Papillary Renal Cell Cancer
Conditions
Keywords
AZD6094, Savolitinib, Papillary Renal Cell Cancer
Brief summary
This is an open-label, single-arm, multicentre, global, phase II study designed to evaluate the efficacy and safety of AZD6094 in patients with papillary renal cell carcinoma (PRCC) who are treatment naïve or previously treated. An independent central pathology review of tumour samples will be used to confirm the diagnosis of PRCC of all patients enrolling. However, locally available pathology results confirming PRCC will be allowed for timely study entry.
Detailed description
The study will comprise two stages. In Stage 1 approximately 20 patients will be enrolled. This group is considered sufficient to provide preliminary assessment of the anti-tumour activity of AZD6094 in the form of non-binding futility analysis. If ≤ 2 tumour responses are observed in the first 20 evaluable patients termination of the study will be considered taking into account the relevant molecular profile of the patients and additional information from related studies in the drug development programme. All patients entering the study will take AZD6094 600 mg by mouth (PO) once daily (QD). Treatment will be given continuously. Following the baseline assessment, efficacy will be assessed by objective tumour assessments every 6 weeks (±7 days), for the first 12 months and every 12 weeks thereafter until objective disease progression as defined by RECIST v1.1 There will be a data cut-off after all patients have completed at least 12 weeks of treatment with AZD6094 or withdrawn. The database will be locked and data analysis will be performed on this dataset. Any patients still receiving study drug at the time of data cut-off will be able to continue to receive AZD6094 while deriving clinical benefit. Such patients will continue to be monitored for the occurrence of serious adverse events up to 28 days after the last dose of AZD6094. After database lock (DBL) tumour assessments will be performed every 12 weeks (±7 days) until objective disease progression as defined by RECIST v1.1. Patients discontinuing treatment due to documented disease progression will enter a survival follow-up period, where they will be followed for the initiation of subsequent anti-cancer therapies every 3 months until death, loss to follow-up or withdrawal of consent, whichever comes first. Patients discontinuing treatment prior to documented disease progression will enter a progression-free survival follow-up period where they will continue to have disease assessments every 6 weeks (±7 days) for the first 12 months of follow-up and every 12 weeks thereafter until objective disease progression as defined by RECIST v1.1, death, loss to follow-up or withdrawal of consent, whichever comes first. After DBL, tumour assessments will be performed in the progression free survival patient population every 12 weeks (±7 days) until objective disease progression as defined by RECIST v1.1
Interventions
DRUGAZD6094
AZD6094 is a potent and selective small molecule mesenchymal epithelial transition (c-MET) kinase inhibitor.
Sponsors
SCRI Development Innovations, LLC
AstraZeneca
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
1. Provision of informed consent prior to any study specific procedures, sampling and analyses. 2. Histologically confirmed PRCC, which is locally advanced or metastatic. 3. Availability of an archival tumor sample or a pre-treatment fresh tumor sample for confirmation of PRCC by a central laboratory and other biomarker 4. Treatment naïve or have failed on previous treatment for PRCC. Previous treatments may include: targeted therapy (i.e. sunitinib, sorafenib, bevacizumab, pazopanib, temsirolimus, and everolimus), traditional immunotherapy (i.e. interferon-a, Interleukin-2), chemotherapy or a combination of chemoimmunotherapy. 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 6. At least one lesion, not previously irradiated, and not chosen for a biopsy if performed during the screening period that can be accurately measured at baseline and which is suitable for accurate repeated measurements. 7. Adequate hematological function defined as: 1. Absolute neutrophil count ≥1500/μL 2. Haemoglobin ≥9 g/dL 3. Platelets ≥100,000/μL 8. Adequate liver function defined as: 1. Alanine aminotransferase and aspartate aminotransferase ≤2.5 x the upper limit of normal (ULN) 2. Total bilirubin ≤1.5 x ULN 9. Adequate renal function defined as glomerular filtration rate ≥ 40 mL/min, 10. Adequate coagulation parameters, defined as International Normalisation Ratio \<1.5 x ULN or activated partial thromboplastin time \<1.5 x ULN. 11. Patients with known tumor thrombus or deep vein thrombosis are eligible if stable on low molecular weight heparin for ≥4 weeks. 12. Females should be using adequate contraceptive measures should not be breast feeding, and must have a negative pregnancy test prior to start of dosing if of childbearing potential or must have evidence of non-childbearing potential 13. Male patients should be willing to use barrier contraception, i.e. condoms. 14. Ability to swallow and retain oral medications. 15. Predicted life expectancy ≥12 weeks. 16. Aged at least 18 years. 17. Willingness and ability to comply with study and follow-up procedures. 18. Ability to understand the nature of this study and give written informed consent.
