Trial Outcomes & Findings for A Study Of Dacomitinib (PF-00299804) In Patients With Advanced Non-Small Cell Lung Cancer (NCT NCT01858389)
NCT ID: NCT01858389
Last Updated: 2017-07-18
Results Overview
BOR was best response from start of treatment until disease progression, according to the RECIST,v1.1. CR=disappearance of all preexisting lesions except nodal disease, with all nodal lesions decreased to normal size (short axis \<10 mm) and no appearance of new unequivocal malignant lesions. PR= ≥30% decrease from baseline of sum of diameters of all target lesions with no unequivocal progression of preexisting non-target lesions or appearance of new lesions. CR and PR were confirmed on a follow-up imaging assessment ≥4 weeks after the initial response documentation. Progression= ≥20% increase in the sum of diameters of target measurable lesions above the smallest sum observed, with a minimum absolute increase of 5 mm or unequivocal progression of pre-existing non-target lesions or appearance of any new unequivocal malignant lesions. Stable disease=not qualify for CR, PR or progression. BOR was analyzed only for participants with T790M mutation according to the primary study objective.
COMPLETED
PHASE2
41 participants
From baseline until disease progression, up to 61 weeks.
2017-07-18
Participant Flow
Of 41 participants enrolled in the study, 38 (16 with T790M mutation and 22 without T790M mutation) received study drug. Three of the enrolled participants without known T790M mutation did not receive treatment.
Participant milestones
| Measure |
Dacomitinib, 45/60 mg, With T790M Mutation
Participants with documented T790M mutation in exon 20 of epidermal growth factor receptor received dacomitinib, 45 mg, every 12 hours for 6 doses over Days 1-4 of a 1-week lead-in cycle. Following the lead-in cycle, all participants received dacomitinib, 60 mg, every 12 hours for 6 doses over Days 1-4 of each subsequent 2-week cycle. Dose could be escalated beyond 60 mg after consultation with and approval of the sponsor.
|
Dacomitinib, 45/60 mg, Without T790M Mutation
Participants with no known T790M mutation received dacomitinib, 45 mg, every 12 hours for 6 doses over Days 1-4 of a 1-week lead-in cycle. Following the lead-in cycle, all participants received dacomitinib, 60 mg, every 12 hours for 6 doses over Days 1-4 of each subsequent 2-week cycle.
|
|---|---|---|
|
Overall Study
STARTED
|
16
|
25
|
|
Overall Study
Received Treatment
|
16
|
22
|
|
Overall Study
COMPLETED
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
16
|
25
|
Reasons for withdrawal
| Measure |
Dacomitinib, 45/60 mg, With T790M Mutation
Participants with documented T790M mutation in exon 20 of epidermal growth factor receptor received dacomitinib, 45 mg, every 12 hours for 6 doses over Days 1-4 of a 1-week lead-in cycle. Following the lead-in cycle, all participants received dacomitinib, 60 mg, every 12 hours for 6 doses over Days 1-4 of each subsequent 2-week cycle. Dose could be escalated beyond 60 mg after consultation with and approval of the sponsor.
|
Dacomitinib, 45/60 mg, Without T790M Mutation
Participants with no known T790M mutation received dacomitinib, 45 mg, every 12 hours for 6 doses over Days 1-4 of a 1-week lead-in cycle. Following the lead-in cycle, all participants received dacomitinib, 60 mg, every 12 hours for 6 doses over Days 1-4 of each subsequent 2-week cycle.
|
|---|---|---|
|
Overall Study
Death
|
1
|
3
|
|
Overall Study
Study terminated by sponsor
|
0
|
2
|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
|
Overall Study
Progressive disease
|
10
|
11
|
|
Overall Study
Other
|
2
|
4
|
|
Overall Study
Adverse Event
|
3
|
1
|
|
Overall Study
Did not receive treatment
|
0
|
3
|
Baseline Characteristics
A Study Of Dacomitinib (PF-00299804) In Patients With Advanced Non-Small Cell Lung Cancer
Baseline characteristics by cohort
| Measure |
Dacomitinib, 45/60 mg, With T790M Mutation
n=16 Participants
Participants with documented T790M mutation in exon 20 of epidermal growth factor receptor received dacomitinib, 45 mg, every 12 hours for 6 doses over Days 1-4 of a 1-week lead-in cycle. Following the lead-in cycle, all participants received dacomitinib, 60 mg, every 12 hours for 6 doses over Days 1-4 of each subsequent 2-week cycle. Dose could be escalated beyond 60 mg after consultation with and approval of the sponsor.
|
Dacomitinib, 45/60 mg, Without T790M Mutation
n=22 Participants
Participants with no known T790M mutation received dacomitinib, 45 mg, every 12 hours for 6 doses over Days 1-4 of a 1-week lead-in cycle. Following the lead-in cycle, all participants received dacomitinib, 60 mg, every 12 hours for 6 doses over Days 1-4 of each subsequent 2-week cycle.
