Trial Outcomes & Findings for Local Ablative Therapy for Treatment of Oligoprogressive, EGFR-Mutated, Non-Small Cell Lung Cancer After Treatment With Osimertinib (NCT NCT02759835)
NCT ID: NCT02759835
Last Updated: 2024-06-07
Results Overview
PFS1 = time from initiation of osimertinib to first progression of disease or clinical progression, or death any cause. Progression was evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and reported using the Kaplan Meier curve. Progressive Disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The appearance of one or more new lesions is also considered progression).
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
37 participants
Primary outcome timeframe
Cycle 1 Day 1 (each cycle is 28 days) to progression of disease, range 36-1231 days
Results posted on
2024-06-07
Participant Flow
Participant milestones
| Measure |
Tyrosine Kinase Inhibitor Naïve Epidermal Growth Factor Receptor *Mutated Non Small Cell Lung Cancer
COHORT 1: Osimertinib followed by LAT followed by osimertinib. Single daily dose of Osimertinib until progression. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation.
\*including germline T790M mutation
|
EGFR Mutated NSCLC Progressed on Prior 1st/2nd Generation EGFR TKI Therapy &Acquired T790M Mutation
Cohort 2 - Osimertinib followed by LAT followed by osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on osimertinib: surgery, radiotherapy, or radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
|
Epidermal Growth Factor Receptor Mutated Non Small Cell Lung Cancer Progressed on Osimertinib
Cohort 3 - LAT followed by Osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
|
|---|---|---|---|
|
Overall Study
STARTED
|
25
|
9
|
3
|
|
Overall Study
COMPLETED
|
25
|
9
|
3
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Local Ablative Therapy for Treatment of Oligoprogressive, EGFR-Mutated, Non-Small Cell Lung Cancer After Treatment With Osimertinib
Baseline characteristics by cohort
| Measure |
Tyrosine Kinase Inhibitor Naïve Epidermal Growth Factor Receptor *Mutated Non Small Cell Lung Cancer
n=25 Participants
COHORT 1: Osimertinib followed by LAT followed by osimertinib. Single daily dose of Osimertinib until progression. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation.
\*including germline T790M mutation
|
EGFR Mutated NSCLC Progressed on Prior 1st/2nd Generation EGFR TKI Therapy &Acquired T790M Mutation
n=9 Participants
Cohort 2 - Osimertinib followed by LAT followed by osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on osimertinib: surgery, radiotherapy, or radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
|
Epidermal Growth Factor Receptor Mutated Non Small Cell Lung Cancer Progressed on Osimertinib
n=3 Participants
Cohort 3 - LAT followed by Osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
|
Total
n=37 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
14 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
22 Participants
n=4 Participants
|
|
Age, Categorical
>=65 years
|
11 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
15 Participants
n=4 Participants
|
|
Age, Continuous
|
59.54 years
STANDARD_DEVIATION 15.03 • n=5 Participants
|
58.86 years
STANDARD_DEVIATION 11.48 • n=7 Participants
|
60.13 years
STANDARD_DEVIATION 3.91 • n=5 Participants
|
59.67 years
STANDARD_DEVIATION 13.44 • n=4 Participants
|
|
Sex: Female, Male
Female
|
17 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
27 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
10 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
23 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
33 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Asian
|
6 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
8 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Black or African American
|
8 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
9 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
16 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
|
Region of Enrollment
United States
|
25 participants
n=5 Participants
|
9 participants
n=7 Participants
|
3 participants
n=5 Participants
|
37 participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Cycle 1 Day 1 (each cycle is 28 days) to progression of disease, range 36-1231 daysPopulation: Cohort 3 is not applicable for this outcome measure because these participants enrolled in the study after getting Osimertinib at an outside institution. One participant in Cohort 1 was not evaluable.
PFS1 = time from initiation of osimertinib to first progression of disease or clinical progression, or death any cause. Progression was evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and reported using the Kaplan Meier curve. Progressive Disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The appearance of one or more new lesions is also considered progression).
Outcome measures
| Measure |
All Participants in Cohort 1
n=24 Participants
COHORT 1: Osimertinib followed by LAT followed by osimertinib. Single daily dose of Osimertinib until progression. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation.
\*including germline T790M mutation
|
All Participants in Cohort 2
n=9 Participants
Cohort 2 - Osimertinib followed by LAT followed by osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on osimertinib: surgery, radiotherapy, or radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
|
Epidermal Growth Factor Receptor Mutated Non Small Cell Lung Cancer Progressed on Osimertinib
Cohort 3 - LAT followed by Osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
|
Cohort 2: Possibly Related
Cohort 2 - Osimertinib followed by LAT followed by osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on osimertinib: surgery, radiotherapy, or radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events possibly related to LAT.
|
Cohort 2: Probably Related
Cohort 2 - Osimertinib followed by LAT followed by osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on osimertinib: surgery, radiotherapy, or radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events probably related to LAT.
|
Cohort 2: Definitely Related
Cohort 2 - Osimertinib followed by LAT followed by osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on osimertinib: surgery, radiotherapy, or radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events definitely related to LAT.
|
Cohort 3: Possibly Related
Cohort 3 - LAT followed by Osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events possibly related to LAT.
|
Cohort 3: Probably Related
Cohort 3 - LAT followed by Osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events probably related to LAT.
|
Cohort 3: Definitely Related
Cohort 3 - LAT followed by Osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events definitely related to LAT.
|
|---|---|---|---|---|---|---|---|---|---|
|
Progression Free Survival 1 (PFS 1) for ALL Participants Who Started Osimertinib on Trial Until First Progression of Disease or Clinical Progression, or Death Any Cause
|
14.7 Months
Interval 5.6 to 22.0
|
11.0 Months
Interval 5.5 to 25.7
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Retreatment Cycle 1 Day 1 (cycle is 28 days) to progression of disease, range 29-721 daysPFS2 = time from osimertinib re-challenge after LAT following first progression on osimertinib until second progression on osimertinib. Progression was evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and reported using the Kaplan Meier curve. Progressive Disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The appearance of one or more new lesions is also considered progression).
Outcome measures
| Measure |
All Participants in Cohort 1
n=21 Participants
COHORT 1: Osimertinib followed by LAT followed by osimertinib. Single daily dose of Osimertinib until progression. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation.
\*including germline T790M mutation
|
All Participants in Cohort 2
Cohort 2 - Osimertinib followed by LAT followed by osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on osimertinib: surgery, radiotherapy, or radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
|
Epidermal Growth Factor Receptor Mutated Non Small Cell Lung Cancer Progressed on Osimertinib
Cohort 3 - LAT followed by Osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
|
Cohort 2: Possibly Related
Cohort 2 - Osimertinib followed by LAT followed by osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on osimertinib: surgery, radiotherapy, or radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events possibly related to LAT.
|
Cohort 2: Probably Related
Cohort 2 - Osimertinib followed by LAT followed by osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on osimertinib: surgery, radiotherapy, or radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events probably related to LAT.
|
Cohort 2: Definitely Related
Cohort 2 - Osimertinib followed by LAT followed by osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on osimertinib: surgery, radiotherapy, or radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events definitely related to LAT.
|
Cohort 3: Possibly Related
Cohort 3 - LAT followed by Osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events possibly related to LAT.
|
Cohort 3: Probably Related
Cohort 3 - LAT followed by Osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events probably related to LAT.
|
Cohort 3: Definitely Related
Cohort 3 - LAT followed by Osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events definitely related to LAT.
|
|---|---|---|---|---|---|---|---|---|---|
|
Progression Free Survival 2 (PFS 2) - Local Ablative Therapy (LAT Eligible Only)
|
3.7 Months
Interval 1.9 to 4.6
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Retreatment Cycle 1 Day 1 (cycle is 28 days) to progression of disease, range 29-721 daysPopulation: This outcome measure reports data for LAT eligible participants only.
PFS2 = time from osimertinib re-challenge after LAT following first progression on osimertinib until second progression on osimertinib. Progression was evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and reported using the Kaplan Meier curve. Progressive Disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The appearance of one or more new lesions is also considered progression).
Outcome measures
| Measure |
All Participants in Cohort 1
n=12 Participants
COHORT 1: Osimertinib followed by LAT followed by osimertinib. Single daily dose of Osimertinib until progression. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation.
