Trial Outcomes & Findings for E6201 Plus Dabrafenib for the Treatment of Metastatic Melanoma Central Nervous System Metastases (CNS) (NCT NCT03332589)
NCT ID: NCT03332589
Last Updated: 2022-05-20
Results Overview
CNS disease response will be assessed by Response Assessment in Neuro-Oncology - Brain Metastases (RANO-BM)
Recruitment status
TERMINATED
Study phase
PHASE1
Target enrollment
4 participants
Primary outcome timeframe
At the end of Cycle 2 and every 2 cycles through 6 months following last dose of study drug (each cycle is 28 days) up to 1 year.
Results posted on
2022-05-20
Participant Flow
The study was terminated before any participants were enrolled in the Combination or Expansion Phases.
Participant milestones
| Measure |
Monotherapy Safety Run-in: E6201
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
|
Combination Safety Run-in: E6201 Plus Dabrafenib
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
|
Expansion: 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
|
|---|---|---|---|
|
Overall Study
STARTED
|
4
|
0
|
0
|
|
Overall Study
COMPLETED
|
0
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
4
|
0
|
0
|
Reasons for withdrawal
| Measure |
Monotherapy Safety Run-in: E6201
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
|
Combination Safety Run-in: E6201 Plus Dabrafenib
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
|
Expansion: 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
|
|---|---|---|---|
|
Overall Study
Lack of Efficacy
|
2
|
0
|
0
|
|
Overall Study
Adverse Event
|
1
|
0
|
0
|
|
Overall Study
Death
|
1
|
0
|
0
|
Baseline Characteristics
E6201 Plus Dabrafenib for the Treatment of Metastatic Melanoma Central Nervous System Metastases (CNS)
Baseline characteristics by cohort
| Measure |
Monotherapy Safety Run-in: E6201
n=4 Participants
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
|
Combination Safety Run-in: E6201 Plus Dabrafenib
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
|
Expansion: 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
|
Total
n=4 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
51 years
STANDARD_DEVIATION 14.7 • n=5 Participants
|
—
|
—
|
51 years
STANDARD_DEVIATION 14.7 • n=4 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
—
|
—
|
2 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
—
|
—
|
2 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
—
|
—
|
1 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
3 Participants
n=5 Participants
|
—
|
—
|
3 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
—
|
—
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
—
|
—
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
—
|
—
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
—
|
—
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
—
|
—
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
4 Participants
n=5 Participants
|
—
|
—
|
4 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
—
|
—
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
—
|
—
|
0 Participants
n=4 Participants
|
|
Region of Enrollment
United States
|
4 participants
n=5 Participants
|
—
|
—
|
4 participants
n=4 Participants
|
|
Eastern Cooperative Group (ECOG) Performance Status
0
|
1 Participants
n=5 Participants
|
—
|
—
|
1 Participants
n=4 Participants
|
|
Eastern Cooperative Group (ECOG) Performance Status
1
|
2 Participants
n=5 Participants
|
—
|
—
|
2 Participants
n=4 Participants
|
|
Eastern Cooperative Group (ECOG) Performance Status
2
|
1 Participants
n=5 Participants
|
—
|
—
|
1 Participants
n=4 Participants
|
|
Prior Cancer Therapies
|
5.5 regimens
n=5 Participants
|
—
|
—
|
5.5 regimens
n=4 Participants
|
PRIMARY outcome
Timeframe: At the end of Cycle 2 and every 2 cycles through 6 months following last dose of study drug (each cycle is 28 days) up to 1 year.Population: 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.
