Clinical Trial Results:
MEDI4736 combinations in metastatic renal cell carcinoma
|
Summary
|
|
EudraCT number |
2015-002042-31 |
Trial protocol |
ES |
Global end of trial date |
17 Jul 2024
|
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
29 Aug 2025
|
First version publication date |
29 Aug 2025
|
Other versions |
|
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
010580QM
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
Queen Mary University of London
|
||
Sponsor organisation address |
Mile End Road, London, United Kingdom, E1 2EF
|
||
Public contact |
Mays Jawad, Queen Mary University of London, +44 2078827260, sponsorsrep@bartshealth.nhs.uk
|
||
Scientific contact |
Mays Jawad, Queen Mary University of London, +44 2078827260, sponsorsrep@bartshealth.nhs.uk
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
17 Jul 2024
|
||
Is this the analysis of the primary completion data? |
Yes
|
||
Primary completion date |
17 Jul 2024
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
17 Jul 2024
|
||
Was the trial ended prematurely? |
No
|
||
|
General information about the trial
|
|||
Main objective of the trial |
De-escalation phase: To determine the recommended dose of MEDI4736 and savolitinib in combination by assessment of dose limiting toxicities.
Expansion phase: To determine how well different combinations of MEDI4736, savolitinib and tremelimumab can reduce tumour sizes in patients with papillary and clear cell renal cell carcinoma.
|
||
Protection of trial subjects |
Eligibility criteria for this study were selected to enhance patient safety. A number of exclusion criteria were based on the known safety profiles of the study drug treatments. All enrolled patients were evaluated clinically before and throughout their participation in the study. Safety evaluations consisted of medical interviews, adverse event recording, and laboratory assessments. Patients were monitored for adverse events (all grades), serious adverse events, and any toxicities requiring treatment interruption or discontinuation during the course of the study. Outcomes of pre-specified early safety reviews that affected study conduct were communicated promptly to Investigators for onward reporting to the appropriate ethics committees.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
05 May 2016
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
Yes
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Spain: 96
|
||
Country: Number of subjects enrolled |
United Kingdom: 83
|
||
Worldwide total number of subjects |
179
|
||
EEA total number of subjects |
96
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
123
|
||
From 65 to 84 years |
55
|
||
85 years and over |
1
|
||
|
||||||||||||||||
|
Recruitment
|
||||||||||||||||
Recruitment details |
The study opened to recruitment on 05 May 2016 with Phase Ib recruiting 7 patients in total. Phase IIa opened to recruitment on 05 January 2017, with total recruitment of 181 patients (RCC/sRCC: 138; PCC 41). The PCC cohort closed in July 2018, and the RCC/sRCC cohort closed in March 2021 after also meeting its target. | |||||||||||||||
|
Pre-assignment
|
||||||||||||||||
Screening details |
7 patients were recruited from a single site as part of phase 1b to assess recomended DLT. 179 patients were enrolled into phase II. | |||||||||||||||
|
Pre-assignment period milestones
|
||||||||||||||||
Number of subjects started |
179 | |||||||||||||||
Number of subjects completed |
179 | |||||||||||||||
|
Period 1
|
||||||||||||||||
Period 1 title |
Phase II (overall period)
|
|||||||||||||||
Is this the baseline period? |
Yes | |||||||||||||||
Allocation method |
Randomised - controlled
|
|||||||||||||||
Blinding used |
Not blinded | |||||||||||||||
|
Arms
|
||||||||||||||||
Are arms mutually exclusive |
Yes
|
|||||||||||||||
|
Arm title
|
Savolitinib and Durvalumab | |||||||||||||||
Arm description |
Savolitinib (600mg OD) and Durvalumab (1500mg Q4W) | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Savolitinib
|
|||||||||||||||
Investigational medicinal product code |
||||||||||||||||
Other name |
||||||||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||
Dosage and administration details |
Patients self-administered a 200 mg dose of savolitinib tablets by mouth daily.
|
|||||||||||||||
Investigational medicinal product name |
Durvalumab
|
|||||||||||||||
Investigational medicinal product code |
||||||||||||||||
Other name |
MEDI4736
|
|||||||||||||||
Pharmaceutical forms |
Solution for infusion
|
|||||||||||||||
Routes of administration |
Infusion
|
|||||||||||||||
Dosage and administration details |
500mg vial solution for infusion after dilution. A starting dose of 1500mg (for patients >30kg in weight) was administered every 4 weeks using an IV bag containing 0.9% (w/v) saline or 5% (w/v) dextrose, with a final MEDI4736 concentration ranging from 1 to 15 mg/mL, and delivered through an IV administration set with a 0.2- or 0.22-μm in-line filter.