\*including germline T790M mutation
|
All Participants in Cohort 2
n=6 Participants
Cohort 2 - Osimertinib followed by LAT followed by osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on osimertinib: surgery, radiotherapy, or radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
|
Epidermal Growth Factor Receptor Mutated Non Small Cell Lung Cancer Progressed on Osimertinib
n=3 Participants
Cohort 3 - LAT followed by Osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
|
Cohort 2: Possibly Related
Cohort 2 - Osimertinib followed by LAT followed by osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on osimertinib: surgery, radiotherapy, or radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events possibly related to LAT.
|
Cohort 2: Probably Related
Cohort 2 - Osimertinib followed by LAT followed by osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on osimertinib: surgery, radiotherapy, or radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events probably related to LAT.
|
Cohort 2: Definitely Related
Cohort 2 - Osimertinib followed by LAT followed by osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on osimertinib: surgery, radiotherapy, or radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events definitely related to LAT.
|
Cohort 3: Possibly Related
Cohort 3 - LAT followed by Osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events possibly related to LAT.
|
Cohort 3: Probably Related
Cohort 3 - LAT followed by Osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events probably related to LAT.
|
Cohort 3: Definitely Related
Cohort 3 - LAT followed by Osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events definitely related to LAT.
|
|---|---|---|---|---|---|---|---|---|---|
|
Progression Free Survival 2 (PFS 2) - Local Ablative Therapy (LAT Eligible Only) - Cohort 1, Cohort 2, and Cohort 3
|
4.0 Months
Interval 1.0 to 16.5
|
3.6 Months
Interval 1.8 to 4.6
|
3.7 Months
Interval 2.3 to 23.9
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.Adverse events were assessed by the by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
Outcome measures
| Measure |
All Participants in Cohort 1
n=25 Participants
COHORT 1: Osimertinib followed by LAT followed by osimertinib. Single daily dose of Osimertinib until progression. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation.
\*including germline T790M mutation
|
All Participants in Cohort 2
n=9 Participants
Cohort 2 - Osimertinib followed by LAT followed by osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on osimertinib: surgery, radiotherapy, or radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
|
Epidermal Growth Factor Receptor Mutated Non Small Cell Lung Cancer Progressed on Osimertinib
n=3 Participants
Cohort 3 - LAT followed by Osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
|
Cohort 2: Possibly Related
Cohort 2 - Osimertinib followed by LAT followed by osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on osimertinib: surgery, radiotherapy, or radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events possibly related to LAT.
|
Cohort 2: Probably Related
Cohort 2 - Osimertinib followed by LAT followed by osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on osimertinib: surgery, radiotherapy, or radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events probably related to LAT.
|
Cohort 2: Definitely Related
Cohort 2 - Osimertinib followed by LAT followed by osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on osimertinib: surgery, radiotherapy, or radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events definitely related to LAT.
|
Cohort 3: Possibly Related
Cohort 3 - LAT followed by Osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events possibly related to LAT.
|
Cohort 3: Probably Related
Cohort 3 - LAT followed by Osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events probably related to LAT.
|
Cohort 3: Definitely Related
Cohort 3 - LAT followed by Osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events definitely related to LAT.
|
|---|---|---|---|---|---|---|---|---|---|
|
Serious Adverse Events Possibly, Probably, and/or Definitely Related to Treatment
Anemia - Possibly Related
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Serious Adverse Events Possibly, Probably, and/or Definitely Related to Treatment
Lung Infection - Possibly Related
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Serious Adverse Events Possibly, Probably, and/or Definitely Related to Treatment
Peripheral Sensory Neuropathy Possibly Related
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Serious Adverse Events Possibly, Probably, and/or Definitely Related to Treatment
Pleural Effusion - Possibly Related
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Serious Adverse Events Possibly, Probably, and/or Definitely Related to Treatment
Thromboembolic Event - Definitely Related
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). Grade 1 is mild. Grade 2 is moderate. Grade 3 is severe. Grade 4 is life-threatening. Grade 5 is death related to adverse events.
Outcome measures
| Measure |
All Participants in Cohort 1
n=25 Participants
COHORT 1: Osimertinib followed by LAT followed by osimertinib. Single daily dose of Osimertinib until progression. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation.
\*including germline T790M mutation
|
All Participants in Cohort 2
n=25 Participants
Cohort 2 - Osimertinib followed by LAT followed by osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on osimertinib: surgery, radiotherapy, or radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
|
Epidermal Growth Factor Receptor Mutated Non Small Cell Lung Cancer Progressed on Osimertinib
n=25 Participants
Cohort 3 - LAT followed by Osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
|
Cohort 2: Possibly Related
n=9 Participants
Cohort 2 - Osimertinib followed by LAT followed by osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on osimertinib: surgery, radiotherapy, or radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events possibly related to LAT.
|
Cohort 2: Probably Related
n=9 Participants
Cohort 2 - Osimertinib followed by LAT followed by osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on osimertinib: surgery, radiotherapy, or radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events probably related to LAT.
|
Cohort 2: Definitely Related
n=9 Participants
Cohort 2 - Osimertinib followed by LAT followed by osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on osimertinib: surgery, radiotherapy, or radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events definitely related to LAT.
|
Cohort 3: Possibly Related
n=3 Participants
Cohort 3 - LAT followed by Osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events possibly related to LAT.
|
Cohort 3: Probably Related
n=3 Participants
Cohort 3 - LAT followed by Osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events probably related to LAT.
|
Cohort 3: Definitely Related
n=3 Participants
Cohort 3 - LAT followed by Osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events definitely related to LAT.
|
|---|---|---|---|---|---|---|---|---|---|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Abdominal pain - Grade 3
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Alanine aminotransferase increased - Grade 1
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Alanine aminotransferase - increased - Grade 2
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Alanine aminotransferase - increased - Grade 3
|
1 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Alkaline phosphatase increased - Grade 1
|
1 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Anemia -Grade 1
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Anemia - Grade 2
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Anorexia - Grade 1
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
2 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Arthralgia - Grade 2
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Aspartate aminotransferase increased - Grade 1
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Aspartate aminotransferase increased - Grade 2
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Aspartate aminotransferase increased - Grade 3
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Atelectasis - Grade 1
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Bloating - Grade 2
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Blurred vision - Grade 1
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
CPK increased - Grade 2
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Cough - Grade 1
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Cough - Grade 2
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Dizziness - Grade 1
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
2 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Dry mouth - Grade 1
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Dysgeusia - Grade 1
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Dyspnea - Grade 1
|
1 adverse events
|
1 adverse events
|
0 adverse events
|
2 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Dyspnea - Grade 2
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Electrocardiogram QT corrected interval prolonged - Grade 2
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Eyelid function disorder - Grade 1
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Fall - Grade 1
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Fever - Grade 1
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Hypokalemia - Grade 1
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Hypophosphatemia - Grade 2
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Hypophosphatemia - Grade 3
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Hypotension - Grade 1
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Hypotension - Grade 2
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Hypoxia - Grade 3
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Localized edema - Grade 1
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Lymphocyte count decreased - Grade 2
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Lymphocyte count decreased - Grade 3
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Muscle weakness upper limb - Grade 1
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Muscle weakness lower limb - Grade 2
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Muscle weakness lower limb - Grade 3
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Nausea - Grade 1
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Non-cardiac chest pain - Grade 1
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Non-cardiac chest pain - Grade 2
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Pain - Grade 1
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Pain - Grade 2
|
3 adverse events
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Pain - Grade 3
|
1 adverse events
|
0 adverse events
|
1 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Pain in extremity - Grade 2
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Paresthesia - Grade 1
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Pericardial effusion - Grade 2
|
2 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Peripheral sensory neuropathy - Grade 1
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Pleural effusion - Grade 1
|
2 adverse events
|
2 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Pleural effusion - Grade 2
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
2 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Pleural effusion - Grade 3
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Pneumothorax - Grade 1
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Pneumothorax - Grade 2
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Respiratory, thoracic and mediastinal disorders - Other, Hydropneumothorax - Grade 1
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Respiratory, thoracic and mediastinal disorders - Hydropneumothorax - Grade 2
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Respiratory, thoracic and mediastinal disorders - Other, Subcutaneous emphysema - Grade 1
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Sore throat - Grade 1
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Sinus tachycardia - Grade 2
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Surgical and medical procedures - Other, incision site pain - Grade 1
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Surgical and medical procedures - Other, incision site pain - Grade 2
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Tinnitus - Grade 1
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Urinary retention - Grade 2
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Vomiting - Grade 2
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Wheezing - Grade 1
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
2 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Local Ablative Therapy (LAT)
Wheezing - Grade 2
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
PRIMARY outcome
Timeframe: Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.Population: \*Because this adverse event has attribution to local ablative therapy (LAT) as well.
Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). Grade 1 is mild. Grade 2 is moderate. Grade 3 is severe. Grade 4 is life-threatening. Grade 5 is death related to adverse events.
Outcome measures
| Measure |
All Participants in Cohort 1
n=25 Participants
COHORT 1: Osimertinib followed by LAT followed by osimertinib. Single daily dose of Osimertinib until progression. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation.
\*including germline T790M mutation
|
All Participants in Cohort 2
n=25 Participants
Cohort 2 - Osimertinib followed by LAT followed by osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on osimertinib: surgery, radiotherapy, or radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
|
Epidermal Growth Factor Receptor Mutated Non Small Cell Lung Cancer Progressed on Osimertinib
n=25 Participants
Cohort 3 - LAT followed by Osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
|
Cohort 2: Possibly Related
n=9 Participants
Cohort 2 - Osimertinib followed by LAT followed by osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on osimertinib: surgery, radiotherapy, or radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events possibly related to LAT.
|
Cohort 2: Probably Related
n=9 Participants
Cohort 2 - Osimertinib followed by LAT followed by osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on osimertinib: surgery, radiotherapy, or radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events probably related to LAT.
|
Cohort 2: Definitely Related
n=9 Participants
Cohort 2 - Osimertinib followed by LAT followed by osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on osimertinib: surgery, radiotherapy, or radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events definitely related to LAT.
|
Cohort 3: Possibly Related
n=3 Participants
Cohort 3 - LAT followed by Osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events possibly related to LAT.
|
Cohort 3: Probably Related
n=3 Participants
Cohort 3 - LAT followed by Osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events probably related to LAT.
|
Cohort 3: Definitely Related
n=3 Participants
Cohort 3 - LAT followed by Osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events definitely related to LAT.
|
|---|---|---|---|---|---|---|---|---|---|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Dyspepsia - Grade 1
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Dyspepsia - Grade 2
|
3 adverse events
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Dyspnea - Grade 1
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Edema limbs - Grade 1
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Electrocardiogram QT corrected interval prolonged - Grade 2
|
2 adverse events
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Esophagitis - Grade 2
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Fatigue - Grade 1
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
4 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Fatigue - Grade 2
|
2 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Floaters - Grade 1
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Bloating - Grade 1
|
2 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Blurred vision - Grade 1
|
3 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Gastritis - Grade 2
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Gastroesophageal reflux disease - Grade 1
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Gastroesophageal reflux disease - Grade 2
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Gastrointestinal disorders - Other, stomatitis - Grade 2
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Edema face - Grade 1
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Headache - Grade 1
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Headache - Grade 2
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Hypertension - Grade 1
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Hypoglycemia - Grade 1
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Hypophosphatemia - Grade 2
|
3 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Lung infection - Grade 3
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Lymphocyte count decreased - Grade 1
|
4 adverse events
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Blurred vision - Grade 1*
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Lymphocyte count decreased - Grade 2
|
3 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
2 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Lymphocyte count decreased - Grade 2*
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Diarrhea - Grade 1
|
4 adverse events
|
6 adverse events
|
4 adverse events
|
4 adverse events
|
2 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Lymphocyte count decreased - Grade 4
|
2 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Metabolism and nutrition disorders - Other, muscle cramps - Grade 1
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Mucositis oral - Grade 1
|
2 adverse events
|
4 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Nail infection - Grade 2
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Nail loss - Grade 2
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Nausea - Grade 1
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Nausea - Grade 2
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Neutrophil count decreased - Grade 2
|
4 adverse events
|
3 adverse events
|
0 adverse events
|
3 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Neutrophil count decreased - Grade 3
|
14 adverse events
|
4 adverse events
|
0 adverse events
|
0 adverse events
|
2 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Neutrophil count decreased - Grade 4
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Rash pustular - Grade 2
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
White blood cell decreased - Grade 3
|
16 adverse events
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Diarrhea - Grade 2
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Dry eye - Grade 1
|
3 adverse events
|
4 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
1 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Dry mouth - Grade 1
|
2 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Rash maculo-papular - Grade 1
|
12 adverse events
|
7 adverse events
|
3 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Nail loss - Grade 1
|
1 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Dizziness - Grade 1
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Alanine aminotransferase increased - Grade 1
|
1 adverse events
|
1 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Alanine aminotransferase increased - Grade 3
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Alkaline phosphatase increased - Grade 1
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Alopecia - Grade 1
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Anemia - Grade 1
|
0 adverse events
|
2 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Anemia - Grade 1*
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Anemia - Grade 2
|
7 adverse events
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Anemia - Grade 3
|
3 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Anorexia - Grade 1
|
3 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Arthralgia - Grade 1
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Aspartate aminotransferase increased - Grade 1
|
1 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Aspartate aminotransferase increased - Grade 3
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Dry skin - Grade 1
|
9 adverse events
|
3 adverse events
|
1 adverse events
|
3 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Dry skin - Grade 2
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
1 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Hyperglycemia - Grade 2
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Buttock pain - Grade 1
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
CPK increased - Grade 1
|
11 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
CPK increased - Grade 2
|
5 adverse events
|
4 adverse events
|
0 adverse events
|
7 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
CPK increased - Grade 3
|
1 adverse events
|
1 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Dysgeusia - Grade 1
|
1 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
CPK increased - Grade 4
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Constipation - Grade 1
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Cough - Grade 1
|
3 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Lymphocyte count decreased - Grade 3*
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Hypokalemia - Grade 2
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Dyspnea - Grade 2
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Electrocardiogram QT corrected interval prolonged - Grade 1
|
9 adverse events
|
2 adverse events
|
0 adverse events
|
12 adverse events
|
5 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Electrocardiogram QT corrected interval prolonged - Grade 2*
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
2 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Eye pain - Grade 1
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Gastrointestinal disorders - Other, stomatitis - Grade 1
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Palmar-plantar erythrodysesthesia syndrome - Grade 1
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Mucositis oral - Grade 2
|
1 adverse events
|
3 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Mucositis oral - Grade 3
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Myalgia - Grade 1
|
1 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Myalgia - Grade 2
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Lymphocyte count decreased - Grade 3
|
19 adverse events
|
1 adverse events
|
0 adverse events
|
4 adverse events
|
1 adverse events
|
0 adverse events
|
2 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Palmar-plantar erythrodysesthesia syndrome - Grade 2
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Papulopustular rash - Grade 1
|
2 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Papulopustular rash - Grade 2
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Paronychia - Grade 1
|
1 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Paronychia - Grade 2
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
1 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Nail ridging - Grade 1
|
4 adverse events
|
2 adverse events
|
1 adverse events
|
1 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Peripheral sensory neuropathy - Grade 1
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Photophobia - Grade 1
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Non-cardiac chest pain - Grade 1
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Platelet count decreased - Grade 1
|
3 adverse events
|
4 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
2 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Platelet count decreased - Grade 2
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Platelet count decreased - Grade 3
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Pleural effusion - Grade 1
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Productive cough -Grade 2
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Pruritis - Grade 1
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Pruritis - Grade 2
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Rash acneiform - Grade 1
|
0 adverse events
|
3 adverse events
|
3 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Rash acneiform - Grade 2
|
0 adverse events
|
1 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Rash maculo-papular - Grade 2
|
0 adverse events
|
3 adverse events
|
1 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Rash maculo-papular - Grade 3
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Skin and subcutaneous tissue disorders - Other, Cracks around fingertips - Grade 1
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Skin and subcutaneous tissue disorders - Crack right and left thumb and left 3rd finger - Grade 2
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Skin hypopigmentation - Grade 1
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Skin and subcutaneous tissue disorders - Other, mild cracks at fingertips - Grade 1
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Thromboembolic event - Grade 4
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Vomiting - Grade 1
|
4 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Watering eyes - Grade 1
|
2 adverse events
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Watering eyes - Grade 2
|
2 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Weight loss - Grade 1
|
2 adverse events
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Weight loss - Grade 2
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
White blood cell decreased - Grade 1
|
2 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
1 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
White blood cell decreased - Grade 2
|
5 adverse events
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
|
All Grades 1, Grade 2, Grade 3, Grade 4, and/or Grade 5 Adverse Events Possibly, Probably, and/or Definitely Related to Osimertinib
Pain in extremity - Grade 1
|
1 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
0 adverse events
|
PRIMARY outcome
Timeframe: up to 757 daysPopulation: 15/37 participants had tissue available for analysis and 2/37 participants were censored.
