Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Carcinoma, Renal Cell

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Papillary Renal Cell Carcinoma

Chromophil Renal Cell Carcinoma

All patients entering the study will take AZD6094 600 mg by mouth (PO) once daily (QD). Treatment will be given continuously.

AZD6094 is a potent and selective small molecule mesenchymal epithelial transition (c-MET) kinase inhibitor.

AZD6094

Henrik-Tobias Arkenau, MD,PhD

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.

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v1.1 There will be a data cut-off after all patients have completed at least 12 weeks of treatment with AZD6094 or withdrawn.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

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

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

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.

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.

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.

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.

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 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.

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

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

SCRI Development Innovations, LLC

AstraZeneca

All patients who received at least one dose of study medication

AZD6094 600 mg Per Day Orally

All participants tested for the presence of c-MET mutations

c-MET Positive [600mg AZD6094 po]

All participants were tested for the presence of c-MET mutations.

c-MET Negative [600mg AZD6094 po]

c-MET Status Unknown [600mg AZD6094 po]

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

ECOG Performance Status (PS): (0) = Fully active; (1) Restricted in physically strenuous activity; (2) Ambulatory and capable of self-care; (3) Capable of limited self-care; (4) Completely disabled

ECOG Performance Status

PRCC Confirmation from Central Laboratory

Stage Classification

Renal Cell Classification

Risk categories for patients were obtained from the Memorial Sloan Kettering Cancer Center (MSKCC) risk category prognostic model in advanced renal cell cancer, as follows: Favourable risk = 0 risk factors; Intermediate risk = 10 or 2 risk factors; Poor risk = 3 or more risk factors. Risk factors include: Karnofsky performance status \< 80%; time from diagnosis to salvage treatment \< 1 year; haemoglobin \< lower limit of normal (LLN); corrected serum calcium \> ULN; and serum lactate dehydrogenase \> 1.5 x ULN.

MSKCC Risk Group

Weight

All subjects who received at least one dose of AZD6094 are included in the baseline analysis.

For the secondary outcome measure Duration of Response the median was not calculable because at data cut-off some participants were still responding.

Point to note: All patients on this trial received 600mg AZD6094 po.

Senior Medical Director, Savolitinib

All patients with measurable disease, PRCC confirmed by central laboratory and received at least 1 dose of study medication

Efficacy Analysis Set

All patients who have received at least 1 dose of study medication

Safety Analysis Set

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).

Objective Response Rate (RECIST Version 1.1)

Total [600mg AZD6094 po]

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).

Objective Response Rate (RECIST Version 1.1) Stratified by c-MET Status in Efficacy Analysis Set

ORR was assessed on the safety analysis set, consisting of all patients who received at least one dose of the study drug (n = 109).

Objective Response Rate (RECIST Version 1.1) Stratified by c-MET Status in Safety Analysis Set

Progression Free Survival Stratified by c-MET Status in the Efficacy Analysis Set

Overall Survival Stratified by c-MET Status in the Efficacy Analysis Set

Progression Free Survival Stratified by c-MET Status in the Safety Analysis Set

Overall Survival Stratified by c-MET Status in the Safety Analysis Set

Change From Baseline in Target Lesion Tumour Size at 12 Weeks in Efficacy Analysis Set

Change From Baseline in Target Lesion Tumour Size at 12 Weeks in Safety Analysis Set.

Safety Analysis Set [600mg AZD6094 po]

Duration of Response

All patients that received at least one dose of study medication and had evaluable PK data

Pharmacokinetic Analysis Set [600mg AZD6094 po]

Peak Plasma Concentration of AZD6094 Following Single Dose

Time to Peak Plasma Concentration of AZD6094 After Single Dose

Apparent Volume of Distribution of AZD6094 Following Single Dose

Area Under Plasma Concentration Time Curve for AZD6094 After Single Dose

Area Under Plasma Concentration Time Curve for AZD6094 After Single Dose (Time Zero to Last Measurement)

Apparent Total Clearance of AZD6094 From Plasma After Single Dose

Mean Residence Time of AZD6094 After Single Dose

Elimination Half-Life of AZD6094 After Single Dose

Overall Study

Antineoplastic Agents

All Drugs and Chemicals

Sunitinib

Angiogenesis Inhibitors

Growth Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

600 mg (400 mg if \<50 kg) by mouth (PO) with a meal once daily (QD), continuously

Savolitinib

50 mg by mouth (PO) once daily (QD), with or w/o food, 4 weeks on/2weeks off

Toni K Choueiri, MD

This study is designed for patients diagnosed with MET-driven, unresectable and locally advanced or metastatic Papillary Renal Cell Carcinoma. The purpose of this study is to see if an investigational new anti-cancer medication, savolitinib, is effective in treating patients with MET-driven PRCC, how it compares with another medication frequently used to treat this disease called sunitinib, and what side effects it might cause.

Savolitinib vs. Sunitinib in MET-driven PRCC.

A Phase III, Open Label, Randomised, Controlled, Multi-Centre Study To Assess the Efficacy and Safety of Savolitinib Versus Sunitinib in Patients With MET-Driven, Unresectable and Locally Advanced, Or Metastatic Papillary Renal Cell Carcinoma (PRCC)

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Progressive Disease (PD): \>= 20% increase in the sum of diameters of TLs and an absolute increase in sum of diameters of \>=5mm (compared to the previous minimum sum) or progression of NTLs or a new lesion. PFS is the time from date of randomisation until the date of PD (defined by Recist 1.1 and confirmed by BICR) or death (by any cause in the absence of progression) regardless of whether the patient withdrew from randomised therapy or received another anti-cancer therapy prior to progression.

Time between the date of randomisation and the date of death due to any cause.

Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Complete Response (CR): Disappearance of all target and non-target lesions and no new lesions; Partial Response (PR): \>= 30% decrease in the sum of diameters of Target Lesions (compared to baseline) and no new lesions. ORR is the percentage of patients with at least 1 visit response of CR or PR prior to progression or any further therapy.

Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Complete Response (CR): Disappearance of all target and non-target lesions and no new lesions; Partial Response (PR): \>= 30% decrease in the sum of diameters of Target Lesions (compared to baseline) and no new lesions. DoR is the time from the date of first documented response until the date of documented progression or death in the absence of disease progression.

Disease control rate at 6 months is defined as the percentage of patients who have a best objective response of Complete Response or Partial Response in that period or who have demonstrated Stable Disease for a minimum interval of 23 weeks.

Disease control rate at 12 months is defined as the percentage of patients who have a best objective response of complete responses or partial responses in that period or who have demonstrated stable disease for a minimum interval of 47 weeks.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Phase II Trial to Evaluate the Efficacy of AZD6094 (HMPL-504) in Patients With Papillary Renal Cell Carcinoma (PRCC)	NCT02127710	Papillary Renal...	AZD6094	18 Years - 99 Years	AstraZeneca
Savolitinib vs. Sunitinib in MET-driven PRCC.	NCT03091192	Carcinoma Carcinoma, Rena... Kidney Neoplasm... Urologic Neopla... Kidney Diseases Neoplasms by Si... Enzyme Inhibito... Protein Kinase ...	Savolitinib Sunitinib	18 Years - 130 Years	AstraZeneca

Spots Global Cancer Trial Database for papillary renal cell cancer