|
Total
n=38 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Customized
Younger than 18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Customized
Between 18 and 44 years
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Age, Customized
Between 45 and 64 years
|
9 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
22 Participants
n=5 Participants
|
|
Age, Customized
65 years and older
|
5 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
12 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
24 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
6 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
7 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From baseline until disease progression, up to 61 weeks.Population: All enrolled participants with T790M mutation
BOR was best response from start of treatment until disease progression, according to the RECIST,v1.1. CR=disappearance of all preexisting lesions except nodal disease, with all nodal lesions decreased to normal size (short axis \<10 mm) and no appearance of new unequivocal malignant lesions. PR= ≥30% decrease from baseline of sum of diameters of all target lesions with no unequivocal progression of preexisting non-target lesions or appearance of new lesions. CR and PR were confirmed on a follow-up imaging assessment ≥4 weeks after the initial response documentation. Progression= ≥20% increase in the sum of diameters of target measurable lesions above the smallest sum observed, with a minimum absolute increase of 5 mm or unequivocal progression of pre-existing non-target lesions or appearance of any new unequivocal malignant lesions. Stable disease=not qualify for CR, PR or progression. BOR was analyzed only for participants with T790M mutation according to the primary study objective.
Outcome measures
| Measure |
Dacomitinib, 45/60 mg, With T790M Mutation
n=16 Participants
Participants with documented T790M mutation in exon 20 of epidermal growth factor receptor received dacomitinib, 45 mg, every 12 hours for 6 doses over Days 1-4 of a 1-week lead-in cycle. Following the lead-in cycle, all participants received dacomitinib, 60 mg, every 12 hours for 6 doses over Days 1-4 of each subsequent 2-week cycle. Dose could be escalated beyond 60 mg after consultation with and approval of the sponsor.
|
Dacomitinib, 45/60 mg, Without T790M Mutation
Participants with no known T790M mutation received dacomitinib, 45 mg, every 12 hours for 6 doses over Days 1-4 of a 1-week lead-in cycle. Following the lead-in cycle, all participants received dacomitinib, 60 mg, every 12 hours for 6 doses over Days 1-4 of each subsequent 2-week cycle.
|
|---|---|---|
|
Best Overall Response (BOR) in Participants With T790M Mutation
Complete response (CR)
|
0 Participants
|
—
|
|
Best Overall Response (BOR) in Participants With T790M Mutation
Partial response (PR)
|
1 Participants
|
—
|
|
Best Overall Response (BOR) in Participants With T790M Mutation
Stable disease/no response
|
7 Participants
|
—
|
|
Best Overall Response (BOR) in Participants With T790M Mutation
Indeterminate
|
2 Participants
|
—
|
|
Best Overall Response (BOR) in Participants With T790M Mutation
Objective progression
|
6 Participants
|
—
|
PRIMARY outcome
Timeframe: From baseline to disease progression, up to 61 weeks.Population: All enrolled participants with T90M mutation
ORR was calculated as the percentage of participants with a confirmed CR or PR relative to the total number of participants enrolled. Response Evaluation Criteria in Solid Tumors (RECIST), version (v) 1.1 were used to define CR and PR. CR=disappearance of all preexisting lesions except nodal disease, with all nodal lesions decreased to normal size (short axis \<10 mm) and no appearance of new unequivocal malignant lesions. PR= ≥30% decrease from baseline of sum of diameters of all target lesions with no unequivocal progression of preexisting non-target lesions or appearance of new lesions. CR and PR were confirmed on a follow-up imaging assessment ≥4 weeks after the initial response documentation. ORR was analyzed only for participants with T790M mutation according to the primary study objective.
Outcome measures
| Measure |
Dacomitinib, 45/60 mg, With T790M Mutation
n=16 Participants
Participants with documented T790M mutation in exon 20 of epidermal growth factor receptor received dacomitinib, 45 mg, every 12 hours for 6 doses over Days 1-4 of a 1-week lead-in cycle. Following the lead-in cycle, all participants received dacomitinib, 60 mg, every 12 hours for 6 doses over Days 1-4 of each subsequent 2-week cycle. Dose could be escalated beyond 60 mg after consultation with and approval of the sponsor.
|
Dacomitinib, 45/60 mg, Without T790M Mutation
Participants with no known T790M mutation received dacomitinib, 45 mg, every 12 hours for 6 doses over Days 1-4 of a 1-week lead-in cycle. Following the lead-in cycle, all participants received dacomitinib, 60 mg, every 12 hours for 6 doses over Days 1-4 of each subsequent 2-week cycle.
|
|---|---|---|
|
Objective Response Rate (ORR) in Participants With T790M Mutation
|
6.3 Percentage of participants
Interval 0.2 to 30.2
|
—
|
SECONDARY outcome
Timeframe: From baseline to baseline to disease progression, up to 61 weeks.Population: All enrolled participants with T790M mutation
DCR was calculated as the percentage of participants with an objective response (CR or PR) or stable disease, based on the RECIST, v1.1, relative to the total number of participants enrolled in the cohort. If baseline tumor assessment was inadequate for a participant, and the participant could not be assessed for RECIST responses and had no objective status of stable disease documented at least 6 weeks after the start date and before the progression, the participant was only counted in the denominator. CR=disappearance of all preexisting lesions except nodal disease, with all nodal lesions decreased to normal size (short axis \<10 mm) and no appearance of new unequivocal malignant lesions. PR= ≥30% decrease from baseline of sum of diameters of all target lesions with no unequivocal progression of preexisting non-target lesions or appearance of new lesions. DCR was analyzed only for participants with T790M mutation according to the study objective.