Whole-exome sequencing (WES), targeted sequencing and ribonucleic acid (RNA)-seq was performed on tumors to identify Osimertinib acquired resistant mechanisms. Sequencing can help identify mutations/heterogeneity that may impact a participant prognosis.
Outcome measures
| Measure |
All Participants in Cohort 1
n=9 Participants
COHORT 1: Osimertinib followed by LAT followed by osimertinib. Single daily dose of Osimertinib until progression. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation.
\*including germline T790M mutation
|
All Participants in Cohort 2
n=3 Participants
Cohort 2 - Osimertinib followed by LAT followed by osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on osimertinib: surgery, radiotherapy, or radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
|
Epidermal Growth Factor Receptor Mutated Non Small Cell Lung Cancer Progressed on Osimertinib
n=3 Participants
Cohort 3 - LAT followed by Osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
|
Cohort 2: Possibly Related
Cohort 2 - Osimertinib followed by LAT followed by osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on osimertinib: surgery, radiotherapy, or radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events possibly related to LAT.
|
Cohort 2: Probably Related
Cohort 2 - Osimertinib followed by LAT followed by osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on osimertinib: surgery, radiotherapy, or radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events probably related to LAT.
|
Cohort 2: Definitely Related
Cohort 2 - Osimertinib followed by LAT followed by osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on osimertinib: surgery, radiotherapy, or radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events definitely related to LAT.
|
Cohort 3: Possibly Related
Cohort 3 - LAT followed by Osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events possibly related to LAT.
|
Cohort 3: Probably Related
Cohort 3 - LAT followed by Osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events probably related to LAT.
|
Cohort 3: Definitely Related
Cohort 3 - LAT followed by Osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events definitely related to LAT.
|
|---|---|---|---|---|---|---|---|---|---|
|
Number of Participants Who Had Osimertinib Acquired Resistant Mechanisms Identified on Tumors
≥1 resistance mechanisms
|
9 Participants
|
3 Participants
|
3 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants Who Had Osimertinib Acquired Resistant Mechanisms Identified on Tumors
2 or more resistance mechanisms co-occurring
|
8 Participants
|
2 Participants
|
2 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: up to 757 daysPopulation: 15/37 participants had tissue available for analysis and 2/37 participants were censored.
Whole-exome sequencing (WES), targeted sequencing and ribonucleic acid (RNA)-seq was performed on tumors for first and second line Osimertinib treatment to identify Osimertinib acquired resistant mechanisms. Sequencing can help identify mutations (i.e., NE-differentiation, ribonucleic acid (RNA), v-raf murine sarcoma viral oncogene homolog B1 (BRAF), other amps, etc.)/heterogeneity that may impact a participant prognosis.
Outcome measures
| Measure |
All Participants in Cohort 1
n=9 Participants
COHORT 1: Osimertinib followed by LAT followed by osimertinib. Single daily dose of Osimertinib until progression. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation.
\*including germline T790M mutation
|
All Participants in Cohort 2
n=3 Participants
Cohort 2 - Osimertinib followed by LAT followed by osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on osimertinib: surgery, radiotherapy, or radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
|
Epidermal Growth Factor Receptor Mutated Non Small Cell Lung Cancer Progressed on Osimertinib
n=3 Participants
Cohort 3 - LAT followed by Osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
|
Cohort 2: Possibly Related
Cohort 2 - Osimertinib followed by LAT followed by osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on osimertinib: surgery, radiotherapy, or radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events possibly related to LAT.
|
Cohort 2: Probably Related
Cohort 2 - Osimertinib followed by LAT followed by osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on osimertinib: surgery, radiotherapy, or radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events probably related to LAT.
|
Cohort 2: Definitely Related
Cohort 2 - Osimertinib followed by LAT followed by osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on osimertinib: surgery, radiotherapy, or radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events definitely related to LAT.
|
Cohort 3: Possibly Related
Cohort 3 - LAT followed by Osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events possibly related to LAT.
|
Cohort 3: Probably Related
Cohort 3 - LAT followed by Osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events probably related to LAT.
|
Cohort 3: Definitely Related
Cohort 3 - LAT followed by Osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events definitely related to LAT.
|
|---|---|---|---|---|---|---|---|---|---|
|
Number of Participants Who Had Osimertinib Acquired Resistant Mechanisms Identified on Tumors With First Line and/or Second Line Treatment
Casitas B-lineage lymphoma(Cbl), Kirsten Rat Sarcoma(KRAS),MET&other amplification (amps)-First Line
|
1 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants Who Had Osimertinib Acquired Resistant Mechanisms Identified on Tumors With First Line and/or Second Line Treatment
mesenchymal epithelial transition factor receptor (MET) amps -First Line
|
1 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants Who Had Osimertinib Acquired Resistant Mechanisms Identified on Tumors With First Line and/or Second Line Treatment
Epidermal growth factor receptor (EGFR) amp & EGFR C797S mutation - Second Line
|
0 Participants
|
1 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants Who Had Osimertinib Acquired Resistant Mechanisms Identified on Tumors With First Line and/or Second Line Treatment
Small Cell Lung Cancer (SCLC) transformation - Second Line
|
0 Participants
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants Who Had Osimertinib Acquired Resistant Mechanisms Identified on Tumors With First Line and/or Second Line Treatment
Epidermal growth factor receptor (EGFR), MET amp & tumor protein P53 (TP53) A24fs -First Line
|
1 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants Who Had Osimertinib Acquired Resistant Mechanisms Identified on Tumors With First Line and/or Second Line Treatment
TP53 G112V & Catenin Beta 1(CTNNB1) Substitution-Missense,position 33, S➞C(S33C)mutations-First Line
|
0 Participants
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants Who Had Osimertinib Acquired Resistant Mechanisms Identified on Tumors With First Line and/or Second Line Treatment
Mixed Non-Small Cell Lung Cancer (NSCLC) & Small Cell Lung Cancer (SCLC) transformation - First Line
|
1 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants Who Had Osimertinib Acquired Resistant Mechanisms Identified on Tumors With First Line and/or Second Line Treatment
Unknown by exome; NE-differentiation without histologic transformation by RNA-seq-Second Line
|
0 Participants
|
1 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants Who Had Osimertinib Acquired Resistant Mechanisms Identified on Tumors With First Line and/or Second Line Treatment
Epidermal growth factor receptor (EGFR), Kirsten Rat Sarcoma (KRAS) & MET amp - First Line
|
1 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants Who Had Osimertinib Acquired Resistant Mechanisms Identified on Tumors With First Line and/or Second Line Treatment
mesenchymal epithelial transition factor receptor (MET) & other amps & EGFR C797S- Second Line
|
1 Participants
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants Who Had Osimertinib Acquired Resistant Mechanisms Identified on Tumors With First Line and/or Second Line Treatment
AGK(2) - BRAF(8) fusion & Makorin Ring Finger Protein 1 (MKRN1)(4) - BRAF(11) fusion - Second Line
|
0 Participants
|
1 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants Who Had Osimertinib Acquired Resistant Mechanisms Identified on Tumors With First Line and/or Second Line Treatment
Epidermal growth factor receptor (EGFR) & YES1 amp - Second Line
|
1 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants Who Had Osimertinib Acquired Resistant Mechanisms Identified on Tumors With First Line and/or Second Line Treatment
CD274 Programmed death-ligand 1 (PD-L1) & MET amp - First Line
|
1 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants Who Had Osimertinib Acquired Resistant Mechanisms Identified on Tumors With First Line and/or Second Line Treatment
Epidermal growth factor receptor(EGFR) C797S&estrogen receptor 1(ESR1(6)-AKAP12(4) fusion-First Line
|
1 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants Who Had Osimertinib Acquired Resistant Mechanisms Identified on Tumors With First Line and/or Second Line Treatment
Epidermal growth factor receptor(EGFR) & MET amp - First Line
|
1 Participants
|
0 Participants
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: end of treatment, up to 693 daysPopulation: One participant was not evaluable for response in Cohort 1. Cohort 3 did not have a first treatment of Osimertinib on this protocol.
