Trial Outcomes & Findings for A Phase II Trial to Evaluate the Efficacy of AZD6094 (HMPL-504) in Patients With Papillary Renal Cell Carcinoma (PRCC) (NCT NCT02127710)
NCT ID: NCT02127710
Last Updated: 2021-04-19
Results Overview
The primary outcome measure was Objective Response Rate (ORR), defined as the proportion of patients with either a complete response or a partial response by investigator assessment according to Response Evaluation Criteria for Solid Tumours (RECIST) v1.1.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
111 participants
Primary outcome timeframe
Up to 12 months
Results posted on
2021-04-19
Participant Flow
111 patients were enrolled; 109 patients received at least one dose of AZD6094 administered orally (po). Two patients withdrew prior to receiving any study drug. The study was conducted at 23 international sites in the United States, Canada, United Kingdom and Spain.
All patients were required to provide an archived or fresh tumour sample at enrolment to confirm eligibility, and for performance of the c-MET biomarker analysis. c-MET biomarker results determined the subgroup placement for data analysis as follows: c-MET positive (n=46), c-MET negative (n=47), and c-MET unknown (n=16).
Participant milestones
| Measure |
c-MET Positive [600mg AZD6094 po]
All participants tested for the presence of c-MET mutations
|
c-MET Negative [600mg AZD6094 po]
All participants were tested for the presence of c-MET mutations.
|
c-MET Status Unknown [600mg AZD6094 po]
All participants were tested for the presence of c-MET mutations.
|
|---|---|---|---|
|
Overall Study
STARTED
|
46
|
47
|
16
|
|
Overall Study
COMPLETED
|
46
|
47
|
16
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Phase II Trial to Evaluate the Efficacy of AZD6094 (HMPL-504) in Patients With Papillary Renal Cell Carcinoma (PRCC)
Baseline characteristics by cohort
| Measure |
c-MET Positive [600mg AZD6094 po]
n=46 Participants
All participants tested for the presence of c-MET mutations
|
c-MET Negative [600mg AZD6094 po]
n=47 Participants
All participants were tested for the presence of c-MET mutations.
|
c-MET Status Unknown [600mg AZD6094 po]
n=16 Participants
All participants were tested for the presence of c-MET mutations.
|
Total
n=109 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
|
24 Participants
n=5 Participants
|
26 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
59 Participants
n=4 Participants
|
|
Age, Categorical
>=65 years
|
22 Participants
n=5 Participants
|
21 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
50 Participants
n=4 Participants
|
|
Age, Continuous
|
64 years
n=5 Participants
|
64 years
n=7 Participants
|
61 years
n=5 Participants
|
64 years
n=4 Participants
|
|
Sex: Female, Male
Female
|
13 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
31 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
33 Participants
n=5 Participants
|
36 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
78 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
6 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
14 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
40 Participants
n=5 Participants
|
41 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
95 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
|
|
ECOG Performance Status
PS=0
|
19 Participants
n=5 Participants
|
25 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
51 Participants
n=4 Participants
|
|
ECOG Performance Status
PS=1
|
27 Participants
n=5 Participants
|
22 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
58 Participants
n=4 Participants
|
|
ECOG Performance Status
PS=2
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
ECOG Performance Status
PS=3
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
ECOG Performance Status
PS=4
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
PRCC Confirmation from Central Laboratory
PRCC Not Confirmed
|
9 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
24 Participants
n=4 Participants
|
|
PRCC Confirmation from Central Laboratory
PRCC Confirmed
|
37 Participants
n=5 Participants
|
40 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