Exclusion criteria
1. Most recent chemotherapy, immunotherapy, chemo-immunotherapy, or investigational agents \<21 days of the first dose of study treatment. Most recent targeted therapy \<14 days of the first dose of study treatment. 2. Unresolved toxicities from any prior therapy greater than Common Terminology Criteria for Adverse Events Grade 1 at the time of starting study treatment with the exception of alopecia. 3. Prior or current treatment with a cMet inhibitor 4. Strong inducers or inhibitors of cytochrome P450 3A4 (CYP3A4), strong inhibitors of cytochrome P450 1A2 (CYP1A2), or CYP3A4 substrates with a narrow therapeutic range within 2 weeks before the first dose of study treatment (3 weeks for St John's Wort) 5. Wide field radiotherapy (including therapeutic radioisotopes such as strontium-89) administered ≤28 days or limited field radiation for palliation ≤7 days prior to starting study drug or has not recovered from side effects of such therapy 6. Major surgical procedures ≤28 days of beginning study drug or minor surgical procedures ≤7 days. No waiting is required following port-a-cath placement. 7. Previously untreated brain metastases. 8. Current leptomeningeal metastases or spinal cord compression due to disease. 9. Acute or chronic liver or pancreatic disease. 10. Uncontrolled diabetes mellitus. 11. Gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of oral therapy 12. Any of the following cardiac diseases currently or within the last 6 months: 1. Unstable angina pectoris 2. Congestive heart failure (New York Heart Association ≥ Grade 2) 3. Acute myocardial infarction 4. Stroke or transient ischemic attack 13. Inadequately controlled hypertension (i.e., systolic blood pressure \>160 mmHg or diastolic blood pressure \>100 mmHg) (patients with values above these levels must have their blood pressure controlled with medication prior to starting treatment). 14. Mean resting correct QT interval (QTc) \>470 msec obtained from triplicate electrocardiagrams 15. Any clinically important abnormalities in rhythm, conduction or morphology of resting electrocardiograms, e.g. complete left bundle branch block, third degree heart block, second degree heart block, PR interval \>250 msec. 16. Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital or familial long QT syndrome or family history of unexplained sudden death under 40 years of age or any concomitant medications known to prolong QT interval. 17. Currently receiving treatment with therapeutic doses of warfarin sodium. Low molecular weight heparin is allowed. 18. Serious active infection at the time of treatment, or another serious underlying medical condition that would impair the ability of the patient to receive protocol treatment. 19. Known diagnosis of human immunodeficiency virus, hepatitis B, or hepatitis C. 20. Presence of other active cancers, or history of treatment for invasive cancer ≤5years. Patients with Stage I cancer who have received definitive local treatment at least 3 years previously, and are considered unlikely to recur are eligible. All patients with previously treated in situ carcinoma (i.e., non-invasive) are eligible, as are patients with history of non-melanoma skin cancer. 21. Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (RECIST Version 1.1) | Up to 12 months | 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. |
| Objective Response Rate (RECIST Version 1.1) Stratified by c-MET Status in Efficacy Analysis Set | 12 Months | 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. |
| Objective Response Rate (RECIST Version 1.1) Stratified by c-MET Status in Safety Analysis Set | 12 Months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival Stratified by c-MET Status in the Safety Analysis Set | Up to 12 months | — |
| Change From Baseline in Target Lesion Tumour Size at 12 Weeks in Efficacy Analysis Set | 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. |
| Change From Baseline in Target Lesion Tumour Size at 12 Weeks in Safety Analysis Set. | 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. |
| Duration of Response | Up to 12 months | Duration 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. |
| Peak Plasma Concentration of AZD6094 Following Single Dose | 24 Hours | The number of patients analysed represent the number of patients with evaluable PK parameters for this endpoint. |
| Time to Peak Plasma Concentration of AZD6094 After Single Dose | 24 Hours | The number of patients analysed represent the number of patients with evaluable PK parameters for this endpoint. |
| Progression Free Survival Stratified by c-MET Status in the Efficacy Analysis Set | Up to 12 months | — |
| Area Under Plasma Concentration Time Curve for AZD6094 After Single Dose | 24 Hours | The number of patients analysed represent the number of patients with evaluable PK parameters for this endpoint. |