Best Overall Response is defined as a Complete Response (CR) + Partial Response (PR) and is recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The participant's best response assignment will depend on the achievement of both measurement and confirmation criteria. Response was evaluated in this study using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Complete Response (CR) is disappearance of all target lesions, determined by two separate observations conducted not less than 4 weeks apart. Any pathological lymph nodes must have reduction in short axis to \<10 mm. Partial Response (PR) is at least a 30% decrease in the sum of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD) is at least a 20% increase in the sum of the diameters of target lesions.
Outcome measures
| Measure |
All Participants in Cohort 1
n=25 Participants
COHORT 1: Osimertinib followed by LAT followed by osimertinib. Single daily dose of Osimertinib until progression. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation.
\*including germline T790M mutation
|
All Participants in Cohort 2
n=9 Participants
Cohort 2 - Osimertinib followed by LAT followed by osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on osimertinib: surgery, radiotherapy, or radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
|
Epidermal Growth Factor Receptor Mutated Non Small Cell Lung Cancer Progressed on Osimertinib
n=3 Participants
Cohort 3 - LAT followed by Osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
|
Cohort 2: Possibly Related
Cohort 2 - Osimertinib followed by LAT followed by osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on osimertinib: surgery, radiotherapy, or radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events possibly related to LAT.
|
Cohort 2: Probably Related
Cohort 2 - Osimertinib followed by LAT followed by osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on osimertinib: surgery, radiotherapy, or radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events probably related to LAT.
|
Cohort 2: Definitely Related
Cohort 2 - Osimertinib followed by LAT followed by osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on osimertinib: surgery, radiotherapy, or radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events definitely related to LAT.
|
Cohort 3: Possibly Related
Cohort 3 - LAT followed by Osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events possibly related to LAT.
|
Cohort 3: Probably Related
Cohort 3 - LAT followed by Osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events probably related to LAT.
|
Cohort 3: Definitely Related
Cohort 3 - LAT followed by Osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events definitely related to LAT.
|
|---|---|---|---|---|---|---|---|---|---|
|
Best Overall Response (BOR)
First Treatment - Complete Response + Partial Response
|
70.8 percentage of participants
|
66.7 percentage of participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Best Overall Response (BOR)
Second Treatment - Complete Response + Partial Response
|
0.0 percentage of participants
|
0.0 percentage of participants
|
0.0 percentage of participants
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: end of treatment, up to 693 daysPopulation: One participant was not evaluable for response in Cohort 1. Cohort 3 did not have a first treatment of Osimertinib on this protocol.
Best Overall Response is defined as a Complete Response (CR) + Partial Response (PR) and is recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The participant's best response assignment will depend on the achievement of both measurement and confirmation criteria. Response was evaluated in this study using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Complete Response (CR) is disappearance of all target lesions, determined by two separate observations conducted not less than 4 weeks apart. Any pathological lymph nodes must have reduction in short axis to \<10 mm. Partial Response (PR) is at least a 30% decrease in the sum of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD) is at least a 20% increase in the sum of the diameters of target lesions.
Outcome measures
| Measure |
All Participants in Cohort 1
n=36 Participants
COHORT 1: Osimertinib followed by LAT followed by osimertinib. Single daily dose of Osimertinib until progression. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation.
\*including germline T790M mutation
|
All Participants in Cohort 2
Cohort 2 - Osimertinib followed by LAT followed by osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on osimertinib: surgery, radiotherapy, or radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
|
Epidermal Growth Factor Receptor Mutated Non Small Cell Lung Cancer Progressed on Osimertinib
Cohort 3 - LAT followed by Osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
|
Cohort 2: Possibly Related
Cohort 2 - Osimertinib followed by LAT followed by osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on osimertinib: surgery, radiotherapy, or radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events possibly related to LAT.
|
Cohort 2: Probably Related
Cohort 2 - Osimertinib followed by LAT followed by osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on osimertinib: surgery, radiotherapy, or radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events probably related to LAT.
|
Cohort 2: Definitely Related
Cohort 2 - Osimertinib followed by LAT followed by osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on osimertinib: surgery, radiotherapy, or radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events definitely related to LAT.
|
Cohort 3: Possibly Related
Cohort 3 - LAT followed by Osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events possibly related to LAT.
|
Cohort 3: Probably Related
Cohort 3 - LAT followed by Osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events probably related to LAT.
|
Cohort 3: Definitely Related
Cohort 3 - LAT followed by Osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events definitely related to LAT.
|
|---|---|---|---|---|---|---|---|---|---|
|
Best Overall Response - All Participants
First treatment - Complete Response + Partial Response
|
69.7 percentage of participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Best Overall Response - All Participants
Second treatment - Complete Response + Partial Response
|
0.0 percentage of participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Duration of time from start of treatment to death from any cause. An average of 35.95 months.Population: Analysis was performed for participants who underwent LAT in Cohorts 1 (n=13/24) and 2 (n=5/9) with initial Osimertinib start date as the start date of OS. Cohort 3 is not applicable for this outcome measure because these participants enrolled in the study after getting Osimertinib at an outside institution. One participant in Cohort 1 was not evaluable.
Overall survival is defined as the duration of time from start of treatment to death from any cause.
Outcome measures
| Measure |
All Participants in Cohort 1
n=13 Participants
COHORT 1: Osimertinib followed by LAT followed by osimertinib. Single daily dose of Osimertinib until progression. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation.
\*including germline T790M mutation
|
All Participants in Cohort 2
n=5 Participants
Cohort 2 - Osimertinib followed by LAT followed by osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on osimertinib: surgery, radiotherapy, or radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
|
Epidermal Growth Factor Receptor Mutated Non Small Cell Lung Cancer Progressed on Osimertinib
Cohort 3 - LAT followed by Osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
|
Cohort 2: Possibly Related
Cohort 2 - Osimertinib followed by LAT followed by osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on osimertinib: surgery, radiotherapy, or radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events possibly related to LAT.
|
Cohort 2: Probably Related
Cohort 2 - Osimertinib followed by LAT followed by osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on osimertinib: surgery, radiotherapy, or radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events probably related to LAT.
|
Cohort 2: Definitely Related
Cohort 2 - Osimertinib followed by LAT followed by osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on osimertinib: surgery, radiotherapy, or radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events definitely related to LAT.
|
Cohort 3: Possibly Related
Cohort 3 - LAT followed by Osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events possibly related to LAT.
|
Cohort 3: Probably Related
Cohort 3 - LAT followed by Osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events probably related to LAT.
|
Cohort 3: Definitely Related
Cohort 3 - LAT followed by Osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events definitely related to LAT.
|
|---|---|---|---|---|---|---|---|---|---|
|
Overall Survival
|
38.2 Months
Interval 16.3 to 56.3
|
33.7 Months
Interval 18.5 to 40.3
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: end of treatment, up to 693 daysPopulation: One participant was not evaluable for response in Cohort 1. Cohort 3 did not have a first treatment of Osimertinib on this protocol.
DCR is defined as a Complete Response (CR) + Partial Response (PR) + Stable Disease (SD). Response was evaluated in this study using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Complete Response (CR) is disappearance of all target lesions, determined by two separate observations conducted not less than 4 weeks apart. Any pathological lymph nodes must have reduction in short axis to \<10 mm. Partial Response (PR) is at least a 30% decrease in the sum of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease (PD), taking as reference the smallest sum diameters while on study. PD is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. The appearance of one or more new lesions is also considered progression.
Outcome measures
| Measure |
All Participants in Cohort 1
n=25 Participants
COHORT 1: Osimertinib followed by LAT followed by osimertinib. Single daily dose of Osimertinib until progression. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation.