85 Participants
n=4 Participants
|
|
Stage Classification
Low
|
1 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
|
Stage Classification
Intermediate
|
8 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
24 Participants
n=4 Participants
|
|
Stage Classification
High
|
13 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
31 Participants
n=4 Participants
|
|
Stage Classification
Missing
|
24 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
49 Participants
n=4 Participants
|
|
Renal Cell Classification
Type I PRCC
|
12 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
16 Participants
n=4 Participants
|
|
Renal Cell Classification
Type II PRCC
|
25 Participants
n=5 Participants
|
38 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
69 Participants
n=4 Participants
|
|
Renal Cell Classification
Unclassified PRCC
|
7 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
14 Participants
n=4 Participants
|
|
Renal Cell Classification
Other
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
|
Renal Cell Classification
Unknown
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
8 Participants
n=4 Participants
|
|
MSKCC Risk Group
Favourable Risk
|
3 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
15 Participants
n=4 Participants
|
|
MSKCC Risk Group
Intermediate Risk
|
28 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
49 Participants
n=4 Participants
|
|
MSKCC Risk Group
Poor Risk
|
3 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
10 Participants
n=4 Participants
|
|
MSKCC Risk Group
Missing
|
12 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
35 Participants
n=4 Participants
|
|
Weight
|
76.5 Kg
n=5 Participants
|
83.5 Kg
n=7 Participants
|
87.65 Kg
n=5 Participants
|
79.5 Kg
n=4 Participants
|
PRIMARY outcome
Timeframe: Up to 12 monthsPopulation: ORR was assessed on the efficacy analysis set, consisting of all patients with measurable disease, PRCC confirmed by a central laboratory and have received at least 1 dose of AZD6094 (n = 85).
The primary outcome measure was Objective Response Rate (ORR), defined as the proportion of patients with either a complete response or a partial response by investigator assessment according to Response Evaluation Criteria for Solid Tumours (RECIST) v1.1.
Outcome measures
| Measure |
Efficacy Analysis Set
n=85 Participants
All patients with measurable disease, PRCC confirmed by central laboratory and received at least 1 dose of study medication
|
Safety Analysis Set
n=109 Participants
All patients who have received at least 1 dose of study medication
|
c-MET Status Unknown [600mg AZD6094 po]
All participants were tested for the presence of c-MET mutations.
|
Total [600mg AZD6094 po]
All participants tested for the presence of c-MET mutations
|
|---|---|---|---|---|
|
Objective Response Rate (RECIST Version 1.1)
Complete Response
|
0 Participants
|
0 Participants
|
—
|
—
|
|
Objective Response Rate (RECIST Version 1.1)
Partial Response
|
3 Participants
|
8 Participants
|
—
|
—
|
|
Objective Response Rate (RECIST Version 1.1)
Stable Disease >= 5 Weeks
|
46 Participants
|
59 Participants
|
—
|
—
|
|
Objective Response Rate (RECIST Version 1.1)
Progression
|
34 Participants
|
40 Participants
|
—
|
—
|
|
Objective Response Rate (RECIST Version 1.1)
Not Evaluable
|
2 Participants
|
2 Participants
|
—
|
—
|
PRIMARY outcome
Timeframe: 12 MonthsPopulation: ORR was assessed on the efficacy analysis set, consisting of all patients with measurable disease, PRCC confirmed by a central laboratory and received at least 1 dose of AZD6094 (n = 85).
The primary outcome measure was ORR, defined as the proportion of patients with either a complete response or a partial response by investigator assessment according to RECIST v1.1.
Outcome measures
| Measure |
Efficacy Analysis Set
n=37 Participants
All patients with measurable disease, PRCC confirmed by central laboratory and received at least 1 dose of study medication
|
Safety Analysis Set
n=40 Participants
All patients who have received at least 1 dose of study medication
|
c-MET Status Unknown [600mg AZD6094 po]
n=8 Participants
All participants were tested for the presence of c-MET mutations.
