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NCT02127710

A Phase II Trial to Evaluate the Efficacy of AZD6094 (HMPL-504) in Patients With Papillary Renal Cell Carcinoma (PRCC)

Completed Phase 2 Results posted Last updated 19 April 2021
What this trial tests

Phase 2 trial testing AZD6094 in Papillary Renal Cell Cancer in 111 participants. Completed in 20 April 2020.

Timeline
30 April 2014
Primary endpoint
14 April 2016
20 April 2020

Quick facts

Lead sponsorAstraZeneca
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment111
Start date30 April 2014
Primary completion14 April 2016
Estimated completion20 April 2020
Sites23 locations across United Kingdom, Canada, United States, Spain

Drugs / interventions tested

Conditions studied

Sponsor

AstraZeneca — full company profile →

Who can join

Adults 18 to 99, any sex, with Papillary Renal Cell Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Objective Response Rate (RECIST Version 1.1) Primary · 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.

GroupValue95% CI
Efficacy Analysis Set0
Safety Analysis Set0
Efficacy Analysis Set3
Safety Analysis Set8
Efficacy Analysis Set46
Safety Analysis Set59
Efficacy Analysis Set34
Safety Analysis Set40
Objective Response Rate (RECIST Version 1.1) Stratified by c-MET Status in Efficacy Analysis Set Primary · 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.

GroupValue95% CI
c-MET Positive [600mg AZD6094 po]0
c-MET Negative [600mg AZD6094 po]0
c-MET Status Unknown [600mg AZD6094 po]0
Total [600mg AZD6094 po]0
c-MET Positive [600mg AZD6094 po]3
c-MET Negative [600mg AZD6094 po]0
c-MET Status Unknown [600mg AZD6094 po]0
Total [600mg AZD6094 po]3
c-MET Positive [600mg AZD6094 po]23
c-MET Negative [600mg AZD6094 po]19
c-MET Status Unknown [600mg AZD6094 po]4
Total [600mg AZD6094 po]46
c-MET Positive [600mg AZD6094 po]10
c-MET Negative [600mg AZD6094 po]20
c-MET Status Unknown [600mg AZD6094 po]4
Total [600mg AZD6094 po]34
Objective Response Rate (RECIST Version 1.1) Stratified by c-MET Status in Safety Analysis Set Primary · 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.

GroupValue95% CI
c-MET Positive [600mg AZD6094 po]0
c-MET Negative [600mg AZD6094 po]0
c-MET Status Unknown [600mg AZD6094 po]0
Total [600mg AZD6094 po]0
c-MET Positive [600mg AZD6094 po]8
c-MET Negative [600mg AZD6094 po]0
c-MET Status Unknown [600mg AZD6094 po]0
Total [600mg AZD6094 po]8
c-MET Positive [600mg AZD6094 po]27
c-MET Negative [600mg AZD6094 po]21
c-MET Status Unknown [600mg AZD6094 po]11
Total [600mg AZD6094 po]59
c-MET Positive [600mg AZD6094 po]10
c-MET Negative [600mg AZD6094 po]25
c-MET Status Unknown [600mg AZD6094 po]5
Total [600mg AZD6094 po]40
Progression Free Survival Stratified by c-MET Status in the Efficacy Analysis Set Secondary · Up to 12 months
GroupValue95% CI
c-MET Positive [600mg AZD6094 po]18.312.3 – 35.4
c-MET Negative [600mg AZD6094 po]9.76.1 – 12.4
c-MET Status Unknown [600mg AZD6094 po]6.15.1 – NA
Overall Survival Stratified by c-MET Status in the Efficacy Analysis Set Secondary · Up to 12 months
GroupValue95% CI
c-MET Positive [600mg AZD6094 po]NA34.6 – NA
c-MET Negative [600mg AZD6094 po]61.129.4 – NA
c-MET Status Unknown [600mg AZD6094 po]51.58.1 – NA
Progression Free Survival Stratified by c-MET Status in the Safety Analysis Set Secondary · Up to 12 months
GroupValue95% CI
c-MET Positive [600mg AZD6094 po]24.717.7 – 35.4
c-MET Negative [600mg AZD6094 po]6.66.1 – 11.9
c-MET Status Unknown [600mg AZD6094 po]12.16.1 – 41.9
Overall Survival Stratified by c-MET Status in the Safety Analysis Set Secondary · Up to 12 months
GroupValue95% CI
c-MET Positive [600mg AZD6094 po]NA42.9 – NA
c-MET Negative [600mg AZD6094 po]61.140.6 – 106.7
c-MET Status Unknown [600mg AZD6094 po]54.918.4 – NA
Change From Baseline in Target Lesion Tumour Size at 12 Weeks in Efficacy Analysis Set Secondary · 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.