\*including germline T790M mutation
|
All Participants in Cohort 2
n=9 Participants
Cohort 2 - Osimertinib followed by LAT followed by osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on osimertinib: surgery, radiotherapy, or radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
|
Epidermal Growth Factor Receptor Mutated Non Small Cell Lung Cancer Progressed on Osimertinib
n=3 Participants
Cohort 3 - LAT followed by Osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
|
Cohort 2: Possibly Related
Cohort 2 - Osimertinib followed by LAT followed by osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on osimertinib: surgery, radiotherapy, or radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events possibly related to LAT.
|
Cohort 2: Probably Related
Cohort 2 - Osimertinib followed by LAT followed by osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on osimertinib: surgery, radiotherapy, or radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events probably related to LAT.
|
Cohort 2: Definitely Related
Cohort 2 - Osimertinib followed by LAT followed by osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on osimertinib: surgery, radiotherapy, or radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events definitely related to LAT.
|
Cohort 3: Possibly Related
Cohort 3 - LAT followed by Osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events possibly related to LAT.
|
Cohort 3: Probably Related
Cohort 3 - LAT followed by Osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events probably related to LAT.
|
Cohort 3: Definitely Related
Cohort 3 - LAT followed by Osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events definitely related to LAT.
|
|---|---|---|---|---|---|---|---|---|---|
|
Disease Control Rate (DCR)
First Treatment - Complete Response + Partial Response + Stable Disease
|
100 percentage of participants
|
100 percentage of participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Disease Control Rate (DCR)
Second Treatment - Complete Response + Partial Response + Stable Disease
|
66.7 percentage of participants
|
50.0 percentage of participants
|
100 percentage of participants
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: end of treatment, up to 693 daysPopulation: One participant was not evaluable for response in Cohort 1. Cohort 3 did not have a first treatment of Osimertinib on this protocol.
DCR is defined as a Complete Response (CR) + Partial Response (PR) + Stable Disease (SD). Response was evaluated in this study using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Complete Response (CR) is disappearance of all target lesions, determined by two separate observations conducted not less than 4 weeks apart. Any pathological lymph nodes must have reduction in short axis to \<10 mm. Partial Response (PR) is at least a 30% decrease in the sum of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease (PD), taking as reference the smallest sum diameters while on study. PD is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. The appearance of one or more new lesions is also considered progression.
Outcome measures
| Measure |
All Participants in Cohort 1
n=36 Participants
COHORT 1: Osimertinib followed by LAT followed by osimertinib. Single daily dose of Osimertinib until progression. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation.
\*including germline T790M mutation
|
All Participants in Cohort 2
Cohort 2 - Osimertinib followed by LAT followed by osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on osimertinib: surgery, radiotherapy, or radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
|
Epidermal Growth Factor Receptor Mutated Non Small Cell Lung Cancer Progressed on Osimertinib
Cohort 3 - LAT followed by Osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
|
Cohort 2: Possibly Related
Cohort 2 - Osimertinib followed by LAT followed by osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on osimertinib: surgery, radiotherapy, or radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events possibly related to LAT.
|
Cohort 2: Probably Related
Cohort 2 - Osimertinib followed by LAT followed by osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on osimertinib: surgery, radiotherapy, or radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events probably related to LAT.
|
Cohort 2: Definitely Related
Cohort 2 - Osimertinib followed by LAT followed by osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on osimertinib: surgery, radiotherapy, or radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events definitely related to LAT.
|
Cohort 3: Possibly Related
Cohort 3 - LAT followed by Osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events possibly related to LAT.
|
Cohort 3: Probably Related
Cohort 3 - LAT followed by Osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events probably related to LAT.
|
Cohort 3: Definitely Related
Cohort 3 - LAT followed by Osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events definitely related to LAT.
|
|---|---|---|---|---|---|---|---|---|---|
|
Disease Control Rate (DCR) - All Participants
First Treatment - Complete Response + Partial Response + Stable Disease
|
100 percentage of participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Disease Control Rate (DCR) - All Participants
Second Treatment - Complete Response + Partial Response + Stable Disease
|
66.7 percentage of participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
Outcome measures
| Measure |
All Participants in Cohort 1
n=25 Participants
COHORT 1: Osimertinib followed by LAT followed by osimertinib. Single daily dose of Osimertinib until progression. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation.
\*including germline T790M mutation
|
All Participants in Cohort 2
n=9 Participants
Cohort 2 - Osimertinib followed by LAT followed by osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on osimertinib: surgery, radiotherapy, or radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
|
Epidermal Growth Factor Receptor Mutated Non Small Cell Lung Cancer Progressed on Osimertinib
n=3 Participants
Cohort 3 - LAT followed by Osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
|
Cohort 2: Possibly Related
Cohort 2 - Osimertinib followed by LAT followed by osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on osimertinib: surgery, radiotherapy, or radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events possibly related to LAT.
|
Cohort 2: Probably Related
Cohort 2 - Osimertinib followed by LAT followed by osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on osimertinib: surgery, radiotherapy, or radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events probably related to LAT.
|
Cohort 2: Definitely Related
Cohort 2 - Osimertinib followed by LAT followed by osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on osimertinib: surgery, radiotherapy, or radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events definitely related to LAT.
|
Cohort 3: Possibly Related
Cohort 3 - LAT followed by Osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events possibly related to LAT.
|
Cohort 3: Probably Related
Cohort 3 - LAT followed by Osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events probably related to LAT.
|
Cohort 3: Definitely Related
Cohort 3 - LAT followed by Osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
Adverse events definitely related to LAT.
|
|---|---|---|---|---|---|---|---|---|---|
|
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)
|
25 Participants
|
9 Participants
|
3 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
Adverse Events
Tyrosine Kinase Inhibitor Naïve Epidermal Growth Factor Receptor *Mutated Non Small Cell Lung Cancer
Serious events: 14 serious events
Other events: 24 other events
Deaths: 15 deaths
EGFR Mutated NSCLC Progressed on Prior 1st/2nd Generation EGFR TKI Therapy &Acquired T790M Mutation
Serious events: 5 serious events
Other events: 9 other events
Deaths: 7 deaths
Epidermal Growth Factor Receptor Mutated Non Small Cell Lung Cancer Progressed on Osimertinib
Serious events: 2 serious events
Other events: 3 other events
Deaths: 3 deaths
Serious adverse events
| Measure |
Tyrosine Kinase Inhibitor Naïve Epidermal Growth Factor Receptor *Mutated Non Small Cell Lung Cancer
n=25 participants at risk
COHORT 1: Osimertinib followed by LAT followed by osimertinib. Single daily dose of Osimertinib until progression. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation.
\*including germline T790M mutation
|
EGFR Mutated NSCLC Progressed on Prior 1st/2nd Generation EGFR TKI Therapy &Acquired T790M Mutation
n=9 participants at risk
Cohort 2 - Osimertinib followed by LAT followed by osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on osimertinib: surgery, radiotherapy, or radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
|
Epidermal Growth Factor Receptor Mutated Non Small Cell Lung Cancer Progressed on Osimertinib
n=3 participants at risk
Cohort 3 - LAT followed by Osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
|
|---|---|---|---|
|
Metabolism and nutrition disorders
Hypercalcemia
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Blood and lymphatic system disorders
Anemia
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
33.3%
1/3 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Respiratory, thoracic and mediastinal disorders
Bronchial obstruction
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
General disorders
Death NOS
|
0.00%
0/25 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Metabolism and nutrition disorders
Dehydration
|
4.0%
1/25 • Number of events 3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Nervous system disorders
Dizziness
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
8.0%
2/25 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
General disorders
Edema limbs
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
General disorders
Fatigue
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Ear and labyrinth disorders
Hearing impaired
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Vascular disorders
Hypotension
|
0.00%
0/25 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Gastrointestinal disorders
Ileus
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Infections and infestations
Infections and infestations - Other, E. coli bacteremia
|
0.00%
0/25 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Infections and infestations
Infections and infestations - Other, Inflenza A
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Gastrointestinal disorders
Intra-abdominal hemorrhage
|
0.00%
0/25 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Infections and infestations
Joint infection
|
0.00%
0/25 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Investigations
Lipase increased
|
0.00%
0/25 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Infections and infestations
Lung infection
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Nervous system disorders
Memory impairment
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Cardiac disorders
Myocardial infarction
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Gastrointestinal disorders
Nausea
|
4.0%
1/25 • Number of events 3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, Colon Cancer
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Nervous system disorders
Nervous system disorders - Other, Mental status change
|
0.00%
0/25 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Nervous system disorders
Nervous system disorders - Other, Myelitis
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Musculoskeletal and connective tissue disorders
Non-cardiac chest pain
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Nervous system disorders
Paresthesia
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
8.0%
2/25 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Investigations
Serum amylase increased
|
0.00%
0/25 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Skin and subcutaneous tissue disorders
Skin ulceration
|
4.0%
1/25 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Vascular disorders
Thromboembolic event
|
8.0%
2/25 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Reproductive system and breast disorders
Uterine hemorrhage
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Gastrointestinal disorders
Vomiting
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Nervous system disorders
Dysarthia
|
0.00%
0/25 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
Other adverse events
| Measure |
Tyrosine Kinase Inhibitor Naïve Epidermal Growth Factor Receptor *Mutated Non Small Cell Lung Cancer
n=25 participants at risk
COHORT 1: Osimertinib followed by LAT followed by osimertinib. Single daily dose of Osimertinib until progression. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation.