|
Total [600mg AZD6094 po]
n=85 Participants
All participants tested for the presence of c-MET mutations
|
|---|---|---|---|---|
|
Objective Response Rate (RECIST Version 1.1) Stratified by c-MET Status in Efficacy Analysis Set
Complete Response
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Objective Response Rate (RECIST Version 1.1) Stratified by c-MET Status in Efficacy Analysis Set
Partial Response
|
3 Participants
|
0 Participants
|
0 Participants
|
3 Participants
|
|
Objective Response Rate (RECIST Version 1.1) Stratified by c-MET Status in Efficacy Analysis Set
Stable Disease >= 5 weeks
|
23 Participants
|
19 Participants
|
4 Participants
|
46 Participants
|
|
Objective Response Rate (RECIST Version 1.1) Stratified by c-MET Status in Efficacy Analysis Set
Progression
|
10 Participants
|
20 Participants
|
4 Participants
|
34 Participants
|
|
Objective Response Rate (RECIST Version 1.1) Stratified by c-MET Status in Efficacy Analysis Set
Not Evaluable
|
1 Participants
|
1 Participants
|
0 Participants
|
2 Participants
|
PRIMARY outcome
Timeframe: 12 MonthsPopulation: ORR was assessed on the safety analysis set, consisting of all patients who received at least one dose of the study drug (n = 109).
The primary outcome measure was ORR, defined as the proportion of patients with either a confirmed complete response/partial response by investigator assessment according to RECIST v1.1.
Outcome measures
| Measure |
Efficacy Analysis Set
n=46 Participants
All patients with measurable disease, PRCC confirmed by central laboratory and received at least 1 dose of study medication
|
Safety Analysis Set
n=47 Participants
All patients who have received at least 1 dose of study medication
|
c-MET Status Unknown [600mg AZD6094 po]
n=16 Participants
All participants were tested for the presence of c-MET mutations.
|
Total [600mg AZD6094 po]
n=109 Participants
All participants tested for the presence of c-MET mutations
|
|---|---|---|---|---|
|
Objective Response Rate (RECIST Version 1.1) Stratified by c-MET Status in Safety Analysis Set
Progression
|
10 Participants
|
25 Participants
|
5 Participants
|
40 Participants
|
|
Objective Response Rate (RECIST Version 1.1) Stratified by c-MET Status in Safety Analysis Set
Not Evaluable
|
1 Participants
|
1 Participants
|
0 Participants
|
2 Participants
|
|
Objective Response Rate (RECIST Version 1.1) Stratified by c-MET Status in Safety Analysis Set
Complete Response
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Objective Response Rate (RECIST Version 1.1) Stratified by c-MET Status in Safety Analysis Set
Partial Response
|
8 Participants
|
0 Participants
|
0 Participants
|
8 Participants
|
|
Objective Response Rate (RECIST Version 1.1) Stratified by c-MET Status in Safety Analysis Set
Stable Disease >= 5 weeks
|
27 Participants
|
21 Participants
|
11 Participants
|
59 Participants
|
SECONDARY outcome
Timeframe: Up to 12 monthsOutcome measures
| Measure |
Efficacy Analysis Set
n=37 Participants
All patients with measurable disease, PRCC confirmed by central laboratory and received at least 1 dose of study medication
|
Safety Analysis Set
n=40 Participants
All patients who have received at least 1 dose of study medication
|
c-MET Status Unknown [600mg AZD6094 po]
n=8 Participants
All participants were tested for the presence of c-MET mutations.
|
Total [600mg AZD6094 po]
All participants tested for the presence of c-MET mutations
|
|---|---|---|---|---|
|
Progression Free Survival Stratified by c-MET Status in the Efficacy Analysis Set
|
18.3 Weeks
Interval 12.3 to 35.4
|
9.7 Weeks
Interval 6.1 to 12.4
|
6.1 Weeks
Interval 5.1 to
Due to insufficient number of events, the upper limit of the 95% CI for median PFS was not calculable.
|
—
|
SECONDARY outcome
Timeframe: Up to 12 monthsOutcome measures
| Measure |
Efficacy Analysis Set
n=37 Participants
All patients with measurable disease, PRCC confirmed by central laboratory and received at least 1 dose of study medication
|
Safety Analysis Set
n=40 Participants
All patients who have received at least 1 dose of study medication
|
c-MET Status Unknown [600mg AZD6094 po]
n=8 Participants
All participants were tested for the presence of c-MET mutations.
