Phase I/IIa study to evaluate CCS1477 in advanced tumours v1.0
Research type
Research Study
Full title
An open-label Phase I/IIa study to evaluate the safety and efficacy of CCS1477 as monotherapy and in combination, in patients with advanced solid/metastatic tumours.
IRAS ID
242259
Contact name
Johann de Bono
Contact email
Sponsor organisation
CellCentric Ltd
Eudract number
2018-000285-10
Duration of Study in the UK
3 years, 6 months, 31 days
Research summary
Summary of Research
CCS1477 is a new experimental medication (sponsored by CellCentric Ltd) for a type of prostate cancer called metastatic castration resistant prostate cancer (mCRPC). It is aimed at tumours that are not responsive to, or have become resistant to, existing medications used in late stage disease. CCS1477 may also be used for other cancers with specific gene mutations, again where existing treatments are no longer working. The purpose of this study is to examine the safety, tolerability, pharmacokinetics (PK) and efficacy of CCS1477 when treating patients with mCRPC, when given alone or in combination with other standard mCRPC therapies, and in treating patients with other solid tumour cancers which have a gene mutation in p300 or CBP.It is expected that approximately 150 patients will be recruited from up to 20 hospitals in the UK and US. The study has 5 parts consisting of dose escalation and expansion cohorts. Patients will have regular clinic visits for various safety and clinical benefit assessments, to monitor any side effects and to find out how CCS1477 is handled by the body and affects the tumour.
The information gained in this study will help the sponsor to determine whether CCS1477 is suitable for further studies in humans.
Summary of Results
Thank you to the people who took part The sponsor thanks everyone who took part in this study. The information from this study helps researchers understand whether a medicine called CCS1477 can be used safely and whether it shows early signs of activity against cancer.Who carried out the study?
The study was sponsored by CellCentric. It took place at 19 study centres in the UK, US, and EU.When did the study happen?
The first patient joined the study on 04 July 2018. The last patient completed the study on 23 April 2024.Why was the study needed?
This study looked at a medicine called CCS1477 in people with advanced cancers. The researchers wanted to learn more about its safety, how well patients could tolerate it, how the body processed it, and whether it showed signs of helping to control cancer. CCS1477 was tested both on its own and in combination with other anti-cancer medicines.Who took part?
The study included adults with advanced cancers, including metastatic castration-resistant prostate cancer, metastatic breast cancer, non-small cell lung cancer, and some other advanced solid tumours with certain molecular features that might make them more likely to respond to CCS1477. In total, 310 patients were screened, 235 were assigned to a treatment group, and 219 received at least 1 dose of CCS1477.
What treatments did people receive?
Some people received CCS1477 on its own. Others received CCS1477 with another cancer medicine, such as abiraterone, enzalutamide, darolutamide, or atezolizumab. One planned combination with olaparib was included in the design but was not started.
There was no placebo group and no random assignment to treatment. This means the study cannot prove that CCS1477 works better than another treatment or no treatment.What happened during the study?
Doctors checked people regularly during treatment. These checks included physical examinations, blood tests, heart rhythm tests, scans, and review of medical problems.
The study also measured how much CCS1477 was in the blood. This helped researchers understand how the body handled the medicine.What were the main safety results?
Most patients had at least one side effect during the study. Across the different treatment groups, the most commonly reported side effects included tiredness, anaemia, nausea, reduced appetite, diarrhoea, and in some groups constipation, back pain, or vomiting.
There were 5 side effects that led to death overall, and 1 of these was considered by the investigator to be possibly related to treatment. The study report says there were no new safety concerns or unexpected findings. It also says that, at the recommended dose, tolerability in prostate cancer and solid tumours was good, and that expected side effects were generally considered clinically manageable or reversible through dose interruption.
The study report found no new or unexpected safety concerns with CCS1477. Most side effects were those that researchers expected to see and could usually be managed by adjusting treatment or providing supportive care.
Doctors carefully monitored patients for side effects during the study. The most important side effects to watch for included feeling sick, vomiting, diarrhoea, constipation, stomach pain, changes in blood test results, and low sodium levels.What were the main results on whether CCS1477 may help control cancer?
Researchers looked for early signs that CCS1477 might help control cancer growth. Because this was an early-stage study, it was not designed to prove how well CCS1477 works. However, it did provide some early information about its possible effects.
Some patients showed signs that their cancer responded to treatment. For example, some had a decrease in prostate-specific antigen, or PSA, which is a blood test commonly used to monitor prostate cancer. Others had fewer circulating tumour cells, meaning cancer cells found in the bloodstream. In some patients, scans showed that tumours had shrunk or had stopped growing for a period of time.
The effects of treatment varied between patients, and not everyone benefited from CCS1477.
The study suggested that CCS1477 may have worked better when it was given together with other cancer medicines than when it was given on its own. The most encouraging results were seen in some patients with metastatic castration-resistant prostate cancer, which is prostate cancer that has spread and no longer responds well to treatments that lower male hormones. These patients received CCS1477 with either abiraterone or enzalutamide. In the group receiving CCS1477 with abiraterone, one patient had a reduction of at least 90% in their PSA level compared with the start of treatment.
Some patients with other advanced solid tumours also appeared to benefit. These patients had certain changes in their cancer cells that researchers thought might make them more likely to respond to CCS1477. Six patients had measurable tumour shrinkage, while four others had tumours that stayed the same size and did not grow for a period of time.
Because only a small number of patients were included in each treatment group, it is not possible to draw firm conclusions about how well CCS1477 works.
What did the study show about how CCS1477 behaves in the body?
The study looked at what happens to CCS1477 after people take it, including how much medicine gets into the blood and how long it stays there.
Researchers compared the original version of CCS1477 with a modified version. The modified version led to higher and more consistent levels of CCS1477 in the blood. The highest level in the blood was more than three times higher with the modified version than with the original version, and the body was exposed to more of the medicine overall. The study report concluded that the modified version would be better suited to being taken twice a day.
The study did not show evidence that CCS1477 built up in the body over time when people took repeated doses.
Food also affected CCS1477 levels in the blood. When people took 35 mg of the modified version after a high-fat, high-calorie meal, the medicine reached its highest blood level later, and that highest level was about 30% lower than when CCS1477 was taken without food.
The study also looked at CCS1477 when it was taken with abiraterone, darolutamide, or atezolizumab. These results did not suggest that these medicines had an important effect on each other in the body.
What do these results mean?
The study showed that CCS1477 could generally be given safely, both on its own and together with other cancer medicines. Although side effects were common, they were mostly consistent with what researchers expected and could usually be managed with monitoring or changes to treatment.
The study also found some early signs that CCS1477 may help control cancer in some patients. The most encouraging results were seen when CCS1477 was used together with other treatments, particularly abiraterone or enzalutamide in patients with advanced prostate cancer.
However, this was an early study involving relatively small numbers of patients. This means that the study was designed mainly to learn about safety and dosing rather than to show how well the treatment works. Because this was an early study involving relatively small numbers of patients, it is not possible to draw firm conclusions about the benefits of CCS1477 from this study alone.Are more studies planned?
The information collected during this study has contributed to researchers' understanding of CCS1477 and its effects in patients with advanced cancer. At the time this summary was prepared, no further studies of CCS1477 are currently planned in this type of cancer.Where can I learn more?
If you would like more information about this study, you can contact the study sponsor, CellCentric Limited, who conducted the research: clinical@cellcentric.com.REC name
London - Chelsea Research Ethics Committee
REC reference
18/LO/0543
Date of REC Opinion
27 Apr 2018
REC opinion
Further Information Favourable Opinion