\*including germline T790M mutation
|
EGFR Mutated NSCLC Progressed on Prior 1st/2nd Generation EGFR TKI Therapy &Acquired T790M Mutation
n=9 participants at risk
Cohort 2 - Osimertinib followed by LAT followed by osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on osimertinib: surgery, radiotherapy, or radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
|
Epidermal Growth Factor Receptor Mutated Non Small Cell Lung Cancer Progressed on Osimertinib
n=3 participants at risk
Cohort 3 - LAT followed by Osimertinib. Participants may undergo 1 of 3 local ablative procedures after initial progression on Osimertinib: surgery, radiotherapy, radiofrequency ablation. The starting dose of Osimertinib will be 80 mg per day for participants without leptomeningeal disease and 160 mg per day for those with leptomeningeal disease at baseline. Single daily dose of Osimertinib until progression.
|
|---|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
24.0%
6/25 • Number of events 10 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
33.3%
3/9 • Number of events 3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Investigations
Activated partial thromboplastin time prolonged
|
0.00%
0/25 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Renal and urinary disorders
Acute kidney injury
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Endocrine disorders
Adrenal insufficiency
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Investigations
Alanine aminotransferase increased
|
24.0%
6/25 • Number of events 9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
22.2%
2/9 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
33.3%
1/3 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Investigations
Alkaline phosphatase increased
|
12.0%
3/25 • Number of events 7 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis
|
16.0%
4/25 • Number of events 4 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
16.0%
4/25 • Number of events 4 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Nervous system disorders
Amnesia
|
8.0%
2/25 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Blood and lymphatic system disorders
Anemia
|
16.0%
4/25 • Number of events 23 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
22.2%
2/9 • Number of events 3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Metabolism and nutrition disorders
Anorexia
|
36.0%
9/25 • Number of events 14 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
33.3%
3/9 • Number of events 4 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/25 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Infections and infestations
Appendicitis
|
0.00%
0/25 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
8.0%
2/25 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
22.2%
2/9 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Gastrointestinal disorders
Ascites
|
0.00%
0/25 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Investigations
Aspartate aminotransferase increased
|
24.0%
6/25 • Number of events 9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
33.3%
1/3 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Respiratory, thoracic and mediastinal disorders
Atelectasis
|
8.0%
2/25 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
24.0%
6/25 • Number of events 10 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Gastrointestinal disorders
Bloating
|
20.0%
5/25 • Number of events 5 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Eye disorders
Blurred vision
|
28.0%
7/25 • Number of events 7 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
28.0%
7/25 • Number of events 8 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Infections and infestations
Bronchial infection
|
0.00%
0/25 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Injury, poisoning and procedural complications
Bruising
|
8.0%
2/25 • Number of events 4 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Musculoskeletal and connective tissue disorders
Buttock pain
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Investigations
CPK increased
|
28.0%
7/25 • Number of events 23 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
22.2%
2/9 • Number of events 14 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Cardiac disorders
Cardiac disorders - Other, Atrial premature complex
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Eye disorders
Cataract
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
22.2%
2/9 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Cardiac disorders
Chest pain - cardiac
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
General disorders
Chills
|
12.0%
3/25 • Number of events 3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
33.3%
3/9 • Number of events 4 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Psychiatric disorders
Confusion
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Eye disorders
Conjunctivitis
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Gastrointestinal disorders
Constipation
|
32.0%
8/25 • Number of events 11 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
22.2%
2/9 • Number of events 3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
52.0%
13/25 • Number of events 20 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
22.2%
2/9 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Investigations
Creatinine increased
|
4.0%
1/25 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Metabolism and nutrition disorders
Dehydration
|
8.0%
2/25 • Number of events 3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Gastrointestinal disorders
Dental caries
|
0.00%
0/25 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Gastrointestinal disorders
Diarrhea
|
48.0%
12/25 • Number of events 16 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
66.7%
6/9 • Number of events 10 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Nervous system disorders
Dizziness
|
36.0%
9/25 • Number of events 11 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
44.4%
4/9 • Number of events 4 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Eye disorders
Dry eye
|
20.0%
5/25 • Number of events 7 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
22.2%
2/9 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Gastrointestinal disorders
Dry mouth
|
12.0%
3/25 • Number of events 3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
40.0%
10/25 • Number of events 14 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
22.2%
2/9 • Number of events 4 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
66.7%
2/3 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Nervous system disorders
Dysesthesia
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Nervous system disorders
Dysgeusia
|
12.0%
3/25 • Number of events 3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Gastrointestinal disorders
Dyspepsia
|
16.0%
4/25 • Number of events 4 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Gastrointestinal disorders
Dysphagia
|
12.0%
3/25 • Number of events 3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
48.0%
12/25 • Number of events 19 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
44.4%
4/9 • Number of events 5 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Ear and labyrinth disorders
Ear and labyrinth disorders - Other, Ear plugged
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Ear and labyrinth disorders
Ear and labyrinth disorders - Other, Muffled hearing
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Ear and labyrinth disorders
Ear pain
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
General disorders
Edema face
|
8.0%
2/25 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
General disorders
Edema limbs
|
8.0%
2/25 • Number of events 3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Cardiac disorders
Electrocardiogram QT corrected interval prolonged
|
28.0%
7/25 • Number of events 13 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
77.8%
7/9 • Number of events 20 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
33.3%
1/3 • Number of events 3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
12.0%
3/25 • Number of events 4 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Reproductive system and breast disorders
Erectile dysfunction
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Gastrointestinal disorders
Esophagitis
|
8.0%
2/25 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Eye disorders
Eye disorders - Other, CN 4 palsy
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Eye disorders
Eye disorders - Other, Diplopia
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Eye disorders
Eye pain
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Eye disorders
Eyelid function disorder
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
General disorders
Facial pain
|
0.00%
0/25 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Injury, poisoning and procedural complications
Fall
|
12.0%
3/25 • Number of events 3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
33.3%
1/3 • Number of events 3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
General disorders
Fatigue
|
48.0%
12/25 • Number of events 18 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
44.4%
4/9 • Number of events 8 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Gastrointestinal disorders
Fecal incontinence
|
4.0%
1/25 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
General disorders
Fever
|
16.0%
4/25 • Number of events 9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
22.2%
2/9 • Number of events 4 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Eye disorders
Flashing lights
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Eye disorders
Floaters
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
General disorders
Flu like symptoms
|
8.0%
2/25 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Injury, poisoning and procedural complications
Fracture
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
General disorders
Gait disturbance
|
8.0%
2/25 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Gastrointestinal disorders
Gastritis
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
16.0%
4/25 • Number of events 4 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Gastrointestinal disorders
Gastrointestinal disorders - Other, Abdominal cramps
|
0.00%
0/25 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Gastrointestinal disorders
Gastrointestinal disorders - Other, Gastroenteritis
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Gastrointestinal disorders
Gastrointestinal disorders - Other, Hematemesis
|
0.00%
0/25 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Gastrointestinal disorders
Gastrointestinal disorders - Other, stomatitis
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
22.2%
2/9 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
General disorders
General disorders and administration site conditions - Other, Incision pain
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
General disorders
General disorders and administration site conditions - Other, Loss of balance
|
0.00%
0/25 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
General disorders
General disorders and administration site conditions - Other, Sweating
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Psychiatric disorders
Hallucinations
|
0.00%
0/25 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Nervous system disorders
Headache
|
40.0%
10/25 • Number of events 11 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
44.4%
4/9 • Number of events 4 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Ear and labyrinth disorders
Hearing impaired
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Vascular disorders
Hematoma
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Renal and urinary disorders
Hematuria
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Gastrointestinal disorders
Hemorrhoidal hemorrhage
|
4.0%
1/25 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Gastrointestinal disorders
Hemorrhoids
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Respiratory, thoracic and mediastinal disorders
Hiccups
|
0.00%
0/25 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
0.00%
0/25 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
12.0%
3/25 • Number of events 4 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
8.0%
2/25 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Metabolism and nutrition disorders
Hypermagnesemia
|
4.0%
1/25 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Endocrine disorders
Hyperparathyroidism
|
4.0%
1/25 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Vascular disorders
Hypertension
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Endocrine disorders
Hyperthyroidism
|
0.00%
0/25 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
4.0%
1/25 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Metabolism and nutrition disorders
Hypokalemia
|
24.0%
6/25 • Number of events 8 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
22.2%
2/9 • Number of events 8 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Metabolism and nutrition disorders
Hyponatremia
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
20.0%
5/25 • Number of events 15 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