|
Total [600mg AZD6094 po]
All participants tested for the presence of c-MET mutations
|
|---|---|---|---|---|
|
Overall Survival Stratified by c-MET Status in the Efficacy Analysis Set
|
NA Weeks
Interval 34.6 to
As the sufficient number of events was not reached at the time of data cut-off, the median OS and the upper limit of the 95% CI for median OS were not calculable.
|
61.1 Weeks
Interval 29.4 to
Due to insufficient number of events, the upper limit of the 95% CI for median OS was not calculable.
|
51.5 Weeks
Interval 8.1 to
Due to insufficient number of events, the upper limit of the 95% CI for median OS was not calculable.
|
—
|
SECONDARY outcome
Timeframe: Up to 12 monthsOutcome measures
| Measure |
Efficacy Analysis Set
n=46 Participants
All patients with measurable disease, PRCC confirmed by central laboratory and received at least 1 dose of study medication
|
Safety Analysis Set
n=47 Participants
All patients who have received at least 1 dose of study medication
|
c-MET Status Unknown [600mg AZD6094 po]
n=16 Participants
All participants were tested for the presence of c-MET mutations.
|
Total [600mg AZD6094 po]
All participants tested for the presence of c-MET mutations
|
|---|---|---|---|---|
|
Progression Free Survival Stratified by c-MET Status in the Safety Analysis Set
|
24.7 Weeks
Interval 17.7 to 35.4
|
6.6 Weeks
Interval 6.1 to 11.9
|
12.1 Weeks
Interval 6.1 to 41.9
|
—
|
SECONDARY outcome
Timeframe: Up to 12 monthsOutcome measures
| Measure |
Efficacy Analysis Set
n=46 Participants
All patients with measurable disease, PRCC confirmed by central laboratory and received at least 1 dose of study medication
|
Safety Analysis Set
n=47 Participants
All patients who have received at least 1 dose of study medication
|
c-MET Status Unknown [600mg AZD6094 po]
n=16 Participants
All participants were tested for the presence of c-MET mutations.
|
Total [600mg AZD6094 po]
All participants tested for the presence of c-MET mutations
|
|---|---|---|---|---|
|
Overall Survival Stratified by c-MET Status in the Safety Analysis Set
|
NA Weeks
Interval 42.9 to
As the sufficient number of events was not reached at the time of data cut-off, the median OS and the upper limit of the 95% CI for median OS were not calculable.
|
61.1 Weeks
Interval 40.6 to 106.7
|
54.9 Weeks
Interval 18.4 to
Due to insufficient number of events, the upper limit of the 95% CI for median OS was not calculable.
|
—
|
SECONDARY outcome
Timeframe: 12 Weeks (at 12 weeks timepoint)12 week summary for patients in the Efficacy analysis set, by MET status. The numbers of patients analysed represent the numbers evaluable at the 12 week timepoint.
Outcome measures
| Measure |
Efficacy Analysis Set
n=22 Participants
All patients with measurable disease, PRCC confirmed by central laboratory and received at least 1 dose of study medication
|
Safety Analysis Set
n=14 Participants
All patients who have received at least 1 dose of study medication
|
c-MET Status Unknown [600mg AZD6094 po]
n=1 Participants
All participants were tested for the presence of c-MET mutations.
|
Total [600mg AZD6094 po]
All participants tested for the presence of c-MET mutations
|
|---|---|---|---|---|
|
Change From Baseline in Target Lesion Tumour Size at 12 Weeks in Efficacy Analysis Set
|
-6.3 Percent change
Standard Deviation 21.56
|
3.4 Percent change
Standard Deviation 20.05
|
7.1 Percent change
Standard Deviation 0
|
—
|
SECONDARY outcome
Timeframe: 12 Weeks (at 12 week timepoint)12 week summary for patients in the Safety analysis set by MET Status. The number of patients analysed represent the number of evaluable patients at the 12 week timepoint.
