dose of 320 mg/m\^2 twice weekly (Days 1, 4, 8, 11, 15 and 18) for three weeks, repeated every 28 days (1 cycle) until progression of disease, observation of unacceptable adverse events, intercurrent illness or changes in the subject's condition that prevents further study participation.

Combination Safety Run-in Phase: Following screening, a total of 6-12 subjects are anticipated to establish the recommended doses of E6201 plus dabrafenib. E6201 will be administered by IV infusion over a 2-hour period twice weekly (Days 1, 4, 8, 11, 15 and 18) repeated every 28 days plus dabrafenib orally twice daily (=1 cycle).

Dose Level 1: E6201 320 mg/m\^2 twice weekly plus dabrafenib 150 mg BID. Dose Level -1: E6201 240 mg/m\^2 twice weekly plus dabrafenib 150 mg BID. Dose Level -2: E6201 240 mg/m\^2 twice weekly plus dabrafenib 100 mg BID. Dose Level -3: E6201 160 mg/m\^2 twice weekly plus dabrafenib 100 mg BID Dose Level -4: E6201 160 mg/m\^2 twice weekly plus dabrafenib 75 mg BID. Dose Level -5: E6201 160 mg/m\^2 twice weekly plus dabrafenib 50 mg BID.

A total of 6 subjects will be treated at the combined MTD doses for both drugs in the Combination Safety Run-in Phase before beginning the Expansion Phase.

Expansion Phase: An additional cohort of up to N=18 subjects will be treated at the E6201 plus dabrafenib combined MTD. Subjects treated at the MTD in the Combination Safety Run-in Phase will count towards accrual in the Expansion Phase.

CNS disease response will be assessed according to 2 methodologies: Response Evaluation Criteria in Solid Tumors (RECIST v. 1.1) and Response Assessment in Neuro-Oncology - Brain Metastases (RANO-BM). Non-CNS systemic disease will be assessed according to RECIST v. 1.1.

Blood for hematology and serum chemistry determinations will be collected and ECGs will be taken during the study. Assessments will be obtained at Week 8 and every 8 weeks thereafter until documented progression of disease (PD). Subjects who demonstrate clinical benefit will be allowed to continue therapy with E6201 until progression of disease, observation of unacceptable adverse events, intercurrent illness or changes in the subject's condition that prevents further study participation.

4 subjects were treated in the E6201 Monotherapy Safety Run-in Phase. A total of 6-12 subjects are anticipated in the E6201 plus dabrafenib Combination Safety Run-in Phase. Once an MTD of the combination is determined, a total of 6 subjects will be treated at the combined MTD before the Expansion Phase will begin. In the Expansion Phase, an additional cohort of up to N=18 subjects will be treated at the combined E6201 plus dabrafenib MTD. Subjects treated at the MTD in the Combination Safety Run-in Phase will count towards accrual in the Expansion Phase.

E6201 Plus Dabrafenib for the Treatment of Metastatic Melanoma Central Nervous System Metastases (CNS)

A Phase 1 Study of E6201 Plus Dabrafenib for the Treatment of Central Nervous System Metastases (CNS) From BRAF V600-Mutated Metastatic Melanoma

CNS disease response will be assessed by Response Assessment in Neuro-Oncology - Brain Metastases (RANO-BM)

CNS disease response will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

Length of time from the first evidence of Objective Response (complete response or partial response) to the first evidence of progression

Systemic disease response will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1RECIST 1.1.

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

Length of time from the date of first administration of study drug to the date of death from any cause

University of Arizona

Spirita Oncology, LLC

Adverse events were reported for all study participants who were administered at least one dose of study medication.

E6201 320 mg/m\^2 administered IV over 2 hours twice weekly on Days 1, 4, 8, 11, 15 and 18, repeated every 28 days (=1 cycle).

Dose reductions for toxicity are 240 mg/m\^2 (Dose Level -1) and 160 mg/m\^2 (Dose Level -2) twice weekly.

E6201: E6201 for Injection formulated in cyclodextrin for IV administration

Monotherapy Safety Run-in: E6201

Dose Level 1: E6201 320 mg/m\^2 twice weekly plus dabrafenib 150 mg BID. Dose Level -1: E6201 240 mg/m\^2 twice weekly plus dabrafenib 150 mg BID. Dose Level -2: E6201 240 mg/m\^2 twice weekly plus dabrafenib 100 mg BID. Dose Level -3: E6201 160 mg/m\^2 twice weekly plus dabrafenib 100 mg BID Dose Level -4: E6201 160 mg/m\^2 twice weekly plus dabrafenib 75 mg BID. Dose Level -5: E6201 160 mg/m\^2 twice weekly plus dabrafenib 50 mg BID.