Outcome measures
| Measure |
Dacomitinib, 45/60 mg, With T790M Mutation
n=16 Participants
Participants with documented T790M mutation in exon 20 of epidermal growth factor receptor received dacomitinib, 45 mg, every 12 hours for 6 doses over Days 1-4 of a 1-week lead-in cycle. Following the lead-in cycle, all participants received dacomitinib, 60 mg, every 12 hours for 6 doses over Days 1-4 of each subsequent 2-week cycle. Dose could be escalated beyond 60 mg after consultation with and approval of the sponsor.
|
Dacomitinib, 45/60 mg, Without T790M Mutation
Participants with no known T790M mutation received dacomitinib, 45 mg, every 12 hours for 6 doses over Days 1-4 of a 1-week lead-in cycle. Following the lead-in cycle, all participants received dacomitinib, 60 mg, every 12 hours for 6 doses over Days 1-4 of each subsequent 2-week cycle.
|
|---|---|---|
|
Disease Control Rate (DCR) for Participants With T790M Mutation
|
50 Percentage of participants
Interval 24.7 to 75.3
|
—
|
SECONDARY outcome
Timeframe: From baseline to date of disease progression or death, up to 61 weeks.Population: All enrolled participants with T790M mutation status who had an objective tumor response (complete or partial response)
Duration of response was defined as the time from first documentation of response (CR or PR, whichever occurred first) to the date of disease progression or to death due to any cause, whichever occurred first. CR and PR were defined using RECIST, v1.1. CR=disappearance of all preexisting lesions except nodal disease, with all nodal lesions decreased to normal size (short axis \<10 mm) and no appearance of new unequivocal malignant lesions. PR= ≥30% decrease from baseline of sum of diameters of all target lesions with no unequivocal progression of preexisting non-target lesions or appearance of new lesions. CR and PR were confirmed on a follow-up imaging assessment ≥4 weeks after the initial response documentation. DR was only calculated and summarized for the subgroup of participants with an objective tumor response in the cohort of participants with T790M mutation.
Outcome measures
| Measure |
Dacomitinib, 45/60 mg, With T790M Mutation
n=1 Participants
Participants with documented T790M mutation in exon 20 of epidermal growth factor receptor received dacomitinib, 45 mg, every 12 hours for 6 doses over Days 1-4 of a 1-week lead-in cycle. Following the lead-in cycle, all participants received dacomitinib, 60 mg, every 12 hours for 6 doses over Days 1-4 of each subsequent 2-week cycle. Dose could be escalated beyond 60 mg after consultation with and approval of the sponsor.
|
Dacomitinib, 45/60 mg, Without T790M Mutation
Participants with no known T790M mutation received dacomitinib, 45 mg, every 12 hours for 6 doses over Days 1-4 of a 1-week lead-in cycle. Following the lead-in cycle, all participants received dacomitinib, 60 mg, every 12 hours for 6 doses over Days 1-4 of each subsequent 2-week cycle.
|
|---|---|---|
|
Duration of Response in Participants With T790M Mutation
|
2.83 Months
|
—
|
SECONDARY outcome
Timeframe: From baseline to disease progression or death, up to 61 weeks.Population: All enrolled participants
Progression-free survival was defined as the time from the date of first dosing of dacomitinib to the date of disease progression by RECIST v1.1, per the investigators' assessment, or death due to any cause, whichever occurred first. Objective progression= ≥20% increase in the sum of diameters of target measurable lesions above the smallest sum observed, with a minimum absolute increase of 5 mm or unequivocal progression of pre-existing non-target lesions or appearance of any new unequivocal malignant lesions.
Outcome measures
| Measure |
Dacomitinib, 45/60 mg, With T790M Mutation
n=16 Participants
Participants with documented T790M mutation in exon 20 of epidermal growth factor receptor received dacomitinib, 45 mg, every 12 hours for 6 doses over Days 1-4 of a 1-week lead-in cycle. Following the lead-in cycle, all participants received dacomitinib, 60 mg, every 12 hours for 6 doses over Days 1-4 of each subsequent 2-week cycle. Dose could be escalated beyond 60 mg after consultation with and approval of the sponsor.
|
Dacomitinib, 45/60 mg, Without T790M Mutation
n=25 Participants
Participants with no known T790M mutation received dacomitinib, 45 mg, every 12 hours for 6 doses over Days 1-4 of a 1-week lead-in cycle. Following the lead-in cycle, all participants received dacomitinib, 60 mg, every 12 hours for 6 doses over Days 1-4 of each subsequent 2-week cycle.
|
|---|---|---|
|
Progression-free Survival
|
2.3 Months
Interval 1.4 to 4.4
|
1.6 Months
Interval 1.0 to 3.3
|
SECONDARY outcome
Timeframe: Month 4Population: All enrolled participants
Progression-free survival at 4 months was defined as the percentage of participants who were alive without disease progression at 4 months relative to all participants enrolled. Disease progression was defined by RECIST v1.1. Objective progression= ≥20% increase in the sum of diameters of target measurable lesions above the smallest sum observed, with a minimum absolute increase of 5 mm or unequivocal progression of pre-existing non-target lesions or appearance of any new unequivocal malignant lesions.