Outcome measures
| Measure |
Efficacy Analysis Set
n=30 Participants
All patients with measurable disease, PRCC confirmed by central laboratory and received at least 1 dose of study medication
|
Safety Analysis Set
n=16 Participants
All patients who have received at least 1 dose of study medication
|
c-MET Status Unknown [600mg AZD6094 po]
n=6 Participants
All participants were tested for the presence of c-MET mutations.
|
Total [600mg AZD6094 po]
All participants tested for the presence of c-MET mutations
|
|---|---|---|---|---|
|
Change From Baseline in Target Lesion Tumour Size at 12 Weeks in Safety Analysis Set.
|
-10.9 Percent change
Standard Deviation 21.39
|
4.3 Percent change
Standard Deviation 18.96
|
5.1 Percent change
Standard Deviation 17.41
|
—
|
SECONDARY outcome
Timeframe: Up to 12 monthsDuration of Response is the time from the first documentation of confirmed complete response/partial response until the date of progression, or death in the absence of progression. There were 8 responders: one of whom subsequently progressed or died and seven of whom were still classified as responders at the time of data cut-off and were therefore censored. It was not possible to determine a median or 75th percentile.
Outcome measures
| Measure |
Efficacy Analysis Set
n=109 Participants
All patients with measurable disease, PRCC confirmed by central laboratory and received at least 1 dose of study medication
|
Safety Analysis Set
All patients who have received at least 1 dose of study medication
|
c-MET Status Unknown [600mg AZD6094 po]
All participants were tested for the presence of c-MET mutations.
|
Total [600mg AZD6094 po]
All participants tested for the presence of c-MET mutations
|
|---|---|---|---|---|
|
Duration of Response
|
NA Weeks
Interval 18.1 to
The median DoR and 75th percentile for DoR were not calculable within the timeframe of this study.
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 24 HoursThe number of patients analysed represent the number of patients with evaluable PK parameters for this endpoint.
Outcome measures
| Measure |
Efficacy Analysis Set
n=53 Participants
All patients with measurable disease, PRCC confirmed by central laboratory and received at least 1 dose of study medication
|
Safety Analysis Set
All patients who have received at least 1 dose of study medication
|
c-MET Status Unknown [600mg AZD6094 po]
All participants were tested for the presence of c-MET mutations.
|
Total [600mg AZD6094 po]
All participants tested for the presence of c-MET mutations
|
|---|---|---|---|---|
|
Peak Plasma Concentration of AZD6094 Following Single Dose
|
3038.8984 ng/mL
Geometric Coefficient of Variation 44.4184
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 24 HoursThe number of patients analysed represent the number of patients with evaluable PK parameters for this endpoint.
Outcome measures
| Measure |
Efficacy Analysis Set
n=53 Participants
All patients with measurable disease, PRCC confirmed by central laboratory and received at least 1 dose of study medication
|
Safety Analysis Set
All patients who have received at least 1 dose of study medication
|
c-MET Status Unknown [600mg AZD6094 po]
All participants were tested for the presence of c-MET mutations.
|
Total [600mg AZD6094 po]
All participants tested for the presence of c-MET mutations
|
|---|---|---|---|---|
|
Time to Peak Plasma Concentration of AZD6094 After Single Dose
|
2.0 Hours
Interval 0.5 to 8.0
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 24 HoursThe number of patients analysed represent the number of patients with evaluable PK parameters for this endpoint.
Outcome measures
| Measure |
Efficacy Analysis Set
n=19 Participants
All patients with measurable disease, PRCC confirmed by central laboratory and received at least 1 dose of study medication
|
Safety Analysis Set
All patients who have received at least 1 dose of study medication
|
c-MET Status Unknown [600mg AZD6094 po]
All participants were tested for the presence of c-MET mutations.
|
Total [600mg AZD6094 po]
All participants tested for the presence of c-MET mutations
|
|---|---|---|---|---|
|
Apparent Volume of Distribution of AZD6094 Following Single Dose
|
137.4237 Liters
Standard Deviation 36.5971
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 24 HoursThe number of patients analysed represent the number of patients with evaluable PK parameters for this endpoint.