| Area Under Plasma Concentration Time Curve for AZD6094 After Single Dose (Time Zero to Last Measurement) | 24 Hours | The number of patients analysed represent the number of patients with evaluable PK parameters for this endpoint. |
| Apparent Total Clearance of AZD6094 From Plasma After Single Dose | 24 Hours | The number of patients analysed represent the number of patients with evaluable PK parameters for this endpoint. |
| Mean Residence Time of AZD6094 After Single Dose | 24 Hours | The number of patients analysed represent the number of evaluable PK parameters for this endpoint. |
| Elimination Half-Life of AZD6094 After Single Dose | 24 Hours | The number of patients analysed represent the number of patients with evaluable PK parameters for this endpoint. |
| Apparent Volume of Distribution of AZD6094 Following Single Dose | 24 Hours | The number of patients analysed represent the number of patients with evaluable PK parameters for this endpoint. |
| Overall Survival Stratified by c-MET Status in the Efficacy Analysis Set | Up to 12 months | — |
| Progression Free Survival Stratified by c-MET Status in the Safety Analysis Set | Up to 12 months | — |
Countries
Canada, Spain, United Kingdom, United States
Participant flow
Recruitment details
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.
Pre-assignment details
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).
Participants by arm
| Arm | Count |
|---|---|
| c-MET Positive [600mg AZD6094 po] All participants tested for the presence of c-MET mutations | 46 |
| c-MET Negative [600mg AZD6094 po] All participants were tested for the presence of c-MET mutations. | 47 |
| c-MET Status Unknown [600mg AZD6094 po] All participants were tested for the presence of c-MET mutations. | 16 |
| Total | 109 |
Baseline characteristics
| Characteristic | Total | c-MET Status Unknown [600mg AZD6094 po] | c-MET Positive [600mg AZD6094 po] | c-MET Negative [600mg AZD6094 po] |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 50 Participants | 7 Participants | 22 Participants | 21 Participants |
| Age, Categorical Between 18 and 65 years | 59 Participants | 9 Participants | 24 Participants | 26 Participants |
| Age, Continuous | 64 years | 61 years | 64 years | 64 years |
| ECOG Performance Status PS=0 | 51 Participants | 7 Participants | 19 Participants | 25 Participants |
| ECOG Performance Status PS=1 | 58 Participants | 9 Participants | 27 Participants | 22 Participants |
| ECOG Performance Status PS=2 | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| ECOG Performance Status PS=3 | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| ECOG Performance Status PS=4 | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 14 Participants | 2 Participants | 6 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 95 Participants | 14 Participants | 40 Participants | 41 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| MSKCC Risk Group Favourable Risk | 15 Participants | 2 Participants | 3 Participants | 10 Participants |
| MSKCC Risk Group Intermediate Risk | 49 Participants | 7 Participants | 28 Participants | 14 Participants |
| MSKCC Risk Group Missing | 35 Participants | 5 Participants | 12 Participants | 18 Participants |
| MSKCC Risk Group Poor Risk | 10 Participants | 2 Participants | 3 Participants | 5 Participants |
| PRCC Confirmation from Central Laboratory PRCC Confirmed | 85 Participants | 8 Participants | 37 Participants | 40 Participants |
| PRCC Confirmation from Central Laboratory PRCC Not Confirmed | 24 Participants | 8 Participants | 9 Participants | 7 Participants |
| Renal Cell Classification Other | 2 Participants | 1 Participants | 0 Participants | 1 Participants |
| Renal Cell Classification Type II PRCC | 69 Participants | 6 Participants | 25 Participants | 38 Participants |
| Renal Cell Classification Type I PRCC | 16 Participants | 2 Participants | 12 Participants | 2 Participants |
| Renal Cell Classification Unclassified PRCC | 14 Participants | 2 Participants | 7 Participants | 5 Participants |
| Renal Cell Classification Unknown | 8 Participants | 5 Participants | 2 Participants | 1 Participants |
| Sex: Female, Male Female | 31 Participants | 7 Participants | 13 Participants | 11 Participants |
| Sex: Female, Male Male | 78 Participants | 9 Participants | 33 Participants | 36 Participants |
| Stage Classification High | 31 Participants | 3 Participants | 13 Participants | 15 Participants |
| Stage Classification Intermediate | 24 Participants | 4 Participants | 8 Participants | 12 Participants |
| Stage Classification Low | 5 Participants | 0 Participants | 1 Participants | 4 Participants |
| Stage Classification Missing | 49 Participants | 9 Participants | 24 Participants | 16 Participants |
| Weight | 79.5 Kg | 87.65 Kg | 76.5 Kg | 83.5 Kg |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 57 / 109 |
| other Total, other adverse events | 107 / 109 |
| serious Total, serious adverse events | 27 / 109 |
Outcome results
Primary
Objective Response Rate (RECIST Version 1.1)
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.
