A study of AZD5363 for advanced cancer

The study team found that capivasertib was safe to have. And they decided on the best dose and treatment plan. 

They also looked at how well it worked for people with breast cancer and women’s cancers with the PIK3CA or AKT1 gene change. But they found that on its own, capivasertib didn’t shrink the cancer as much as researchers had hoped.

So the study was expanded to look at whether it worked better in combination with a hormone therapy. The hormone therapy they used is called fulvestrant. Everyone who had this combination of treatment had:

• breast cancer that was oestrogen receptor positive
• the AKT1 or PTEN gene change

About this study
To begin with there were 4 parts to this study testing capivasertib on its own.  Parts A to D. 

Parts E and F of the study were added to look at the combination of capivasertib with fulvestrant. Parts E and F weren’t open in the UK.

Part A and B were for people with any solid tumour. 

Part C and D were for people with:

•  cancer of the ovary, cervix or womb or
• breast cancer that was ER positive or HER2 positive or
• tumours in other parts of the body

Part E and F were for women with breast cancer that was ER positive .

In summary:

• Part A looked at the best dose to have (dose escalation) 
• Part B learnt more about how the drug worked (dose expansion)
• Part C looked at capivasertib in people with PIK3CA in their cancer cells
• Part D looked at capivasertib in people with the AKT1 gene change in their cancer cells
• Part E looked at capivasertib and fulvestrant in people with the AKT1 gene change in their cancer cells
• Part F looked at capivasertib and fulvestrant in people with the PTEN gene change in their cancer cells

Results for Part A and part B
90 people joined this part. A few people had a low dose of capivasertib. If they didn’t have bad side effects the next few people had a higher dose. And so on, until they found the best dose to give. 

There were 3 different treatment schedules. 

• 47 people had capivasertib everyday (continuous treatment). 
• 21 people had capivasertib for 4 days followed by 3 days off treatment each week.
• 22 people had capivasertib for 2 days followed by 5 days off treatment each week.

The best dose in each schedule was:

• 320mg in people having continuous treatment
• 480mg in people having treatment 4 days on and 3 days off each week 
• 640mg in people having treatment 2 days on and 5 days off each week

Researchers then looked at the best dose and schedule overall. To do this they looked at blood samples, tumour samples, and side effects. They found this was 480mg twice a day for 4 days followed by 3 days off treatment. 

Everyone in Part C and Part D had this dose. In Part E and Part F they had a slightly lower dose. 

Researchers also thought the 640mg might be useful in combination studies in the future. 

Results for Part C
59 women joined this part. They all had a change in the PIK3CA gene in the cancer cells. 

• 31 had breast cancer.
• 28 had women’s cancer.

Researchers looked at how well treatment worked. To do this they looked at tumour samples. They had samples for 54 people. 

Throughout any study, the researchers check whether treatment is working or not. In this part of the study they looked at whose cancer got smaller. But they found treatment hadn’t worked as well as they had hoped. It didn’t shrink the tumour in enough people to show that it was helping. So they stopped this part of the study early.  

Results for Part D
59 people joined Part D. They all had a change in the AKT1 gene in the cancer cells. 

• 20 had breast cancer that was ER positive .
• 19 had women’s cancer.
• 20 had other types of cancer.

The team looked at how well treatment worked.

They confirmed the cancer got a bit smaller in:

• 4 people who had breast cancer
• 3 people who had women’s cancer
• 1 person who had another type of cancer

The team say it worked best in people with breast and womb cancer that was ER positive. 

Results for Part E 
44 people with breast cancer joined Part E. They all had a change in the AKT1 gene in the cancer cells. 

Everyone had capivasertib and fulvestrant. Researchers looked at how well this combination of treatment worked. They found the cancer got a bit smaller in:

• just under 4 out of 10 people (36%) whose fulvestrant had stopped working in the past
• about 2 out of 10 people (20%) who hadn’t had fulvestrant in the past 

The team found that capivasertib and fulvestrant worked for some people. This included those who had fulvestrant in the past. 

They also found that most of the side effects of this combination were manageable. Some of the common bad side effects included:

• diarrhoea
• high blood pressure
• skin rash

Results for Part F
31 women with breast cancer women joined this part. They all had a change in the PTEN gene in the cancer cells. 

Everyone had capivasertib and fulvestrant. 

The researchers looked at how well treatment worked. They looked at whose cancer got smaller. This happened in 5 people. 

The team also found that the side effects were manageable. The team concluded that capivasertib and fulvestrant worked for a few people. This included people whose cancer got worse on fulvestrant.

Side effects
The most common side effects of capivasertib were:

• diarrhoea
• feeling sick
• tiredness
• skin rash

A more serious side effect included high levels of sugar in the blood.

Conclusion
The study team found the best dose and treatment plan for capivasertib. But they found that as a treatment on its own, it didn’t work to shrink the cancer enough. 

Researchers are now are looking at this drug in combination with several other drugs. For example, alongside:

• chemotherapy or chemotherapy and an immunotherapy  for breast cancer
• hormone therapy  for breast cancer
• hormone therapy drugs called abiraterone or enzalutamide for prostate cancer

All trial results help doctors and researchers understand more about different cancers and the best way to treat them.

Where this information comes from    

We have based this summary on information from the research team. Some information they sent us has been reviewed by independent specialists (peer reviewed ) and published in a medical journal. And some may not have been. The figures we quote above were provided by the trial team who did the research. We have not analysed the data ourselves.