E6201 plus dabrafenib: E6201 for Injection formulated in cyclodextrin for IV administration plus oral dabrafenib capsules

Combination Safety Run-in: E6201 Plus Dabrafenib

A total of up to N=18 will be treated at the E6201 plus dabrafenib combined MTD.

E6201 plus dabrafenib: E6201 for Injection formulated in cyclodextrin for IV administration plus oral dabrafenib capsules

Expansion: E6201 Plus Dabrafenib

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

ECOG Performance Status:

0 = Fully active, able to carry on all pre-disease performance without restriction

1. = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work

   = Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours
2. = Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours

Eastern Cooperative Group (ECOG) Performance Status

Prior Cancer Therapies

No subjects were enrolled in the Combination Safety Run-In or Expansion Phases of the study.

Due to the departure of the study PI from the institution, the study was terminated early.

Chief Development Officer

The analysis population was the per-protocol set (PPS). The PPS included all participants in the full analysis set (FAS) who had a valid baseline and one or more post-treatment assessments for a specific measure. No participants were enrolled in the Combination Safety Run-In or Expansion Phases of the study.

Intracranial Disease Overall Response Rate by RANO-BM

The analysis population was the per-protocol set (PPS). The PPS included all participants in the full analysis set (FAS) who had a valid baseline and one or more post-treatment assessments for a specific measure. No participants were enrolled in the Combination Safety Run-In or Expansion phases of the study.

Intracranial Disease Overall Response Rate by RECIST 1.1

There were no Objective Responses during the study. Thus, Duration of Response could not be calculated.

Intracranial Disease Duration of Response

The analysis population was the per-protocol set (PPS). The PPS included all participants in the full analysis set (FAS) who had a valid baseline and one or more post-treatment assessments for a specific measure. No subjects were enrolled in the Combination Safety Run-In or Expansion Phases of the study.

Systemic Disease Overall Response Rate (Other Than in the CNS)

Progression-Free Survival

Overall Survival

Overall Study

Blood and Lymph Conditions

Syndrome

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Preleukemia

Leukemia, Myelomonocytic, Chronic

Leukemia, Myelomonocytic, Juvenile

Myelodysplastic Syndromes

Hematologic Neoplasms

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Chronic Myelomonocytic Leukemia

Juvenile Myelomonocytic Leukemia

Chronic Graft Versus Host Disease

Acute Graft Versus Host Disease

E6201 240 mg/m\^2 administered IV over 2 hours once weekly, on Days 1, 8, 15, and 22, repeated every 28 days (= 1 cycle)

E6201 320 mg/m\^2 administered IV over 2 hours once weekly, on Days 1, 8, 15, and 22, repeated every 28 days (= 1 cycle)

E6201 160 mg/m\^2 administered IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle)

E6201 240 mg/m\^2 administered IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22 and 25, repeated every 28 days (= 1 cycle)

E6201 320 mg/m\^2 administered IV over 2 hours twice weekly, on Days 1, 4, 8, 11, 15, 18, 22, and 25, repeated every 28 days (= 1 cycle)

Gautam Borthakur, MD

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.

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.

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

A Phase 1/2a Study of E6201 for the Treatment of Advanced Hematologic Malignancies With FLT3 and/or Ras Mutations, Including Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome (MDS) or Chronic Myelomonocytic Leukemia (CMML)

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.

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.

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%.