Time frame: Up to 12 months
Population: 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).
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Efficacy Analysis Set | Objective Response Rate (RECIST Version 1.1) | Partial Response | 3 Participants |
| Efficacy Analysis Set | Objective Response Rate (RECIST Version 1.1) | Progression | 34 Participants |
| Efficacy Analysis Set | Objective Response Rate (RECIST Version 1.1) | Stable Disease >= 5 Weeks | 46 Participants |
| Efficacy Analysis Set | Objective Response Rate (RECIST Version 1.1) | Not Evaluable | 2 Participants |
| Efficacy Analysis Set | Objective Response Rate (RECIST Version 1.1) | Complete Response | 0 Participants |
| Safety Analysis Set | Objective Response Rate (RECIST Version 1.1) | Not Evaluable | 2 Participants |
| Safety Analysis Set | Objective Response Rate (RECIST Version 1.1) | Complete Response | 0 Participants |
| Safety Analysis Set | Objective Response Rate (RECIST Version 1.1) | Partial Response | 8 Participants |
| Safety Analysis Set | Objective Response Rate (RECIST Version 1.1) | Stable Disease >= 5 Weeks | 59 Participants |
| Safety Analysis Set | Objective Response Rate (RECIST Version 1.1) | Progression | 40 Participants |
Primary
Objective Response Rate (RECIST Version 1.1) Stratified by c-MET Status in Efficacy Analysis Set
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.
Time frame: 12 Months
Population: 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).
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Efficacy Analysis Set | Objective Response Rate (RECIST Version 1.1) Stratified by c-MET Status in Efficacy Analysis Set | Progression | 10 Participants |
| Efficacy Analysis Set | Objective Response Rate (RECIST Version 1.1) Stratified by c-MET Status in Efficacy Analysis Set | Partial Response | 3 Participants |
| Efficacy Analysis Set | Objective Response Rate (RECIST Version 1.1) Stratified by c-MET Status in Efficacy Analysis Set | Not Evaluable | 1 Participants |
| Efficacy Analysis Set | Objective Response Rate (RECIST Version 1.1) Stratified by c-MET Status in Efficacy Analysis Set | Stable Disease >= 5 weeks | 23 Participants |
| Efficacy Analysis Set | Objective Response Rate (RECIST Version 1.1) Stratified by c-MET Status in Efficacy Analysis Set | Complete Response | 0 Participants |
| Safety Analysis Set | Objective Response Rate (RECIST Version 1.1) Stratified by c-MET Status in Efficacy Analysis Set | Stable Disease >= 5 weeks | 19 Participants |
| Safety Analysis Set | Objective Response Rate (RECIST Version 1.1) Stratified by c-MET Status in Efficacy Analysis Set | Progression | 20 Participants |
| Safety Analysis Set | Objective Response Rate (RECIST Version 1.1) Stratified by c-MET Status in Efficacy Analysis Set | Not Evaluable | 1 Participants |
| Safety Analysis Set | Objective Response Rate (RECIST Version 1.1) Stratified by c-MET Status in Efficacy Analysis Set | Partial Response | 0 Participants |
| Safety Analysis Set | Objective Response Rate (RECIST Version 1.1) Stratified by c-MET Status in Efficacy Analysis Set | Complete Response | 0 Participants |
| c-MET Status Unknown [600mg AZD6094 po] | Objective Response Rate (RECIST Version 1.1) Stratified by c-MET Status in Efficacy Analysis Set | Stable Disease >= 5 weeks | 4 Participants |
| c-MET Status Unknown [600mg AZD6094 po] | Objective Response Rate (RECIST Version 1.1) Stratified by c-MET Status in Efficacy Analysis Set | Complete Response | 0 Participants |
| c-MET Status Unknown [600mg AZD6094 po] | Objective Response Rate (RECIST Version 1.1) Stratified by c-MET Status in Efficacy Analysis Set | Partial Response | 0 Participants |