CNS disease response will be assessed by Response Assessment in Neuro-Oncology - Brain Metastases (RANO-BM)
Outcome measures
| Measure |
Monotherapy Safety Run-in: E6201
n=4 Participants
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
|
Combination Safety Run-in: E6201 Plus Dabrafenib
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
|
Expansion: 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
|
|---|---|---|---|
|
Intracranial Disease Overall Response Rate by RANO-BM
Complete Response
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Intracranial Disease Overall Response Rate by RANO-BM
Partial Response
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Intracranial Disease Overall Response Rate by RANO-BM
Stable Disease
|
2 Participants
|
0 Participants
|
0 Participants
|
|
Intracranial Disease Overall Response Rate by RANO-BM
Progressive Disease
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Intracranial Disease Overall Response Rate by RANO-BM
Not Evaluable
|
1 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: At the end of Cycle 2 and every 2 cycles through 6 months following last dose of study drug (each cycle is 28 days) up to 1 year.Population: 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.
CNS disease response will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
Outcome measures
| Measure |
Monotherapy Safety Run-in: E6201
n=4 Participants
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
|
Combination Safety Run-in: E6201 Plus Dabrafenib
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
|
Expansion: 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
|
|---|---|---|---|
|
Intracranial Disease Overall Response Rate by RECIST 1.1
Complete Response
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Intracranial Disease Overall Response Rate by RECIST 1.1
Partial Response
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Intracranial Disease Overall Response Rate by RECIST 1.1
Stable Disease
|
2 Participants
|
0 Participants
|
0 Participants
|
|
Intracranial Disease Overall Response Rate by RECIST 1.1
Progressive Disease
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Intracranial Disease Overall Response Rate by RECIST 1.1
Not Evaluable
|
1 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: At the end of Cycle 2 and every 2 cycles through 6 months following last dose of study drug (each cycle is 28 days) up to 1 year.Population: There were no Objective Responses during the study. Thus, Duration of Response could not be calculated.
Length of time from the first evidence of Objective Response (complete response or partial response) to the first evidence of progression
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: At the end of Cycle 2 and every 2 cycles through 6 months following last dose of study drug (each cycle is 28 days) up to 1 year.Population: 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 response will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1RECIST 1.1.
Outcome measures
| Measure |
Monotherapy Safety Run-in: E6201
n=4 Participants
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
|
Combination Safety Run-in: E6201 Plus Dabrafenib
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
|
Expansion: 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
|
|---|---|---|---|
|
Systemic Disease Overall Response Rate (Other Than in the CNS)
Complete Response
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Systemic Disease Overall Response Rate (Other Than in the CNS)
Partial Response
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Systemic Disease Overall Response Rate (Other Than in the CNS)
Stable Disease
|
3 Participants
|
0 Participants
|
0 Participants
|
|
Systemic Disease Overall Response Rate (Other Than in the CNS)
Progressive Disease
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Systemic Disease Overall Response Rate (Other Than in the CNS)
Not Evaluable
|
1 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: From Cycle 1 Day 1 through 6 months following the last dose of study drug (each cycle is 28 days) up to 1 year.Population: 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.
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
| Measure |
Monotherapy Safety Run-in: E6201
n=1 Participants
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
|
Combination Safety Run-in: E6201 Plus Dabrafenib
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
|
Expansion: 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
|
|---|---|---|---|
|
Progression-Free Survival
|
NA months
NA: Median could not be estimated due to insufficient number of participants with the event.
|
—
|
—
|
SECONDARY outcome
Timeframe: From Cycle 1 Day 1 through 6 months following the last dose of study drug or death, whichever is earlier (each cycle is 28 days) up to 1 year.Population: 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.
Length of time from the date of first administration of study drug to the date of death from any cause
Outcome measures
| Measure |
Monotherapy Safety Run-in: E6201
n=1 Participants
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
|
Combination Safety Run-in: E6201 Plus Dabrafenib
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
|
Expansion: 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
|
|---|---|---|---|
|
Overall Survival
|
NA months
NA: Median could not be estimated due to insufficient number of participants with the event.