Outcome measures
| Measure |
Dacomitinib, 45/60 mg, With T790M Mutation
n=16 Participants
Participants with documented T790M mutation in exon 20 of epidermal growth factor receptor received dacomitinib, 45 mg, every 12 hours for 6 doses over Days 1-4 of a 1-week lead-in cycle. Following the lead-in cycle, all participants received dacomitinib, 60 mg, every 12 hours for 6 doses over Days 1-4 of each subsequent 2-week cycle. Dose could be escalated beyond 60 mg after consultation with and approval of the sponsor.
|
Dacomitinib, 45/60 mg, Without T790M Mutation
n=25 Participants
Participants with no known T790M mutation received dacomitinib, 45 mg, every 12 hours for 6 doses over Days 1-4 of a 1-week lead-in cycle. Following the lead-in cycle, all participants received dacomitinib, 60 mg, every 12 hours for 6 doses over Days 1-4 of each subsequent 2-week cycle.
|
|---|---|---|
|
Progression-free Survival at 4 Months
|
37.5 Percentage of participants
Interval 15.4 to 59.8
|
25.3 Percentage of participants
Interval 8.6 to 46.2
|
SECONDARY outcome
Timeframe: Pre-dose (hour 0), 2, 4, 6, 8, and 10 hours post-dose on Day 4, Cycle 0.Population: All participants who received at least 1 dose of study drug and who had at least 1 measured plasma concentration of dacomitinib or its major circulating metabolite PF 05199265.
Cmax was observed directly from data. Whole blood for pharmacokinetic analysis was collected immediately after completion of electrocardiograms, blood pressure, and pulse rate.
Outcome measures
| Measure |
Dacomitinib, 45/60 mg, With T790M Mutation
n=37 Participants
Participants with documented T790M mutation in exon 20 of epidermal growth factor receptor received dacomitinib, 45 mg, every 12 hours for 6 doses over Days 1-4 of a 1-week lead-in cycle. Following the lead-in cycle, all participants received dacomitinib, 60 mg, every 12 hours for 6 doses over Days 1-4 of each subsequent 2-week cycle. Dose could be escalated beyond 60 mg after consultation with and approval of the sponsor.
|
Dacomitinib, 45/60 mg, Without T790M Mutation
Participants with no known T790M mutation received dacomitinib, 45 mg, every 12 hours for 6 doses over Days 1-4 of a 1-week lead-in cycle. Following the lead-in cycle, all participants received dacomitinib, 60 mg, every 12 hours for 6 doses over Days 1-4 of each subsequent 2-week cycle.
|
|---|---|---|
|
Maximum Plasma Concentration (Cmax) for Dacomitinib and PF-05199265
Dacomitnib
|
96.76 ng/mL
Standard Deviation 37.510
|
—
|
|
Maximum Plasma Concentration (Cmax) for Dacomitinib and PF-05199265
PF-05199265 (Dacomitnib metabolite)
|
8.45 ng/mL
Standard Deviation 12.648
|
—
|
SECONDARY outcome
Timeframe: Pre-dose (hour 0), 2, 4, 6, 8, and 10 hours post-dose on Day 4, Cycle 0.Population: All participants who received at least 1 dose of study drug and who had at least 1 measured plasma concentration of dacomitinib or its major circulating metabolite PF 05199265.
Tmax was observed directly from data as time of first occurrence. Whole blood for pharmacokinetic analysis was collected immediately after completion of electrocardiograms, blood pressure, and pulse rate.
Outcome measures
| Measure |
Dacomitinib, 45/60 mg, With T790M Mutation
n=37 Participants
Participants with documented T790M mutation in exon 20 of epidermal growth factor receptor received dacomitinib, 45 mg, every 12 hours for 6 doses over Days 1-4 of a 1-week lead-in cycle. Following the lead-in cycle, all participants received dacomitinib, 60 mg, every 12 hours for 6 doses over Days 1-4 of each subsequent 2-week cycle. Dose could be escalated beyond 60 mg after consultation with and approval of the sponsor.
|
Dacomitinib, 45/60 mg, Without T790M Mutation
Participants with no known T790M mutation received dacomitinib, 45 mg, every 12 hours for 6 doses over Days 1-4 of a 1-week lead-in cycle. Following the lead-in cycle, all participants received dacomitinib, 60 mg, every 12 hours for 6 doses over Days 1-4 of each subsequent 2-week cycle.
|
|---|---|---|
|
Time to Maximum Plasma Concentration (Tmax) for Dacomitinib and PF-05199265
Dacomitinib
|
6.07 Hours
Interval 1.3 to 10.9
|
—
|
|
Time to Maximum Plasma Concentration (Tmax) for Dacomitinib and PF-05199265
PF-05199265
|
5.58 Hours
Interval 0.0 to 11.0
|
—
|
SECONDARY outcome
Timeframe: From Baseline to Cycle 0, Day 4Population: All participants who received all scheduled doses of dacomitinib and had all ECGs performed on Days 1-4 of Cycle 0 (n=number evaluable)
ECGs recorded on Day 1 of Cycle 0 were used as baseline. For the ECGs assessments, the following directions were followed by the ECG central laboratory: Blinding of ECG readers to treatment, time, and day identifiers. Review of ECGs from a particular participant was performed by a single reader. Prespecification of the lead for internal measurements. Baseline and on-treatment ECG assessments were based on the same lead.