|
|||||||||||||||
|
Arm title
|
Savolitinib alone | |||||||||||||||
Arm description |
savolitinib (600mg OD) only | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Savolitinib
|
|||||||||||||||
Investigational medicinal product code |
||||||||||||||||
Other name |
||||||||||||||||
Pharmaceutical forms |
Tablet
|
|||||||||||||||
Routes of administration |
Oral use
|
|||||||||||||||
Dosage and administration details |
600mg once daily. Self administered daily.
|
|||||||||||||||
|
Arm title
|
Durvalumab alone | |||||||||||||||
Arm description |
MEDI4736 alone (1500mg Q4W) | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Durvalumab
|
|||||||||||||||
Investigational medicinal product code |
||||||||||||||||
Other name |
MEDI4736
|
|||||||||||||||
Pharmaceutical forms |
Solution for infusion
|
|||||||||||||||
Routes of administration |
Infusion
|
|||||||||||||||
Dosage and administration details |
500mg vial solution for infusion after dilution. A starting dose of 1500mg (for patients >30kg in weight) was administered every 4 weeks using an IV bag containing 0.9% (w/v) saline or 5% (w/v) dextrose, with a final MEDI4736 concentration ranging from 1 to 15 mg/mL, and delivered through an IV administration set with a 0.2- or 0.22-μm in-line filter.
|
|||||||||||||||
|
Arm title
|
Tremelimumab plus Durvalumab | |||||||||||||||
Arm description |
Tremelimumab (75mg Q4W) plus Durvalumab (1500mg Q4W for 4 cycles), followed by Durvulumab alone (1500mg Q4W) | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Durvalumab
|
|||||||||||||||
Investigational medicinal product code |
||||||||||||||||
Other name |
MEDI4736
|
|||||||||||||||
Pharmaceutical forms |
Solution for infusion
|
|||||||||||||||
Routes of administration |
Infusion
|
|||||||||||||||
Dosage and administration details |
500mg vial solution for infusion after dilution. A starting dose of 1500mg (for patients >30kg in weight) was administered every 4 weeks using an IV bag containing 0.9% (w/v) saline or 5% (w/v) dextrose, with a final MEDI4736 concentration ranging from 1 to 15 mg/mL, and delivered through an IV administration set with a 0.2- or 0.22-μm in-line filter.
|
|||||||||||||||
Investigational medicinal product name |
Tremelimumab
|
|||||||||||||||
Investigational medicinal product code |
||||||||||||||||
Other name |
||||||||||||||||
Pharmaceutical forms |
Solution for infusion
|
|||||||||||||||
Routes of administration |
Infusion
|
|||||||||||||||
Dosage and administration details |
400mg vial solution for infusion after dilution. A dose of 75mg (for patients >30kg in weight) was administered using an IV bag containing 0.9% (w/v) saline or 5% (w/v) dextrose, with a final tremelimumab concentration ranging from 0.10 to 10mg/mL.
|
|||||||||||||||
|
||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Savolitinib and Durvalumab
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Savolitinib (600mg OD) and Durvalumab (1500mg Q4W) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Savolitinib alone
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
savolitinib (600mg OD) only | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Durvalumab alone
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
MEDI4736 alone (1500mg Q4W) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Tremelimumab plus Durvalumab
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Tremelimumab (75mg Q4W) plus Durvalumab (1500mg Q4W for 4 cycles), followed by Durvulumab alone (1500mg Q4W) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Subject analysis sets
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set title |
Clear cell cohort
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Renal Cell Cohort
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set title |
Papillary Cell Cohort
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set type |
Per protocol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Papillary Cell Cohort
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
Savolitinib and Durvalumab
|
||
Reporting group description |
Savolitinib (600mg OD) and Durvalumab (1500mg Q4W) | ||
Reporting group title |
Savolitinib alone
|
||
Reporting group description |
savolitinib (600mg OD) only | ||
Reporting group title |
Durvalumab alone
|
||
Reporting group description |
MEDI4736 alone (1500mg Q4W) | ||
Reporting group title |
Tremelimumab plus Durvalumab
|
||
Reporting group description |
Tremelimumab (75mg Q4W) plus Durvalumab (1500mg Q4W for 4 cycles), followed by Durvulumab alone (1500mg Q4W) | ||
Subject analysis set title |
Clear cell cohort
|
||
Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Renal Cell Cohort
|
||
Subject analysis set title |
Papillary Cell Cohort
|
||
Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Papillary Cell Cohort
|
||
|
||||||||||||||||||||||
End point title |
Objective Response Rate | |||||||||||||||||||||
End point description |
||||||||||||||||||||||
End point type |
Primary
|
|||||||||||||||||||||
End point timeframe |
ORR based on measurements (Response Evaluation Criteria in Solid Tumours version 1.1 [RECIST v1.1]) taken at baseline, week 4 and every 8 weeks until disease progression.