| c-MET Status Unknown [600mg AZD6094 po] | Objective Response Rate (RECIST Version 1.1) Stratified by c-MET Status in Efficacy Analysis Set | Progression | 4 Participants |
| c-MET Status Unknown [600mg AZD6094 po] | Objective Response Rate (RECIST Version 1.1) Stratified by c-MET Status in Efficacy Analysis Set | Not Evaluable | 0 Participants |
| Total [600mg AZD6094 po] | Objective Response Rate (RECIST Version 1.1) Stratified by c-MET Status in Efficacy Analysis Set | Progression | 34 Participants |
| Total [600mg AZD6094 po] | Objective Response Rate (RECIST Version 1.1) Stratified by c-MET Status in Efficacy Analysis Set | Partial Response | 3 Participants |
| Total [600mg AZD6094 po] | Objective Response Rate (RECIST Version 1.1) Stratified by c-MET Status in Efficacy Analysis Set | Complete Response | 0 Participants |
| Total [600mg AZD6094 po] | Objective Response Rate (RECIST Version 1.1) Stratified by c-MET Status in Efficacy Analysis Set | Stable Disease >= 5 weeks | 46 Participants |
| Total [600mg AZD6094 po] | Objective Response Rate (RECIST Version 1.1) Stratified by c-MET Status in Efficacy Analysis Set | Not Evaluable | 2 Participants |
Primary
Objective Response Rate (RECIST Version 1.1) Stratified by c-MET Status in Safety Analysis Set
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.
Time frame: 12 Months
Population: ORR was assessed on the safety analysis set, consisting of all patients who received at least one dose of the study drug (n = 109).
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Efficacy Analysis Set | Objective Response Rate (RECIST Version 1.1) Stratified by c-MET Status in Safety Analysis Set | Progression | 10 Participants |
| Efficacy Analysis Set | Objective Response Rate (RECIST Version 1.1) Stratified by c-MET Status in Safety Analysis Set | Partial Response | 8 Participants |
| Efficacy Analysis Set | Objective Response Rate (RECIST Version 1.1) Stratified by c-MET Status in Safety Analysis Set | Not Evaluable | 1 Participants |
| Efficacy Analysis Set | Objective Response Rate (RECIST Version 1.1) Stratified by c-MET Status in Safety Analysis Set | Stable Disease >= 5 weeks | 27 Participants |
| Efficacy Analysis Set | Objective Response Rate (RECIST Version 1.1) Stratified by c-MET Status in Safety Analysis Set | Complete Response | 0 Participants |
| Safety Analysis Set | Objective Response Rate (RECIST Version 1.1) Stratified by c-MET Status in Safety Analysis Set | Stable Disease >= 5 weeks | 21 Participants |
| Safety Analysis Set | Objective Response Rate (RECIST Version 1.1) Stratified by c-MET Status in Safety Analysis Set | Progression | 25 Participants |
| Safety Analysis Set | Objective Response Rate (RECIST Version 1.1) Stratified by c-MET Status in Safety Analysis Set | Not Evaluable | 1 Participants |
| Safety Analysis Set | Objective Response Rate (RECIST Version 1.1) Stratified by c-MET Status in Safety Analysis Set | Partial Response | 0 Participants |
| Safety Analysis Set | Objective Response Rate (RECIST Version 1.1) Stratified by c-MET Status in Safety Analysis Set | Complete Response | 0 Participants |
| c-MET Status Unknown [600mg AZD6094 po] | Objective Response Rate (RECIST Version 1.1) Stratified by c-MET Status in Safety Analysis Set | Stable Disease >= 5 weeks | 11 Participants |
| c-MET Status Unknown [600mg AZD6094 po] | Objective Response Rate (RECIST Version 1.1) Stratified by c-MET Status in Safety Analysis Set | Complete Response | 0 Participants |
| c-MET Status Unknown [600mg AZD6094 po] | Objective Response Rate (RECIST Version 1.1) Stratified by c-MET Status in Safety Analysis Set | Partial Response | 0 Participants |