Outcome measures
| Measure |
Dacomitinib, 45/60 mg, With T790M Mutation
n=32 Participants
Participants with documented T790M mutation in exon 20 of epidermal growth factor receptor received dacomitinib, 45 mg, every 12 hours for 6 doses over Days 1-4 of a 1-week lead-in cycle. Following the lead-in cycle, all participants received dacomitinib, 60 mg, every 12 hours for 6 doses over Days 1-4 of each subsequent 2-week cycle. Dose could be escalated beyond 60 mg after consultation with and approval of the sponsor.
|
Dacomitinib, 45/60 mg, Without T790M Mutation
Participants with no known T790M mutation received dacomitinib, 45 mg, every 12 hours for 6 doses over Days 1-4 of a 1-week lead-in cycle. Following the lead-in cycle, all participants received dacomitinib, 60 mg, every 12 hours for 6 doses over Days 1-4 of each subsequent 2-week cycle.
|
|---|---|---|
|
Changes From Time-matched Baseline in Adjusted Fridericia Corrected QT Interval (QTcF) on Echocardiogram (ECG)
QTcF Interval Cycle 0, Day 4: Hour 0
|
1.7 msecs
Interval -2.33 to 5.64
|
—
|
|
Changes From Time-matched Baseline in Adjusted Fridericia Corrected QT Interval (QTcF) on Echocardiogram (ECG)
QTcF Interval Cycle 0, Day 4: Hour 2
|
4.4 msecs
Interval 1.85 to 6.97
|
—
|
|
Changes From Time-matched Baseline in Adjusted Fridericia Corrected QT Interval (QTcF) on Echocardiogram (ECG)
QTcF Interval Cycle 0, Day 4: Hour 4
|
0.4 msecs
Interval -3.89 to 4.64
|
—
|
|
Changes From Time-matched Baseline in Adjusted Fridericia Corrected QT Interval (QTcF) on Echocardiogram (ECG)
QTcF Interval Cycle 0, Day 4: Hour 6 (n=31)
|
-0.4 msecs
Interval -3.98 to 3.14
|
—
|
|
Changes From Time-matched Baseline in Adjusted Fridericia Corrected QT Interval (QTcF) on Echocardiogram (ECG)
QTcF Interval Cycle 0, Day 4: Hour 8 (n=31)
|
0.1 msecs
Interval -2.43 to 2.63
|
—
|
|
Changes From Time-matched Baseline in Adjusted Fridericia Corrected QT Interval (QTcF) on Echocardiogram (ECG)
QTcF Interval Cycle 0, Day 4: Hour 10 (n=31)
|
0.5 msecs
Interval -2.58 to 3.68
|
—
|
Adverse Events
Dacomitinib, 45/60 mg, With T790M Mutation
Dacomitinib, 45/60 mg, Without T790M Mutation
Serious adverse events
| Measure |
Dacomitinib, 45/60 mg, With T790M Mutation
n=16 participants at risk
Participants with documented T790M mutation in exon 20 of epidermal growth factor receptor received dacomitinib, 45 mg, every 12 hours for 6 doses over Days 1-4 of a 1-week lead-in cycle. Following the lead-in cycle, all participants received dacomitinib, 60 mg, every 12 hours for 6 doses over Days 1-4 of each subsequent 2-week cycle. Dose could be escalated beyond 60 mg after consultation with and approval of the sponsor.
|
Dacomitinib, 45/60 mg, Without T790M Mutation
n=22 participants at risk
Participants with no known T790M mutation received dacomitinib, 45 mg, every 12 hours for 6 doses over Days 1-4 of a 1-week lead-in cycle. Following the lead-in cycle, all participants received dacomitinib, 60 mg, every 12 hours for 6 doses over Days 1-4 of each subsequent 2-week cycle.