Outcome measures
| Measure |
Efficacy Analysis Set
n=19 Participants
All patients with measurable disease, PRCC confirmed by central laboratory and received at least 1 dose of study medication
|
Safety Analysis Set
All patients who have received at least 1 dose of study medication
|
c-MET Status Unknown [600mg AZD6094 po]
All participants were tested for the presence of c-MET mutations.
|
Total [600mg AZD6094 po]
All participants tested for the presence of c-MET mutations
|
|---|---|---|---|---|
|
Area Under Plasma Concentration Time Curve for AZD6094 After Single Dose
|
13144.7381 h*ng/mL
Geometric Coefficient of Variation 36.4328
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 24 HoursThe number of patients analysed represent the number of patients with evaluable PK parameters for this endpoint.
Outcome measures
| Measure |
Efficacy Analysis Set
n=53 Participants
All patients with measurable disease, PRCC confirmed by central laboratory and received at least 1 dose of study medication
|
Safety Analysis Set
All patients who have received at least 1 dose of study medication
|
c-MET Status Unknown [600mg AZD6094 po]
All participants were tested for the presence of c-MET mutations.
|
Total [600mg AZD6094 po]
All participants tested for the presence of c-MET mutations
|
|---|---|---|---|---|
|
Area Under Plasma Concentration Time Curve for AZD6094 After Single Dose (Time Zero to Last Measurement)
|
13214.2441 h*ng/mL
Geometric Coefficient of Variation 46.4616
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 24 HoursThe number of patients analysed represent the number of patients with evaluable PK parameters for this endpoint.
Outcome measures
| Measure |
Efficacy Analysis Set
n=19 Participants
All patients with measurable disease, PRCC confirmed by central laboratory and received at least 1 dose of study medication
|
Safety Analysis Set
All patients who have received at least 1 dose of study medication
|
c-MET Status Unknown [600mg AZD6094 po]
All participants were tested for the presence of c-MET mutations.
|
Total [600mg AZD6094 po]
All participants tested for the presence of c-MET mutations
|
|---|---|---|---|---|
|
Apparent Total Clearance of AZD6094 From Plasma After Single Dose
|
48.4938 L/hour
Standard Deviation 17.3386
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 24 HoursThe number of patients analysed represent the number of evaluable PK parameters for this endpoint.
Outcome measures
| Measure |
Efficacy Analysis Set
n=19 Participants
All patients with measurable disease, PRCC confirmed by central laboratory and received at least 1 dose of study medication
|
Safety Analysis Set
All patients who have received at least 1 dose of study medication
|
c-MET Status Unknown [600mg AZD6094 po]
All participants were tested for the presence of c-MET mutations.
|
Total [600mg AZD6094 po]
All participants tested for the presence of c-MET mutations
|
|---|---|---|---|---|
|
Mean Residence Time of AZD6094 After Single Dose
|
3.9837 Hours
Standard Deviation 0.4813
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 24 HoursThe number of patients analysed represent the number of patients with evaluable PK parameters for this endpoint.
Outcome measures
| Measure |
Efficacy Analysis Set
n=19 Participants
All patients with measurable disease, PRCC confirmed by central laboratory and received at least 1 dose of study medication
|
Safety Analysis Set
All patients who have received at least 1 dose of study medication
|
c-MET Status Unknown [600mg AZD6094 po]
All participants were tested for the presence of c-MET mutations.