22.2%
2/9 • Number of events 3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Vascular disorders
Hypotension
|
12.0%
3/25 • Number of events 3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
33.3%
3/9 • Number of events 5 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
8.0%
2/25 • Number of events 3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Infections and infestations
Infections and infestations - Other, COVID-19
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Infections and infestations
Infections and infestations - Other, Left thigh abscess
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Infections and infestations
Infections and infestations - Other, Viral pneumonia
|
0.00%
0/25 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Infections and infestations
Infections and infestations - Other, cold sore
|
0.00%
0/25 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Psychiatric disorders
Insomnia
|
16.0%
4/25 • Number of events 4 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
22.2%
2/9 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Nervous system disorders
Lethargy
|
0.00%
0/25 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Investigations
Lipase increased
|
0.00%
0/25 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
General disorders
Localized edema
|
8.0%
2/25 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Infections and infestations
Lung infection
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Infections and infestations
Lymph gland infection
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Investigations
Lymphocyte count decreased
|
36.0%
9/25 • Number of events 41 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
33.3%
3/9 • Number of events 6 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
66.7%
2/3 • Number of events 4 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Nervous system disorders
Memory impairment
|
12.0%
3/25 • Number of events 5 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Metabolism and nutrition disorders
Metabolism and nutrition disorders - Other, Muscle cramps
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Gastrointestinal disorders
Mucositis oral
|
20.0%
5/25 • Number of events 14 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness lower limb
|
8.0%
2/25 • Number of events 4 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness upper limb
|
8.0%
2/25 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorder - Other, Bilateral leg cramping
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorder - Other, Bilateral calves cramping
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
12.0%
3/25 • Number of events 5 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Skin and subcutaneous tissue disorders
Nail discoloration
|
0.00%
0/25 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Infections and infestations
Nail infection
|
0.00%
0/25 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
22.2%
2/9 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Skin and subcutaneous tissue disorders
Nail loss
|
8.0%
2/25 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
22.2%
2/9 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Skin and subcutaneous tissue disorders
Nail ridging
|
32.0%
8/25 • Number of events 8 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
22.2%
2/9 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
12.0%
3/25 • Number of events 3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Gastrointestinal disorders
Nausea
|
40.0%
10/25 • Number of events 14 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
77.8%
7/9 • Number of events 10 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
8.0%
2/25 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
22.2%
2/9 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Investigations
Neutrophil count decreased
|
24.0%
6/25 • Number of events 33 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 6 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Musculoskeletal and connective tissue disorders
Non-cardiac chest pain
|
32.0%
8/25 • Number of events 9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
44.4%
4/9 • Number of events 4 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Gastrointestinal disorders
Oral pain
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
General disorders
Pain
|
32.0%
8/25 • Number of events 16 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
55.6%
5/9 • Number of events 11 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
28.0%
7/25 • Number of events 8 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
22.2%
2/9 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysesthesia syndrome
|
4.0%
1/25 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Cardiac disorders
Palpitations
|
8.0%
2/25 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Skin and subcutaneous tissue disorders
Papulopustular rash
|
8.0%
2/25 • Number of events 3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Nervous system disorders
Paresthesia
|
32.0%
8/25 • Number of events 9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
33.3%
3/9 • Number of events 4 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Infections and infestations
Paronychia
|
16.0%
4/25 • Number of events 5 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
22.2%
2/9 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Cardiac disorders
Pericardial effusion
|
8.0%
2/25 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
8.0%
2/25 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Eye disorders
Photophobia
|
0.00%
0/25 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
22.2%
2/9 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Investigations
Platelet count decreased
|
28.0%
7/25 • Number of events 13 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
66.7%
2/3 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
16.0%
4/25 • Number of events 9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
44.4%
4/9 • Number of events 5 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.00%
0/25 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
8.0%
2/25 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Respiratory, thoracic and mediastinal disorders
Postnasal drip
|
4.0%
1/25 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
66.7%
2/3 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Nervous system disorders
Presyncope
|
12.0%
3/25 • Number of events 4 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
16.0%
4/25 • Number of events 4 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
22.2%
2/9 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Psychiatric disorders
Psychiatric disorders - Other, Erratic mood
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Psychiatric disorders
Psychiatric disorders - Other, Mental fog
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Skin and subcutaneous tissue disorders
Purpura
|
0.00%
0/25 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Skin and subcutaneous tissue disorders
Rash acneiform
|
24.0%
6/25 • Number of events 8 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
56.0%
14/25 • Number of events 26 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
22.2%
2/9 • Number of events 3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Skin and subcutaneous tissue disorders
Rash pustular
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Gastrointestinal disorders
Rectal hemorrhage
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders - Other, Hemoptysis
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders - Other, Hydropneumothorax
|
4.0%
1/25 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders - Other, Hypoxemic Respiratory Failure
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders - Other, Rhinorrhea
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders - Other, Shingles
|
0.00%
0/25 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders - Other, Subcutaneous emphysema
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders - Other, Tachypnea
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Nervous system disorders
Seizure
|
0.00%
0/25 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
33.3%
1/3 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Investigations
Serum amylase increased
|
0.00%
0/25 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Cardiac disorders
Sinus bradycardia
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Cardiac disorders
Sinus tachycardia
|
20.0%
5/25 • Number of events 7 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Infections and infestations
Sinusitis
|
8.0%
2/25 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - Other, Basal Cell Carcinoma
|
0.00%
0/25 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - Other, Crack right and left thumb and left 3rd finger
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - Other, Cracks around fingertips
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - Other, Skin lacerations
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - Other, mild cracks at fingertips
|
0.00%
0/25 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Skin and subcutaneous tissue disorders
Skin hypopigmentation
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Infections and infestations
Skin infection
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Skin and subcutaneous tissue disorders
Skin ulceration
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Infections and infestations
Soft tissue infection
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Nervous system disorders
Somnolence
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Respiratory, thoracic and mediastinal disorders
Sore throat
|
28.0%
7/25 • Number of events 8 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Infections and infestations
Stoma site infection
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Surgical and medical procedures
Surgical and medical procedures - Other, Incision site pain
|
4.0%
1/25 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Surgical and medical procedures
Surgical and medical procedures - Other, abdominoplasty
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Vascular disorders
Thromboembolic event
|
8.0%
2/25 • Number of events 3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
22.2%
2/9 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Ear and labyrinth disorders
Tinnitus
|
8.0%
2/25 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Gastrointestinal disorders
Toothache
|
0.00%
0/25 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Nervous system disorders
Tremor
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Infections and infestations
Upper respiratory infection
|
24.0%
6/25 • Number of events 7 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
22.2%
2/9 • Number of events 3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Renal and urinary disorders
Urinary incontinence
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Renal and urinary disorders
Urinary retention
|
4.0%
1/25 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Infections and infestations
Urinary tract infection
|
8.0%
2/25 • Number of events 5 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
22.2%
2/9 • Number of events 3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Renal and urinary disorders
Urinary tract pain
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Renal and urinary disorders
Urinary urgency
|
0.00%
0/25 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
4.0%
1/25 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Reproductive system and breast disorders
Uterine hemorrhage
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Reproductive system and breast disorders
Vaginal hemorrhage
|
4.0%
1/25 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/9 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/25 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Gastrointestinal disorders
Vomiting
|
48.0%
12/25 • Number of events 15 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
22.2%
2/9 • Number of events 3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Eye disorders
Watering eyes
|
12.0%
3/25 • Number of events 4 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Investigations
Weight loss
|
40.0%
10/25 • Number of events 19 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
22.2%
2/9 • Number of events 3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
0.00%
0/25 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
11.1%
1/9 • Number of events 3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
0.00%
0/3 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
|
Investigations
White blood cell decreased
|
20.0%
5/25 • Number of events 32 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
22.2%
2/9 • Number of events 2 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
33.3%
1/3 • Number of events 1 • Date treatment consent signed to date off study, approximately 74 months and 16 days, 65 months and 16 days, and 40 months and 4 days for the first, second and third group respectively.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place