|
|---|---|---|
|
Cardiac disorders
Cardio-respiratory arrest
|
6.2%
1/16
|
0.00%
0/22
|
|
Gastrointestinal disorders
Diarrhoea
|
6.2%
1/16
|
13.6%
3/22
|
|
Gastrointestinal disorders
Nausea
|
6.2%
1/16
|
4.5%
1/22
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.00%
0/16
|
4.5%
1/22
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/16
|
4.5%
1/22
|
|
General disorders
Chest pain
|
0.00%
0/16
|
4.5%
1/22
|
|
General disorders
Fatigue
|
0.00%
0/16
|
4.5%
1/22
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
6.2%
1/16
|
0.00%
0/22
|
|
Infections and infestations
Sepsis
|
6.2%
1/16
|
4.5%
1/22
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/16
|
4.5%
1/22
|
|
Injury, poisoning and procedural complications
Hip fracture
|
0.00%
0/16
|
4.5%
1/22
|
|
Investigations
Alanine aminotransferase increased
|
6.2%
1/16
|
0.00%
0/22
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/16
|
4.5%
1/22
|
|
Metabolism and nutrition disorders
Dehydration
|
6.2%
1/16
|
4.5%
1/22
|
|
Metabolism and nutrition disorders
Failure to thrive
|
0.00%
0/16
|
4.5%
1/22
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
6.2%
1/16
|
0.00%
0/22
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
6.2%
1/16
|
0.00%
0/22
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
6.2%
1/16
|
0.00%
0/22
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progression
|
6.2%
1/16
|
0.00%
0/22
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to central nervous system
|
6.2%
1/16
|
0.00%
0/22
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Non-small cell lung cancer
|
6.2%
1/16
|
4.5%
1/22
|
|
Psychiatric disorders
Mental status changes
|
6.2%
1/16
|
0.00%
0/22
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/16
|
9.1%
2/22
|
|
Respiratory, thoracic and mediastinal disorders
Pleuritic pain
|
6.2%
1/16
|
0.00%
0/22
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
6.2%
1/16
|
0.00%
0/22
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/16
|
4.5%
1/22
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.00%
0/16
|
4.5%
1/22
|
Other adverse events
| Measure |
Dacomitinib, 45/60 mg, With T790M Mutation
n=16 participants at risk
Participants with documented T790M mutation in exon 20 of epidermal growth factor receptor received dacomitinib, 45 mg, every 12 hours for 6 doses over Days 1-4 of a 1-week lead-in cycle. Following the lead-in cycle, all participants received dacomitinib, 60 mg, every 12 hours for 6 doses over Days 1-4 of each subsequent 2-week cycle. Dose could be escalated beyond 60 mg after consultation with and approval of the sponsor.
|
Dacomitinib, 45/60 mg, Without T790M Mutation
n=22 participants at risk
Participants with no known T790M mutation received dacomitinib, 45 mg, every 12 hours for 6 doses over Days 1-4 of a 1-week lead-in cycle. Following the lead-in cycle, all participants received dacomitinib, 60 mg, every 12 hours for 6 doses over Days 1-4 of each subsequent 2-week cycle.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
6.2%
1/16
|
4.5%
1/22
|
|
Blood and lymphatic system disorders
Leukocytosis
|
0.00%
0/16
|
4.5%
1/22
|
|
Blood and lymphatic system disorders
Lymphadenopathy
|
0.00%
0/16
|
9.1%
2/22
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/16
|
9.1%
2/22
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
6.2%
1/16
|
0.00%
0/22
|
|
Cardiac disorders
Atrial fibrillation
|
6.2%
1/16
|
0.00%
0/22
|
|
Cardiac disorders
Tachycardia
|
0.00%
0/16
|
4.5%
1/22
|
|
Ear and labyrinth disorders
Tinnitus
|
0.00%
0/16
|
4.5%
1/22
|
|
Eye disorders
Conjunctivitis allergic
|
6.2%
1/16
|
0.00%
0/22
|
|
Eye disorders
Dry eye
|
6.2%
1/16
|
4.5%
1/22
|
|
Eye disorders
Eye irritation
|
0.00%
0/16
|
4.5%
1/22
|
|
Eye disorders
Lacrimation increased
|
6.2%
1/16
|
0.00%
0/22
|
|
Eye disorders
Vision blurred
|
6.2%
1/16
|
0.00%
0/22
|
|
Gastrointestinal disorders
Abdominal distension
|
6.2%
1/16
|
4.5%
1/22
|
|
Gastrointestinal disorders
Abdominal pain
|
18.8%
3/16
|
18.2%
4/22
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/16
|
4.5%
1/22
|
|
Gastrointestinal disorders
Aphthous ulcer
|
6.2%
1/16
|
0.00%
0/22
|
|
Gastrointestinal disorders
Cheilitis
|
6.2%
1/16
|
0.00%
0/22
|
|
Gastrointestinal disorders
Constipation
|
18.8%
3/16
|
18.2%
4/22
|
|
Gastrointestinal disorders
Diarrhoea
|
87.5%
14/16
|
72.7%
16/22
|
|
Gastrointestinal disorders
Dry mouth
|
6.2%
1/16
|
4.5%
1/22
|
|
Gastrointestinal disorders
Dyspepsia
|
6.2%
1/16
|
4.5%
1/22
|
|