|
Total [600mg AZD6094 po]
All participants tested for the presence of c-MET mutations
|
|---|---|---|---|---|
|
Elimination Half-Life of AZD6094 After Single Dose
|
2.0499 Hours
Standard Deviation 0.3820
|
—
|
—
|
—
|
Adverse Events
AZD6094 600 mg Per Day Orally
Serious events: 27 serious events
Other events: 107 other events
Deaths: 57 deaths
Serious adverse events
| Measure |
AZD6094 600 mg Per Day Orally
n=109 participants at risk
All patients who received at least one dose of study medication
|
|---|---|
|
Gastrointestinal disorders
Abdominal incarcerated hernia
|
0.92%
1/109 • Up to 12 months
|
|
Gastrointestinal disorders
Abdominal pain
|
0.92%
1/109 • Up to 12 months
|
|
Renal and urinary disorders
Acute kidney injury
|
3.7%
4/109 • Up to 12 months
|
|
Endocrine disorders
Adrenal insufficiency
|
0.92%
1/109 • Up to 12 months
|
|
Blood and lymphatic system disorders
Anaemia
|
2.8%
3/109 • Up to 12 months
|
|
Gastrointestinal disorders
Ascites
|
1.8%
2/109 • Up to 12 months
|
|
Infections and infestations
Cellulitis
|
0.92%
1/109 • Up to 12 months
|
|
Hepatobiliary disorders
Cholecystitis
|
0.92%
1/109 • Up to 12 months
|
|
Gastrointestinal disorders
Constipation
|
1.8%
2/109 • Up to 12 months
|
|
Metabolism and nutrition disorders
Dehydration
|
0.92%
1/109 • Up to 12 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.92%
1/109 • Up to 12 months
|
|
Nervous system disorders
Hepatic encephalopathy
|
0.92%
1/109 • Up to 12 months
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
0.92%
1/109 • Up to 12 months
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.92%
1/109 • Up to 12 months
|
|
Infections and infestations
Lung Infection
|
0.92%
1/109 • Up to 12 months
|
|
Gastrointestinal disorders
Nausea
|
0.92%
1/109 • Up to 12 months
|
|
General disorders
Pain
|
0.92%
1/109 • Up to 12 months
|
|
Cardiac disorders
Pericarditis
|
0.92%
1/109 • Up to 12 months
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.92%
1/109 • Up to 12 months
|
|
Infections and infestations
Pneumonia
|
0.92%
1/109 • Up to 12 months
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.92%
1/109 • Up to 12 months
|
|
Infections and infestations
Sepsis
|
0.92%
1/109 • Up to 12 months
|
|
Investigations
Transaminases increased
|
0.92%
1/109 • Up to 12 months
|
|
Infections and infestations
Urinary tract infection
|
0.92%
1/109 • Up to 12 months
|
|
Gastrointestinal disorders
Vomiting
|
0.92%
1/109 • Up to 12 months
|
|
Infections and infestations
Wound infection
|
0.92%
1/109 • Up to 12 months
|
|
Hepatobiliary disorders
Drug-induced Liver Injury
|
0.92%
1/109 • Up to 12 months
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary Embolism
|
0.92%
1/109 • Up to 12 months
|
|
Nervous system disorders
Loss of Consciousness
|
0.92%
1/109 • Up to 12 months
|
|
General disorders
Oedema
|
0.92%
1/109 • Up to 12 months
|
|
Cardiac disorders
Myocardial Infaction
|
0.92%
1/109 • Up to 12 months
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.92%
1/109 • Up to 12 months
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
0.92%
1/109 • Up to 12 months
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Rectal cancer
|
0.92%
1/109 • Up to 12 months
|
|
Psychiatric disorders
Confusional state
|
0.92%
1/109 • Up to 12 months
|
|
Vascular disorders
Embolism
|
0.92%
1/109 • Up to 12 months
|
Other adverse events
| Measure |
AZD6094 600 mg Per Day Orally
n=109 participants at risk
All patients who received at least one dose of study medication
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
15.6%
17/109 • Up to 12 months
|
|
Gastrointestinal disorders
Nausea
|
51.4%
56/109 • Up to 12 months
|
|
Gastrointestinal disorders
Vomiting
|
31.2%
34/109 • Up to 12 months
|
|
Gastrointestinal disorders
Constipation
|
26.6%