GroupValue95% CI
c-MET Positive [600mg AZD6094 po]-6.3± 21.56
c-MET Negative [600mg AZD6094 po]3.4± 20.05
c-MET Status Unknown [600mg AZD6094 po]7.1± 0
Change From Baseline in Target Lesion Tumour Size at 12 Weeks in Safety Analysis Set. Secondary · 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.

GroupValue95% CI
c-MET Positive [600mg AZD6094 po]-10.9± 21.39
c-MET Negative [600mg AZD6094 po]4.3± 18.96
c-MET Status Unknown [600mg AZD6094 po]5.1± 17.41
Duration of Response Secondary · 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.

GroupValue95% CI
Safety Analysis Set [600mg AZD6094 po]NA18.1 – NA
Peak Plasma Concentration of AZD6094 Following Single Dose Secondary · 24 Hours

The number of patients analysed represent the number of patients with evaluable PK parameters for this endpoint.

GroupValue95% CI
Pharmacokinetic Analysis Set [600mg AZD6094 po]3038.8984± 44.4184
Time to Peak Plasma Concentration of AZD6094 After Single Dose Secondary · 24 Hours

The number of patients analysed represent the number of patients with evaluable PK parameters for this endpoint.

GroupValue95% CI
Pharmacokinetic Analysis Set [600mg AZD6094 po]2.00.5 – 8.0

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 12 months. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

AZD6094 600 mg Per Day Orally
Serious: 27/109 (25%)
Deaths: 57/109

Serious adverse events (36 terms)

ReactionSystemAZD6094 600 mg Per Day Ora…
Acute kidney injuryRenal and urinary disorders
AnaemiaBlood and lymphatic system disorders
AscitesGastrointestinal disorders
ConstipationGastrointestinal disorders
Abdominal incarcerated herniaGastrointestinal disorders
Abdominal painGastrointestinal disorders
Adrenal insufficiencyEndocrine disorders
CellulitisInfections and infestations
CholecystitisHepatobiliary disorders
DehydrationMetabolism and nutrition disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Hepatic encephalopathyNervous system disorders
HyperkalemiaMetabolism and nutrition disorders
HyponatraemiaMetabolism and nutrition disorders
Lung InfectionInfections and infestations
NauseaGastrointestinal disorders
PainGeneral disorders
PericarditisCardiac disorders
Pleural effusionRespiratory, thoracic and mediastinal disorders
PneumoniaInfections and infestations
PneumonitisRespiratory, thoracic and mediastinal disorders
SepsisInfections and infestations
Transaminases increasedInvestigations
Urinary tract infectionInfections and infestations
VomitingGastrointestinal disorders
Other adverse events (52 terms — click to expand)