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

Cmax: Maximum measured plasma concentration over the collection period

Tmax: Time to maximum measured plasma concentration

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

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

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

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

Measurement of apparent volume of distribution observed (VDobs)

phospho-ERK (pERK) in blood assessed by Western blot at 4 hours post-dose

Measurement of phospho-ERK (pERK) in blood assessed by Western blot at 24 hours post-dose

phospho-FLT3 (pFLT3) in blood assessed by Western blot at 4 hours post-dose

phospho-FLT3 (pFLT3) in blood assessed by Western blot at 24 hours post-dose

phospho-AKT (pAKT) in blood assessed by Western blot at 4 hours post-dose

phospho-AKT (pAKT) in blood assessed by Western blot at 24 hours post-dose

Blood assay: Plasma inhibitory assay (PIA) measuring pERK in blood at 4 hours post-dose

Blood assay: Plasma inhibitory assay (PIA) measuring pERK in blood at 24 hours post-dose

Blood assay: Plasma inhibitory assay (PIA) measuring pFLT3 in blood at 4 hours post-dose

Blood assay: Plasma inhibitory assay (PIA) measuring pFLT3 in blood at 24 hours post-dose

Adverse events were reported for all study participants who were administered any fraction of a dose of study medication.

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 240 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 320 mg/m^2 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 160 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 240 mg/m^2 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.

E6201 320 mg/m^2 Twice 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.

Cohort 1: E6201 240 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.

Cohort 2: E6201 320 mg/m^2 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.

Cohort 3: E6201 160 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.

Cohort 4: E6201 240 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.

Cohort 5: E6201 320 mg/m^2 Twice Weekly

Disease Type

ECOG Performance Status:

0 = Fully active, able to carry on all pre-disease performance without restriction

1. = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work
2. = Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours
3. = Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours
4. = Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair
5. = Dead

All Prior Cancer Treatment Regimens

Prior FLT3 Inhibitor Treatment Regimens

Although E6201 exhibited an acceptable safety profile when administered at doses up to the MTD of 320 mg/m\^2 IV twice weekly, insufficient efficacy was observed during the Phase 1 portion of the study. Thus, the Phase 2a portion was not initiated.

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

All Participants

Full analysis set (FAS): All subjects who were administered any fraction of a dose of study medication

Maximum Tolerated Dose (MTD) of E6201

E6201 320 mg/m^2 IV Twice Weekly

Full analysis set (FAS): All subjects who were administered any fraction of a dose of study medication.

Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)

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.

Overall Response Rate

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.

Duration of Response

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.

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.

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

Pharmacokinetic Profile of E6201 in Plasma: Cmax

E6201 240 mg/m\^2 administered 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 administered 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 administered 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 administered 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 administered 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

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.

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.

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.

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.

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.

Pharmacokinetic Profile of E6201 in Plasma: AUCT

Pharmacokinetic Profile of E6201 in Plasma: AUCI

Pharmacokinetic Profile of E6201 in Plasma: T1/2

Pharmacokinetic Profile of E6201 in Plasma: CLobs

Pharmacokinetic Profile of E6201 in Plasma: VDobs

All subjects in the FAS who completed at least 1 PD assessment. Data obtained were not quantitative.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Phase 1, Multicenter, Open-Label, Dose-Escalation, Safety, Pharmacokinetic, and Pharmacodynamic Study of E6201 in Subjects With Advanced Solid Tumors	NCT00794781	Advanced Solid ...	E6201	18 Years -	Eisai Inc.
E6201 Plus Dabrafenib for the Treatment of Metastatic Melanoma Central Nervous System Metastases (CNS)	NCT03332589	Malignant Melan... Brain Metastase...	E6201 E6201 plus dabr...	18 Years -	Spirita Oncology, LLC
A Phase 1, Multicenter, Open-Label, Dose-Escalation, Safety, Pharmacokinetic, and Pharmacodynamic Study of E6201 in Subjects With Advanced Solid Tumors	NCT00794781	Advanced Solid ...	E6201	18 Years -	Eisai Inc.
E6201 Plus Dabrafenib for the Treatment of Metastatic Melanoma Central Nervous System Metastases (CNS)	NCT03332589	Malignant Melan... Brain Metastase...	E6201 E6201 plus dabr...	18 Years -	Spirita Oncology, LLC
A Study of E6201 for the Treatment of Advanced Hematologic Malignancies With FLT3 and/or Ras Mutations	NCT02418000	AML MDS CMML	E6201	18 Years -	Spirita Oncology, LLC
A Phase 1, Multicenter, Open-Label, Dose-Escalation, Safety, Pharmacokinetic, and Pharmacodynamic Study of E6201 in Subjects With Advanced Solid Tumors	NCT00794781	Advanced Solid ...	E6201	18 Years -	Eisai Inc.

Spots Global Cancer Trial Database for e6201

Every month we try and update this database with for e6201 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for e6201

Every month we try and update this database with for e6201 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for e6201 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.