|
—
|
—
|
Adverse Events
Monotherapy Safety Run-in: E6201
Serious events: 3 serious events
Other events: 4 other events
Deaths: 1 deaths
Combination Safety Run-in: E6201 Plus Dabrafenib
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Expansion: E6201 Plus Dabrafenib
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Monotherapy Safety Run-in: E6201
n=4 participants at risk
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
|
Combination Safety Run-in: E6201 Plus Dabrafenib
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
|
Expansion: 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
|
|---|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
25.0%
1/4 • Number of events 1 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
—
0/0 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
—
0/0 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
25.0%
1/4 • Number of events 1 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
—
0/0 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
—
0/0 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
|
Infections and infestations
Sepsis
|
25.0%
1/4 • Number of events 1 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
—
0/0 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
—
0/0 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
|
Psychiatric disorders
Confusional state
|
25.0%
1/4 • Number of events 1 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
—
0/0 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
—
0/0 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
Other adverse events
| Measure |
Monotherapy Safety Run-in: E6201
n=4 participants at risk
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
|
Combination Safety Run-in: E6201 Plus Dabrafenib
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
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Expansion: 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
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|---|---|---|---|
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Blood and lymphatic system disorders
Thrombocytopenia
|
25.0%
1/4 • Number of events 1 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
—
0/0 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
—
0/0 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
|
Cardiac disorders
Tachycardia
|
25.0%
1/4 • Number of events 1 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
—
0/0 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
—
0/0 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
|
Eye disorders
Blurred vision
|
25.0%
1/4 • Number of events 1 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
—
0/0 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
—
0/0 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
|
Gastrointestinal disorders
Abdominal distension
|
25.0%
1/4 • Number of events 1 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
—
0/0 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
—
0/0 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
|
Gastrointestinal disorders
Abdominal pain
|
25.0%
1/4 • Number of events 1 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
—
0/0 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
—
0/0 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
|
General disorders
Fatigue
|
25.0%
1/4 • Number of events 1 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
—
0/0 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
—
0/0 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
|
General disorders
Gait disturbance
|
25.0%
1/4 • Number of events 1 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
—
0/0 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
—
0/0 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
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Hepatobiliary disorders
Hyperbilirubinaemia
|
25.0%
1/4 • Number of events 1 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
—
0/0 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
—
0/0 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
|
Infections and infestations
Respiratory tract infection
|
25.0%
1/4 • Number of events 1 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
—
0/0 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
—
0/0 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
|
Infections and infestations
Rhinitis
|
25.0%
1/4 • Number of events 1 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
—
0/0 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
—
0/0 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
|
Infections and infestations
Sepsis
|
50.0%
2/4 • Number of events 2 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
—
0/0 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
—
0/0 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
75.0%
3/4 • Number of events 3 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
—
0/0 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
—
0/0 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
|
Nervous system disorders
Dizziness
|
25.0%
1/4 • Number of events 1 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
—
0/0 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
—
0/0 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
|
Nervous system disorders
Neuropathy peripheral
|
25.0%
1/4 • Number of events 1 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
—
0/0 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
—
0/0 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
|
Nervous system disorders
Seizure
|
25.0%
1/4 • Number of events 1 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
—
0/0 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
—
0/0 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
|
Nervous system disorders
Vasogenic cerebral oedema
|
25.0%
1/4 • Number of events 1 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
—
0/0 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
—
0/0 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
|
Psychiatric disorders
Confusional state
|
25.0%
1/4 • Number of events 1 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
—
0/0 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
—
0/0 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
|
Renal and urinary disorders
Urinary hesitation
|
25.0%
1/4 • Number of events 1 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
—
0/0 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
—
0/0 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
|
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis
|
25.0%
1/4 • Number of events 1 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
—
0/0 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
—
0/0 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
25.0%
1/4 • Number of events 1 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
—
0/0 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
—
0/0 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
25.0%
1/4 • Number of events 1 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
—
0/0 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
—
0/0 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
25.0%
1/4 • Number of events 1 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
—
0/0 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
—
0/0 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
|
Vascular disorders
Oedema peripheral
|
25.0%
1/4 • Number of events 1 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
—
0/0 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
|
—
0/0 • Adverse event data and all-cause mortality data were collected for each subject from C1D1 to 6 months after the last dose of study drug up to 1 year.
Adverse events were reported for all study participants who were administered at least one dose of study medication.
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Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place