| c-MET Status Unknown [600mg AZD6094 po] | Objective Response Rate (RECIST Version 1.1) Stratified by c-MET Status in Safety Analysis Set | Progression | 5 Participants |
| c-MET Status Unknown [600mg AZD6094 po] | Objective Response Rate (RECIST Version 1.1) Stratified by c-MET Status in Safety Analysis Set | Not Evaluable | 0 Participants |
| Total [600mg AZD6094 po] | Objective Response Rate (RECIST Version 1.1) Stratified by c-MET Status in Safety Analysis Set | Progression | 40 Participants |
| Total [600mg AZD6094 po] | Objective Response Rate (RECIST Version 1.1) Stratified by c-MET Status in Safety Analysis Set | Partial Response | 8 Participants |
| Total [600mg AZD6094 po] | Objective Response Rate (RECIST Version 1.1) Stratified by c-MET Status in Safety Analysis Set | Complete Response | 0 Participants |
| Total [600mg AZD6094 po] | Objective Response Rate (RECIST Version 1.1) Stratified by c-MET Status in Safety Analysis Set | Stable Disease >= 5 weeks | 59 Participants |
| Total [600mg AZD6094 po] | Objective Response Rate (RECIST Version 1.1) Stratified by c-MET Status in Safety Analysis Set | Not Evaluable | 2 Participants |
Secondary
Apparent Total Clearance of AZD6094 From Plasma After Single Dose
The number of patients analysed represent the number of patients with evaluable PK parameters for this endpoint.
Time frame: 24 Hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Efficacy Analysis Set | Apparent Total Clearance of AZD6094 From Plasma After Single Dose | 48.4938 L/hour | Standard Deviation 17.3386 |
Secondary
Apparent Volume of Distribution of AZD6094 Following Single Dose
The number of patients analysed represent the number of patients with evaluable PK parameters for this endpoint.
Time frame: 24 Hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Efficacy Analysis Set | Apparent Volume of Distribution of AZD6094 Following Single Dose | 137.4237 Liters | Standard Deviation 36.5971 |
Secondary
Area Under Plasma Concentration Time Curve for AZD6094 After Single Dose
The number of patients analysed represent the number of patients with evaluable PK parameters for this endpoint.
Time frame: 24 Hours
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Efficacy Analysis Set | Area Under Plasma Concentration Time Curve for AZD6094 After Single Dose | 13144.7381 h*ng/mL | Geometric Coefficient of Variation 36.4328 |
Secondary
Area Under Plasma Concentration Time Curve for AZD6094 After Single Dose (Time Zero to Last Measurement)
The number of patients analysed represent the number of patients with evaluable PK parameters for this endpoint.
Time frame: 24 Hours
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Efficacy Analysis Set | 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
Change From Baseline in Target Lesion Tumour Size at 12 Weeks in Efficacy Analysis Set
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.
Time frame: 12 Weeks (at 12 weeks timepoint)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Efficacy Analysis Set | Change From Baseline in Target Lesion Tumour Size at 12 Weeks in Efficacy Analysis Set | -6.3 Percent change | Standard Deviation 21.56 |
| Safety Analysis Set | Change From Baseline in Target Lesion Tumour Size at 12 Weeks in Efficacy Analysis Set | 3.4 Percent change | Standard Deviation 20.05 |
| c-MET Status Unknown [600mg AZD6094 po] | Change From Baseline in Target Lesion Tumour Size at 12 Weeks in Efficacy Analysis Set | 7.1 Percent change | Standard Deviation 0 |
Secondary
Change From Baseline in Target Lesion Tumour Size at 12 Weeks in Safety Analysis Set.
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.