Gastrointestinal disorders
Dysphagia
|
6.2%
1/16
|
4.5%
1/22
|
|
Gastrointestinal disorders
Haematochezia
|
6.2%
1/16
|
0.00%
0/22
|
|
Gastrointestinal disorders
Lip disorder
|
0.00%
0/16
|
4.5%
1/22
|
|
Gastrointestinal disorders
Lip pain
|
0.00%
0/16
|
4.5%
1/22
|
|
Gastrointestinal disorders
Mouth ulceration
|
6.2%
1/16
|
0.00%
0/22
|
|
Gastrointestinal disorders
Nausea
|
43.8%
7/16
|
40.9%
9/22
|
|
Gastrointestinal disorders
Oesophagitis
|
6.2%
1/16
|
0.00%
0/22
|
|
Gastrointestinal disorders
Oral dysaesthesia
|
6.2%
1/16
|
0.00%
0/22
|
|
Gastrointestinal disorders
Oral mucosal erythema
|
6.2%
1/16
|
0.00%
0/22
|
|
Gastrointestinal disorders
Oral pain
|
12.5%
2/16
|
0.00%
0/22
|
|
Gastrointestinal disorders
Proctalgia
|
0.00%
0/16
|
4.5%
1/22
|
|
Gastrointestinal disorders
Retching
|
0.00%
0/16
|
4.5%
1/22
|
|
Gastrointestinal disorders
Stomatitis
|
43.8%
7/16
|
22.7%
5/22
|
|
Gastrointestinal disorders
Vomiting
|
12.5%
2/16
|
13.6%
3/22
|
|
General disorders
Chest pain
|
6.2%
1/16
|
4.5%
1/22
|
|
General disorders
Face oedema
|
0.00%
0/16
|
4.5%
1/22
|
|
General disorders
Fatigue
|
37.5%
6/16
|
31.8%
7/22
|
|
General disorders
Gait disturbance
|
0.00%
0/16
|
4.5%
1/22
|
|
General disorders
Influenza like illness
|
6.2%
1/16
|
9.1%
2/22
|
|
General disorders
Local swelling
|
6.2%
1/16
|
0.00%
0/22
|
|
General disorders
Mass
|
6.2%
1/16
|
0.00%
0/22
|
|
General disorders
Mucosal inflammation
|
6.2%
1/16
|
13.6%
3/22
|
|
General disorders
Non-cardiac chest pain
|
6.2%
1/16
|
4.5%
1/22
|
|
General disorders
Oedema
|
6.2%
1/16
|
0.00%
0/22
|
|
General disorders
Oedema peripheral
|
6.2%
1/16
|
9.1%
2/22
|
|
General disorders
Pyrexia
|
6.2%
1/16
|
0.00%
0/22
|
|
General disorders
Ulcer haemorrhage
|
6.2%
1/16
|
0.00%
0/22
|
|
General disorders
Xerosis
|
12.5%
2/16
|
0.00%
0/22
|
|
Immune system disorders
Seasonal allergy
|
0.00%
0/16
|
4.5%
1/22
|
|
Infections and infestations
Carbuncle
|
0.00%
0/16
|
4.5%
1/22
|
|
Infections and infestations
Conjunctivitis
|
12.5%
2/16
|
4.5%
1/22
|
|
Infections and infestations
Diverticulitis
|
0.00%
0/16
|
4.5%
1/22
|
|
Infections and infestations
Ear infection fungal
|
6.2%
1/16
|
0.00%
0/22
|
|
Infections and infestations
Infection
|
0.00%
0/16
|
4.5%
1/22
|
|
Infections and infestations
Paronychia
|
25.0%
4/16
|
31.8%
7/22
|
|
Infections and infestations
Pneumonia
|
0.00%
0/16
|
4.5%
1/22
|
|
Infections and infestations
Upper respiratory tract infection
|
6.2%
1/16
|
0.00%
0/22
|
|
Injury, poisoning and procedural complications
Arthropod bite
|
0.00%
0/16
|
4.5%
1/22
|
|
Injury, poisoning and procedural complications
Contusion
|
0.00%
0/16
|
4.5%
1/22
|
|
Injury, poisoning and procedural complications
Fall
|
6.2%
1/16
|
0.00%
0/22
|
|
Injury, poisoning and procedural complications
Ligament sprain
|
0.00%
0/16
|
4.5%
1/22
|
|
Investigations
Alanine aminotransferase decreased
|
6.2%
1/16
|
0.00%
0/22
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/16
|
4.5%
1/22
|
|
Investigations
Aspartate aminotransferase increased
|
12.5%
2/16
|
4.5%
1/22
|
|
Investigations
Blood alkaline phosphatase increased
|
12.5%
2/16
|
4.5%
1/22
|
|
Investigations
Blood bicarbonate decreased
|
6.2%
1/16
|
0.00%
0/22
|
|
Investigations
Human chorionic gonadotropin increased
|
6.2%
1/16
|
0.00%
0/22
|
|
Investigations
Lymphocyte count decreased
|
6.2%
1/16
|
0.00%
0/22
|
|
Investigations
Neutrophil count decreased
|
6.2%
1/16
|
0.00%
0/22
|
|
Investigations
Weight decreased
|
6.2%
1/16
|
4.5%
1/22
|
|
Investigations
White blood cell count decreased
|
0.00%
0/16
|
4.5%
1/22
|
|
Metabolism and nutrition disorders
Decreased appetite
|
25.0%
4/16
|
22.7%
5/22
|
|
Metabolism and nutrition disorders
Dehydration
|
6.2%
1/16
|
4.5%
1/22
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
0.00%
0/16
|
4.5%
1/22
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
12.5%
2/16
|
4.5%
1/22
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
6.2%
1/16
|
4.5%
1/22
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
6.2%
1/16
|
0.00%
0/22
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
6.2%
1/16
|
0.00%
0/22
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
12.5%
2/16
|
4.5%
1/22
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
6.2%
1/16
|
0.00%
0/22
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
12.5%
2/16
|
9.1%
2/22
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
0.00%
0/16
|
4.5%
1/22
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
6.2%
1/16