29/109 • Up to 12 months
|
|
Gastrointestinal disorders
Diarrhoea
|
16.5%
18/109 • Up to 12 months
|
|
Gastrointestinal disorders
Abdominal pain
|
8.3%
9/109 • Up to 12 months
|
|
Gastrointestinal disorders
Abdominal distension
|
5.5%
6/109 • Up to 12 months
|
|
Gastrointestinal disorders
Stomatitis
|
5.5%
6/109 • Up to 12 months
|
|
General disorders
Fatigue
|
45.0%
49/109 • Up to 12 months
|
|
General disorders
Peripheral oedema
|
32.1%
35/109 • Up to 12 months
|
|
General disorders
Asthenia
|
7.3%
8/109 • Up to 12 months
|
|
General disorders
Oedema
|
7.3%
8/109 • Up to 12 months
|
|
General disorders
Chest pain
|
6.4%
7/109 • Up to 12 months
|
|
General disorders
Mucosal inflammation
|
5.5%
6/109 • Up to 12 months
|
|
Investigations
Blood creatinine increased
|
16.5%
18/109 • Up to 12 months
|
|
Investigations
Aspartate aminotransferase increased
|
13.8%
15/109 • Up to 12 months
|
|
Investigations
Weight decreased
|
12.8%
14/109 • Up to 12 months
|
|
Investigations
Alanine aminotransferase increased
|
11.0%
12/109 • Up to 12 months
|
|
Investigations
Weight increased
|
7.3%
8/109 • Up to 12 months
|
|
Investigations
Blood alklaine phosphatase increased
|
6.4%
7/109 • Up to 12 months
|
|
Metabolism and nutrition disorders
Decreased appetite
|
22.9%
25/109 • Up to 12 months
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
11.9%
13/109 • Up to 12 months
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
7.3%
8/109 • Up to 12 months
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
6.4%
7/109 • Up to 12 months
|
|
Metabolism and nutrition disorders
Hyponatremia
|
7.3%
8/109 • Up to 12 months
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
14.7%
16/109 • Up to 12 months
|
|
Musculoskeletal and connective tissue disorders
Arthalgia
|
11.9%
13/109 • Up to 12 months
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
8.3%
9/109 • Up to 12 months
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
10.1%
11/109 • Up to 12 months
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
8.3%
9/109 • Up to 12 months
|
|
Nervous system disorders
Dizziness
|
10.1%
11/109 • Up to 12 months
|
|
Nervous system disorders
Dysgeusia
|
8.3%
9/109 • Up to 12 months
|
|
Nervous system disorders
Headache
|
7.3%
8/109 • Up to 12 months
|
|
Renal and urinary disorders
Proteinuria
|
10.1%
11/109 • Up to 12 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
14.7%
16/109 • Up to 12 months
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
14.7%
16/109 • Up to 12 months
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
10.1%
11/109 • Up to 12 months
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
9.2%
10/109 • Up to 12 months
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
5.5%
6/109 • Up to 12 months
|
|
Musculoskeletal and connective tissue disorders
Muscle spasm
|
6.4%
7/109 • Up to 12 months
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
5.5%
6/109 • Up to 12 months
|
|
Respiratory, thoracic and mediastinal disorders
Pleural Effusion
|
4.6%
5/109 • Up to 12 months
|
|
General disorders
Pain
|
4.6%
5/109 • Up to 12 months
|
|
General disorders
Chills
|
4.6%
5/109 • Up to 12 months
|
|
General disorders
Pyrexia
|
4.6%
5/109 • Up to 12 months
|
|
Metabolism and nutrition disorders
Fluid retention
|
4.6%
5/109 • Up to 12 months
|
|
Gastrointestinal disorders
Ascites
|
4.6%
5/109 • Up to 12 months
|
|
Psychiatric disorders
Insomnia
|
4.6%
5/109 • Up to 12 months
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
4.6%
5/109 • Up to 12 months
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
4.6%
5/109 • Up to 12 months
|
|
Vascular disorders
Hypertension
|
4.6%
5/109 • Up to 12 months
|
|
Vascular disorders
Hypotension
|
4.6%
5/109 • Up to 12 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place