ReactionSystemAZD6094 600 mg Per Day Ora…
NauseaGastrointestinal disorders
FatigueGeneral disorders
Peripheral oedemaGeneral disorders
VomitingGastrointestinal disorders
ConstipationGastrointestinal disorders
Decreased appetiteMetabolism and nutrition disorders
DiarrhoeaGastrointestinal disorders
Blood creatinine increasedInvestigations
AnaemiaBlood and lymphatic system disorders
Back painMusculoskeletal and connective tissue disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
CoughRespiratory, thoracic and mediastinal disorders
Aspartate aminotransferase increasedInvestigations
Weight decreasedInvestigations
HypoalbuminaemiaMetabolism and nutrition disorders
ArthalgiaMusculoskeletal and connective tissue disorders
Alanine aminotransferase increasedInvestigations
Pain in extremityMusculoskeletal and connective tissue disorders
DizzinessNervous system disorders
ProteinuriaRenal and urinary disorders
Dyspnoea exertionalRespiratory, thoracic and mediastinal disorders
Musculoskeletal painMusculoskeletal and connective tissue disorders
Abdominal painGastrointestinal disorders
Musculoskeletal chest painMusculoskeletal and connective tissue disorders
Flank painMusculoskeletal and connective tissue disorders
DysgeusiaNervous system disorders
AstheniaGeneral disorders
OedemaGeneral disorders
Weight increasedInvestigations
HyperglycaemiaMetabolism and nutrition disorders
HyponatremiaMetabolism and nutrition disorders
HeadacheNervous system disorders
Chest painGeneral disorders
Blood alklaine phosphatase increasedInvestigations
HyperkalaemiaMetabolism and nutrition disorders
Muscle spasmMusculoskeletal and connective tissue disorders
Abdominal distensionGastrointestinal disorders
StomatitisGastrointestinal disorders
Mucosal inflammationGeneral disorders
HypomagnesaemiaMetabolism and nutrition disorders

Most-reported serious reactions: Acute kidney injury, Anaemia, Ascites, Constipation, Abdominal incarcerated hernia, Abdominal pain, Adrenal insufficiency, Cellulitis.

Data from ClinicalTrials.gov NCT02127710 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Targeting <i>MET</i> Dysregulation in Cancer.
    Recondo G, Che J, Jänne PA, Awad MM. · · 2020 · cited 174× · PMID 32532746 · DOI 10.1158/2159-8290.cd-19-1446
  2. c-Met as a Target for Personalized Therapy.
    Garajová I, Giovannetti E, Biasco G, Peters GJ. · · 2015 · cited 106× · PMID 26628860 · DOI 10.4137/tog.s30534
  3. Medical treatment of renal cancer: new horizons.
    Greef B, Eisen T. · · 2016 · cited 76× · PMID 27490806 · DOI 10.1038/bjc.2016.230
  4. MET-Targeted Therapies and Clinical Outcomes: A Systematic Literature Review.
    Dong Y, Xu J, Sun B, Wang J, et al · · 2022 · cited 50× · PMID 35266116 · DOI 10.1007/s40291-021-00568-w
  5. Characterizing the outcomes of metastatic papillary renal cell carcinoma.
    Connor Wells J, Donskov F, Fraccon AP, Pasini F, et al · · 2017 · cited 37× · PMID 28414866 · DOI 10.1002/cam4.1048
  6. The Molecular Characteristics of Non-Clear Cell Renal Cell Carcinoma: What's the Story Morning Glory?
    Marchetti A, Rosellini M, Mollica V, Rizzo A, et al · · 2021 · cited 21× · PMID 34207825 · DOI 10.3390/ijms22126237
  7. First-line therapy for adults with advanced renal cell carcinoma: a systematic review and network meta-analysis.
    Aldin A, Besiroglu B, Adams A, Monsef I, et al · · 2023 · cited 20× · PMID 37146227 · DOI 10.1002/14651858.cd013798.pub2
  8. Unveiling the Role of HGF/c-Met Signaling in Non-Small Cell Lung Cancer Tumor Microenvironment.
    Yao S, Liu X, Feng Y, Li Y, et al · · 2024 · cited 16× · PMID 39201787 · DOI 10.3390/ijms25169101

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