Time frame: 12 Weeks (at 12 week timepoint)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Efficacy Analysis Set | Change From Baseline in Target Lesion Tumour Size at 12 Weeks in Safety Analysis Set. | -10.9 Percent change | Standard Deviation 21.39 |
| Safety Analysis Set | Change From Baseline in Target Lesion Tumour Size at 12 Weeks in Safety Analysis Set. | 4.3 Percent change | Standard Deviation 18.96 |
| c-MET Status Unknown [600mg AZD6094 po] | Change From Baseline in Target Lesion Tumour Size at 12 Weeks in Safety Analysis Set. | 5.1 Percent change | Standard Deviation 17.41 |
Secondary
Duration of Response
Duration 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.
Time frame: Up to 12 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Efficacy Analysis Set | Duration of Response | NA Weeks |
Secondary
Elimination Half-Life of AZD6094 After Single Dose
The number of patients analysed represent the number of patients with evaluable PK parameters for this endpoint.
Time frame: 24 Hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Efficacy Analysis Set | Elimination Half-Life of AZD6094 After Single Dose | 2.0499 Hours | Standard Deviation 0.382 |
Secondary
Mean Residence Time of AZD6094 After Single Dose
The number of patients analysed represent the number of evaluable PK parameters for this endpoint.
Time frame: 24 Hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Efficacy Analysis Set | Mean Residence Time of AZD6094 After Single Dose | 3.9837 Hours | Standard Deviation 0.4813 |
Secondary
Overall Survival Stratified by c-MET Status in the Efficacy Analysis Set
Time frame: Up to 12 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Efficacy Analysis Set | Overall Survival Stratified by c-MET Status in the Efficacy Analysis Set | NA Weeks |
| Safety Analysis Set | Overall Survival Stratified by c-MET Status in the Efficacy Analysis Set | 61.1 Weeks |
| c-MET Status Unknown [600mg AZD6094 po] | Overall Survival Stratified by c-MET Status in the Efficacy Analysis Set | 51.5 Weeks |
Secondary
Overall Survival Stratified by c-MET Status in the Safety Analysis Set
Time frame: Up to 12 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Efficacy Analysis Set | Overall Survival Stratified by c-MET Status in the Safety Analysis Set | NA Weeks |
| Safety Analysis Set | Overall Survival Stratified by c-MET Status in the Safety Analysis Set | 61.1 Weeks |
| c-MET Status Unknown [600mg AZD6094 po] | Overall Survival Stratified by c-MET Status in the Safety Analysis Set | 54.9 Weeks |
Secondary
Peak Plasma Concentration of AZD6094 Following Single Dose
The number of patients analysed represent the number of patients with evaluable PK parameters for this endpoint.
Time frame: 24 Hours
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Efficacy Analysis Set | Peak Plasma Concentration of AZD6094 Following Single Dose | 3038.8984 ng/mL | Geometric Coefficient of Variation 44.4184 |
Secondary
Progression Free Survival Stratified by c-MET Status in the Efficacy Analysis Set
Time frame: Up to 12 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Efficacy Analysis Set | Progression Free Survival Stratified by c-MET Status in the Efficacy Analysis Set | 18.3 Weeks |
| Safety Analysis Set | Progression Free Survival Stratified by c-MET Status in the Efficacy Analysis Set | 9.7 Weeks |
| c-MET Status Unknown [600mg AZD6094 po] | Progression Free Survival Stratified by c-MET Status in the Efficacy Analysis Set | 6.1 Weeks |
Secondary
Progression Free Survival Stratified by c-MET Status in the Safety Analysis Set
Time frame: Up to 12 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Efficacy Analysis Set | Progression Free Survival Stratified by c-MET Status in the Safety Analysis Set | 24.7 Weeks |
| Safety Analysis Set | Progression Free Survival Stratified by c-MET Status in the Safety Analysis Set | 6.6 Weeks |
| c-MET Status Unknown [600mg AZD6094 po] | Progression Free Survival Stratified by c-MET Status in the Safety Analysis Set | 12.1 Weeks |
Secondary
Time to Peak Plasma Concentration of AZD6094 After Single Dose
The number of patients analysed represent the number of patients with evaluable PK parameters for this endpoint.
Time frame: 24 Hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Efficacy Analysis Set | Time to Peak Plasma Concentration of AZD6094 After Single Dose | 2.0 Hours |