|
|||||||||||||||||||||
|
||||||||||||||||||||||
Statistical analysis title |
Objective Response Rate | |||||||||||||||||||||
Comparison groups |
Savolitinib and Durvalumab v Savolitinib alone v Durvalumab alone v Tremelimumab plus Durvalumab v Clear cell cohort v Papillary Cell Cohort
|
|||||||||||||||||||||
Number of subjects included in analysis |
358
|
|||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||
Analysis type |
other | |||||||||||||||||||||
Method |
||||||||||||||||||||||
Parameter type |
Not applicable - response rate only | |||||||||||||||||||||
Point estimate |
0
|
|||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||
level |
95% | |||||||||||||||||||||
sides |
1-sided
|
|||||||||||||||||||||
lower limit |
0 | |||||||||||||||||||||
upper limit |
- | |||||||||||||||||||||
|
|||||||||||||||||||||||||||||
End point title |
Progression Free Survival | ||||||||||||||||||||||||||||
End point description |
|||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||
End point timeframe |
PFS defined as the time from the date of enrolment/randomisation to the date of first documented disease progression (RECIST v1.1) or death from any cause, whichever occurs first.
|
||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||
Statistical analysis title |
Progression Free Survival | ||||||||||||||||||||||||||||
Comparison groups |
Savolitinib and Durvalumab v Savolitinib alone v Durvalumab alone v Tremelimumab plus Durvalumab v Papillary Cell Cohort v Clear cell cohort
|
||||||||||||||||||||||||||||
Number of subjects included in analysis |
317
|
||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||
Analysis type |
other [1] | ||||||||||||||||||||||||||||
P-value |
= 0.999 [2] | ||||||||||||||||||||||||||||
Method |
Kaplan-Meier median PFS (no formal compa | ||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||
| Notes [1] - Kaplan-Meier medians and 95% CIs were calculated. No hypothesis testing was performed. [2] - Median progression-free survival (PFS) was estimated using the Kaplan-Meier method. No formal hypothesis testing (e.g., log-rank test or Cox regression) was performed for this secondary endpoint. The above parameter entry is provided solely to meet s |
|||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||
End point title |
Overall Survival | ||||||||||||||||||||||||||||
End point description |
|||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||
End point timeframe |
OS defined as the time from enrolment/randomisation to death from any cause. All deaths will be included, whether they occur on study or following treatment discontinuation. For patients who have not died, OS overall survival will be censored at the dat
|
||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||
Statistical analysis title |
Survival analysis (Kaplan-Meier) | ||||||||||||||||||||||||||||
Statistical analysis description |
Kaplan-Meier method used to estimate OS distribution
|
||||||||||||||||||||||||||||
Comparison groups |
Savolitinib and Durvalumab v Savolitinib alone v Durvalumab alone v Tremelimumab plus Durvalumab v Clear cell cohort v Papillary Cell Cohort
|
||||||||||||||||||||||||||||
Number of subjects included in analysis |
317
|
||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||
Analysis type |
other | ||||||||||||||||||||||||||||
P-value |
= 999 [3] | ||||||||||||||||||||||||||||
Method |
Hypothesis testing not performed | ||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||
| Notes [3] - Median PFS and 95% CI estimated using Kaplan-Meier method. No formal hypothesis test was performed; no p-value calculated. |
|||||||||||||||||||||||||||||
|
||||||||||||||||||||||
End point title |
Duration of Response | |||||||||||||||||||||
End point description |
||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
Duration of response defined as the time from first documentation of confirmed CR or PR to disease progression (RECIST v1.1) or death from any cause, whichever occurs first.