|
0.00%
0/22
|
|
Musculoskeletal and connective tissue disorders
Groin pain
|
6.2%
1/16
|
0.00%
0/22
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.00%
0/16
|
4.5%
1/22
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
0.00%
0/16
|
4.5%
1/22
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.00%
0/16
|
4.5%
1/22
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
18.8%
3/16
|
4.5%
1/22
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/16
|
4.5%
1/22
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
12.5%
2/16
|
0.00%
0/22
|
|
Nervous system disorders
Dizziness
|
6.2%
1/16
|
9.1%
2/22
|
|
Nervous system disorders
Dysgeusia
|
12.5%
2/16
|
4.5%
1/22
|
|
Nervous system disorders
Headache
|
12.5%
2/16
|
13.6%
3/22
|
|
Nervous system disorders
Hypoaesthesia
|
6.2%
1/16
|
0.00%
0/22
|
|
Nervous system disorders
Neuropathy peripheral
|
12.5%
2/16
|
0.00%
0/22
|
|
Nervous system disorders
Parkinson's disease
|
0.00%
0/16
|
4.5%
1/22
|
|
Nervous system disorders
Seizure
|
0.00%
0/16
|
4.5%
1/22
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/16
|
4.5%
1/22
|
|
Psychiatric disorders
Confusional state
|
0.00%
0/16
|
4.5%
1/22
|
|
Psychiatric disorders
Delirium
|
0.00%
0/16
|
4.5%
1/22
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/16
|
9.1%
2/22
|
|
Renal and urinary disorders
Chronic kidney disease
|
0.00%
0/16
|
4.5%
1/22
|
|
Renal and urinary disorders
Dysuria
|
0.00%
0/16
|
4.5%
1/22
|
|
Renal and urinary disorders
Hydronephrosis
|
6.2%
1/16
|
0.00%
0/22
|
|
Renal and urinary disorders
Micturition urgency
|
0.00%
0/16
|
4.5%
1/22
|
|
Renal and urinary disorders
Urethral pain
|
0.00%
0/16
|
4.5%
1/22
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
12.5%
2/16
|
4.5%
1/22
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
0.00%
0/16
|
4.5%
1/22
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
12.5%
2/16
|
18.2%
4/22
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
6.2%
1/16
|
9.1%
2/22
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
18.8%
3/16
|
0.00%
0/22
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
6.2%
1/16
|
0.00%
0/22
|
|
Respiratory, thoracic and mediastinal disorders
Nasal disorder
|
0.00%
0/16
|
4.5%
1/22
|
|
Respiratory, thoracic and mediastinal disorders
Nasal inflammation
|
6.2%
1/16
|
0.00%
0/22
|
|
Respiratory, thoracic and mediastinal disorders
Nasal ulcer
|
6.2%
1/16
|
0.00%
0/22
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/16
|
4.5%
1/22
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/16
|
4.5%
1/22
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
0.00%
0/16
|
4.5%
1/22
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
0.00%
0/16
|
4.5%
1/22
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
6.2%
1/16
|
9.1%
2/22
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
6.2%
1/16
|
4.5%
1/22
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
6.2%
1/16
|
0.00%
0/22
|
|
Skin and subcutaneous tissue disorders
Dermatitis acneiform
|
25.0%
4/16
|
13.6%
3/22
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
43.8%
7/16
|
31.8%
7/22
|
|
Skin and subcutaneous tissue disorders
Eczema
|
6.2%
1/16
|
0.00%
0/22
|
|
Skin and subcutaneous tissue disorders
Erythema
|
6.2%
1/16
|
9.1%
2/22
|
|
Skin and subcutaneous tissue disorders
Hair texture abnormal
|
6.2%
1/16
|
0.00%
0/22
|
|
Skin and subcutaneous tissue disorders
Nail discolouration
|
0.00%
0/16
|
4.5%
1/22
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
0.00%
0/16
|
4.5%
1/22
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
6.2%
1/16
|
22.7%
5/22
|
|
Skin and subcutaneous tissue disorders
Rash
|
50.0%
8/16
|
54.5%
12/22
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
12.5%
2/16
|
4.5%
1/22
|
|
Skin and subcutaneous tissue disorders
Skin fissures
|
12.5%
2/16
|
0.00%
0/22
|
|
Skin and subcutaneous tissue disorders
Skin irritation
|
12.5%
2/16
|
0.00%
0/22
|
|
Skin and subcutaneous tissue disorders
Skin ulcer
|
6.2%
1/16
|
4.5%
1/22
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
0.00%
0/16
|
4.5%
1/22
|
|
Vascular disorders
Deep vein thrombosis
|
0.00%
0/16
|
4.5%
1/22
|
|
Vascular disorders
Hypertension
|
6.2%
1/16
|
0.00%
0/22
|
|
Vascular disorders
Lymphoedema
|
0.00%
0/16
|
4.5%
1/22
|
Additional Information
Pfizer ClinicalTrials.gov Call Center
Pfizer, Inc.
Results disclosure agreements
- Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
- Publication restrictions are in place
Restriction type: OTHER