CALYPSO
Research type
Research Study
Full title
MEDI4736 combinations in metastatic renal cell carcinoma
IRAS ID
178883
Contact name
Thomas Powles
Contact email
Sponsor organisation
Queen Mary University of London
Eudract number
2015-002042-31
Duration of Study in the UK
3 years, 1 months, 31 days
Research summary
This study is being carried out to see if the drugs MEDI4736, savolitinib and tremelimumab can be used alone or in combination to reduce the size of tumours in patients with kidney cancer.
The drugs being tested in this study have an anti-tumour effect and have been tested in pre-clinical and human studies before. MEDI4736 and tremelimumab work with the immune system to help the body fight against tumour cells with immune cells. Savolitinib works to correct a faulty signal which causes tumour growth.
There are strict inclusion and exclusion criteria for this trial. Broadly speaking, patients with histologically confirmed advanced or metastatic renal cell cancer with a component of either clear cell cancer or papillary cancer are eligible.
If a patient is eligible for the study and decides to take part, they will be enrolled into one of 3 stages of the study.
-First stage: aims to find the optimal dose of MEDI4736+savolitinib.
-Second stage: patients with papillary cell cancer will be treated with MEDI4736+savolitinib. Patients with clear cell cancer will be randomised to one of four treatment arms and receive MEDI4736, savolitinib, MEDI4736+savolitinib, or MEDI4736+tremelimumab.
-Third stage: patients will be tested for biomarkers before enrolment, and depending on the results will be allocated to one of 3 treatments (MEDI4736, savolitinib, or MEDI4736+tremelimumab) to see if certain biomarkers are linked to drug efficacy.All patients will have regular scans, blood tests, and reviews with the clinical team. Patients will be offered optional tumour biopsies. The team will compare the patient’s results from before, during and after treatment in order to see how well the drugs work and if they are safe. Treatment will stop after 12 months, or if the patient’s disease progresses.
Patients will only be involved in one stage of the study.
The study is being carried out in hospitals in England, Scotland, Wales, France and Spain.
Lay summary of study results: What was the purpose of the study?
The purpose of the study was to assess the safety and effectiveness of different treatment combinations for patients with advanced kidney cancer.
In the Renal Cell Carcinoma (RCC) cohort, the study compared:
• Durvalumab alone
• Durvalumab plus tremelimumab
• Durvalumab plus savolitinib
In the PCC cohort, the study investigated:
• Durvalumab plus savolitinib
Durvalumab and tremelimumab are immunotherapy medicines that help the body's immune system recognise and attack cancer cells. Savolitinib is a targeted therapy designed to block a protein called Methyl-nitro-nitrosoguanidine proto-oncogene receptor tyrosine kinase (MET), which may contribute to tumour growth in some kidney cancers.Who took part?
A total of 138 patients with advanced clear cell renal cell carcinoma participated in the Renal Cell Carcinoma (RCC) cohort.
A total of 41 patients with advanced papillary renal cell carcinoma participated in the Papillary Renal Cell Carcinoma (PCC) cohort.
All participants had advanced or metastatic kidney cancer that could not be cured with surgery alone.What were the main findings?
RCC Cohort (Clear Cell Renal Cell Carcinoma)
The study found that the combination of durvalumab and tremelimumab resulted in tumour shrinkage in a greater proportion of patients than durvalumab alone. However, none of the treatment groups achieved the level of benefit that had been pre-defined by the study as necessary to support further development.
The combination treatments did not lead to meaningful improvements in how long patients lived or how long their cancer remained controlled when compared with durvalumab alone.
Side effects were more common in patients receiving combination treatments than in those receiving durvalumab alone.
Overall, the results did not support further development of either durvalumab plus tremelimumab or durvalumab plus savolitinib for patients with previously treated advanced clear cell renal cell carcinoma.PCC Cohort (Papillary Renal Cell Carcinoma)
In the papillary renal cell carcinoma cohort, treatment with durvalumab and savolitinib demonstrated evidence of anti-cancer activity.
Tumour responses were observed in approximately one-third of patients. The greatest benefit was seen in patients whose tumours contained alterations affecting the MET pathway, known as MET-driven tumours.
The treatment combination was generally manageable, and no new safety concerns were identified during the study.
The results suggest that this treatment combination may have potential benefit for some patients with papillary renal cell carcinoma, particularly those with MET-driven disease.What did the study learn?
The CALYPSO study improved understanding of how different treatment approaches perform in specific types of advanced kidney cancer.
For patients with clear cell renal cell carcinoma, the treatments investigated did not demonstrate sufficient benefit to justify further development in this setting.
For patients with papillary renal cell carcinoma, the combination of durvalumab and savolitinib showed encouraging activity, particularly in patients with MET-driven tumours. These findings have informed the design of further clinical research, including larger studies investigating this treatment approach.How will these results be used?
The results from CALYPSO will help researchers and healthcare professionals better understand which treatments may be most effective for different types of kidney cancer.
The findings contribute to ongoing efforts to develop more personalised treatments and improve outcomes for patients with advanced kidney cancer in the future.
The study has now completed and the results have been analysed and reported.REC name
South Central - Hampshire B Research Ethics Committee
REC reference
15/SC/0640
Date of REC Opinion
8 Dec 2015
REC opinion
Further Information Favourable Opinion