|
|||||||||||||||||||||
|
||||||||||||||||||||||
| Notes [4] - No response seen |
||||||||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
All AEs will be collected throughout the study as described in the schedule of assessments, from the time the patient gives informed consent to the safety follow-up visit or PD visit, whichever occurs at a later date.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
Safety reporting is reported for the entire clear cell cohort and papillary cohort. The following was collected: AE term, date of onset, date of resolution, CTCAE grade, seriousness, causality.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
CTCAE | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
4.03
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Papillary Cohort
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Papillary Cohort | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Clear Cell Cohort
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
08 Mar 2016 |
Summary of changes: protocol updates of: section 6.11 (maximum tolerated dose), section 8.2 (population of analysis to reflect change for maximum tolerated dose), section 6.18 (Contraception advice updated to reflect HMA guidance), section 6.12.1 (Dosing modifications and toxicity management guidelines for Immune Mediated Reactions associated with durvalumab and Tremelimumab) and Section 12 of Patient information sheets to reflect updated safety information re durvalumab. |
||
16 Nov 2016 |
Summary of changes: updated protocol and patient information sheets: durvalumab dose changes in all parts of the study, removing a treatment arm from the phase IIa (randomisation/dose expansion), Clinical biochemistry monitoring for potential endocrinopathy, Vital sign monitoring during and after durvalumab and tremelimumab Infusions, PK blood collection and research blood collection, Toxicity guidelines, Statistical considerations. Updates to IMP label templates and updates to IBs, specifically durvalumab IB has been updated to Edition 9 dated 22 Jan 2016 and Tremelimumab IB has been updated to Edition 6 (11th feb 2016) and edition 7 (7th Jun 2016). |
||
07 Dec 2016 |
Summary of changes: amendment of protocol section 6.12.2 and patient information sheet to include ‘Stevens-Johnson Syndrome’ as an AE. |
||
03 Mar 2017 |
Summary of changes: addition of 1 UK site |
||
10 Mar 2017 |
Summary of changes: addition of 2 UK sites (University Hospital Bristol and Mid Essex Hospital) and change of PI at Western General Hospital |
||
24 Apr 2017 |
Summary of changes: amendment of protocol section 6.12.2 and patient information sheet section 12 to include pyrexia as an AE. |
||
20 Jul 2018 |
Summary of changes: addition of 1 UK site |
||
24 Aug 2018 |
Summary of changes: protocol and patient information sheet updated to include triplicate ECGs weekly during cycle 1 and at each cycle thereafter as an urgent safety measure for potential Savolitinib-induced QTc prolongation. |
||
22 Feb 2019 |
Summary of changes: change of PI at one UK site |
||
07 Mar 2019 |
Summary of changes: Addition of QMUL Malta as the Legal Representative within the EU in the event the United Kingdom becomes classed as a third country. |
||
20 Mar 2019 |
Summary of changes: Change of savolitinib formulation from uncoated to film-coated. Addition of Weil am Rhein Fisher facility in Germany as contingency in case of a no-deal Brexit. |
||
23 Aug 2019 |
Summary of changes: removal of savolitinib alone arm; submission of updated IBs for MEDI4736, Savolitinib and Tremelimumab. Submission of new Letter of Access for MEDI4736 and Tremelilmumab IMPDs. Updated: GP Letter V2.0, PIS V10.0 for PCC and RCC Cohort and Protocol V7.0. Change of sponsor representative and study statistician. General protocol administrative updates and changes to align with new IBs. |
||
05 Nov 2019 |
Summary of changes: change of PI at UK site |
||
16 Jun 2020 |
Summary of changes: Submission of updated investigator brochures for MEDI4736 (V15.0 08-Oct-2019), Savolitinib (V6.1 28-Oct-2019) and Tremelimumab (V10.0 08-Oct-2019). |
||
03 Aug 2020 |
Summary of changes: Update to IMP labelling: Specifically, update to the MEDI4736 outer box and MEDI4736 vial label to reference that the IMP is a solution for intravenous use. The MEDI4736 outer carton and MEDI4736 vial label has also been updated to state that the protocol should be referenced for directions of use. |
||
24 Nov 2021 |
Summary of changes: Savolitinib – updated UK letter of access was submitted in parallel with AstraZeneca submitting an updated Savolitinib IMPD.
|
||
17 May 2022 |
Summary of changes: Updates to IBs including the Reference Safety Information (RSI) for Durvalumab (MEDI4736) and Savolitinib, updated text for the IRAS form and the PIS following Re-review of radiation exposure by HRA Radiation Assurance to ensure these documents accurately reflect the protocol’s schedule of assessments and participants’ expected radiation exposure. |
||
07 Sep 2023 |
Summary of Changes: Updates to IB’s for for Durvalumab (MEDI4736) and Savolitinib. There are no updates to the RSI in the Savolitinib IB V9.0, and the changes in the Durvalumab (MEDI4736) IB V18.0 RSI are related to system organ class updates. PIS has also been changed to include new events and study end date has been extended from July 2023 to July 2024. |
||
21 Dec 2023 |
Summary of changes: This amendment is related to discontinuation of research blood sample collection. -This was originally sent to be submitted to MHRA on 10/0ct/2023 but was missed in error and was finally sent on 31/0ct/2023 when the error was discovered |
||
23 May 2024 |
Summary of changes: This amendment is related to the changes to the end of trial definition, changing it from last patient last visit, which included 2 years post treatment survival follow up to last patient last treatment visit alongside updates to all three study IMP IB’s. Savolitinib IB V10.2, Tremelimumab V11.0 and Durvalumab (MEDI4736) v19.0 |
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| As part of substantial amendment 13, the savolitinib only arm was removed. This was due to changes in the treatment landscape that meant monotherapy should not be explored further. | |||
Online references |
|||
| http://www.ncbi.nlm.nih.gov/pubmed/36809050 |
|||
