A phase II trial of CY-101 in participants with adrenocortical cancer
| ISRCTN | ISRCTN15479264 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN15479264 |
| Integrated Research Application System (IRAS) | 1012105 |
| Protocol serial number | CRUKD/25/001 |
| Sponsor | Cancer Research UK |
| Funder | Cancer Research UK |
- Submission date
- 08/11/2025
- Registration date
- 03/02/2026
- Last edited
- 03/02/2026
- Recruitment status
- Not yet recruiting
- Overall study status
- Ongoing
- Condition category
- Cancer
Plain English summary of protocol
Background and study aims
In this clinical trial, researchers are testing a drug called CY-101. CY-101 is a type of drug called a peptide. CY-101 works in 2 ways: 1) It binds to cancer cells and destroys their outer layer (membrane), leading to the killing of the cells; 2) It enters into the cancer cells and activates a protein called Axin2, which in turn reduces the levels of another protein that helps cancer cells to survive, called β-catenin. Both these ways of working trigger the body’s immune system to kill more cancer cells, both in the treated tumour and tumours that have spread elsewhere in the body.
CY-101 has been tested in clinical trials before and now researchers want to find out if it will be effective in treating people with adrenocortical carcinoma (ACC) that has spread to nearby tissues or to other organs. The main aims of the trial are to: find out the best dose of CY-101 that can be given safely to people with ACC; find out whether CY-101 is effective in treating people with ACC; learn more about the potential side effects of CY-101; learn about how CY-101 might affect the quality of life of people with ACC; and learn more about what happens to CY-101 inside the body.
Who can participate?
The trial aims to recruit 41 participants aged 16 years and over with ACC who have received at least 1 but no more than 2 previous lines of treatment for their cancer.
What does the study involve?
This clinical trial has 2 phases (Phase 2A and Phase 2B). In Phase 2A (dose optimisation), 2 different doses of CY-101 will be tested to decide which is the best dose to give to a larger number of participants with ACC in Phase 2B. Phase 2B (dose expansion) of the trial will help us gather more information on whether CY-101 is effective in treating people with ACC, CY-101’s effects on the body and what happens to CY-101 as it moves through the body.
Due to the small size and type of molecule that CY-101 is, the only way to give the drug and get it close to cancer cells is to inject it directly into the tumour lesions (an area where cancer is present); this is called an intratumoural injection. In most cases, this will be under the guidance of an ultrasound or computed tomography (CT) scan.
What are the possible benefits and risks of participating?
Although the anticipated benefit for people with ACC participating in this trial is unknown at this stage, they will be contributing to the further understanding of how best to treat ACC, which may benefit patients in the future.
CY-101 is a new drug that has been tested in a small number of people. While some side effects are known, others may still be discovered. Participants will be closely monitored throughout the trial. Possible risks relevant to this trial include: reactions or pain at the place where the study drug is injected; allergic reactions; bleeding (haemorrhage); effects related to activation of the body’s immune system; digestive problems such as nausea, vomiting or diarrhoea; changes in blood tests and liver function; and risks related to reproduction (i.e. relating to pregnancy and embryo development). Due to these risks, participants on the trial will be monitored closely to find out the effects of CY-101, and the trial has been carefully designed to keep participants safe. Participants will also be required to follow the trial contraceptive requirements and/or not be pregnant to ensure their unborn child is not exposed to any risks.
Other risks and burdens a participant may encounter are: radiation exposure from CT and positron emission tomography scans; discomfort or bruising from blood tests and biopsies; and the inconvenience of visiting the hospital for regular tests and visits.
Where is the study run from?
Cancer Research UK
When is the study starting and how long is it expected to run for?
March 2026 to July 2032
Who is funding the study?
Cancer Research UK
Who is the main contact?
Dr Debashis Sarker, drugdev@cancer.org.uk
Contact information
Scientific
Centre for Drug Development, 2 Redman Place
London
E20 1JQ
United Kingdom
| Phone | +44 (0)300 123 1022 |
|---|---|
| drugdev@cancer.org.uk |
Public
Centre for Drug Development, 2 Redman Place
London
E20 1JQ
United Kingdom
| Phone | +44 (0)300 123 1022 |
|---|---|
| drugdev@cancer.org.uk |
Principal investigator
3rd Floor, Bermondsey Wing, St Thomas Street
London
SE1 9RT
United Kingdom
| Phone | +44 (0)207 1884249 |
|---|---|
| debashis.sarker@kcl.ac.uk |
Study information
| Primary study design | Interventional | |
|---|---|---|
| Allocation | N/A: single arm study | |
| Masking | Open (masking not used) | |
| Control | Uncontrolled | |
| Assignment | Single | |
| Purpose | Treatment | |
| Scientific title | A Cancer Research UK phase II trial of CY-101 given via intratumoural administration in locally advanced or metastatic adrenocortical carcinoma (CLARITY) | |
| Study acronym | CLARITY | |
| Study objectives | Main objectives of the trial: 1.To find the best dose of CY-101 to be injected into the tumours of people who have adrenocortical carcinoma (ACC) that has spread into nearby areas or to other organs. 2.To investigate whether CY-101 can shrink the tumours of people who have ACC that has spread into nearby areas or to other organs, when CY-101 is injected into their tumours. Secondary objectives of the trial: 1.To learn more about the side-effects of CY-101 when it is injected into the tumours of people who have ACC that has spread into nearby areas or to other organs. 2.To learn more about whether, and for how long, CY-101 can shrink tumours when it is injected into the tumours of people who have ACC that has spread into nearby areas or to other organs. 3.To learn about how CY-101 might affect the quality of life of people who have ACC that has spread into nearby areas or to other organs, when CY-101 is injected into their tumours. 4.To find out more about the pharmacokinetics (PK) of CY-101, i.e., what happens to the drug in the body over time, when it is injected into the tumours of people who have ACC that has spread into nearby areas or other organs. | |
| Ethics approval(s) |
Approved 05/01/2026, London – Westminster (2 Redman Place, Stratford, London, E20 1JQ, United Kingdom; 0207 104 8169; westminster.rec@hra.nhs.uk), ref: 25/LO/0815 | |
| Health condition(s) or problem(s) studied | Adrenocortical carcinoma | |
| Intervention | This clinical trial has 2 phases (Phase 2A and Phase 2B). It is a Phase II multi-centre open-label randomized dose-optimisation and single-arm dose expansion trial design In Phase 2A, a total of 16 evaluable participants (i.e. people for whom the main aims of the trial can be assessed) will be recruited and randomised in a 1:1 ratio (i.e. in equal numbers) into 2 cohorts of 8 participants each to compare 20 mg and 40 mg dose levels of CY-101 given via IT injection at a volume of 4 mL once every 2 weeks (Q2W) in cycles consisting of 14 days. Participants will be randomised using an electronic data capture system. In Phase 2B, participants will be treated at the chosen best dose level from Phase 2A. CY-101 will be administered via IT injection at a volume of 4 mL Q2W in cycles consisting of 14 days. Phase 2B will include 33 evaluable participants, which may include eligible participants from Phase 2A who received the selected dose and are evaluable for whether their ACC responded to CY-101. In total, the trial requires 41 evaluable participants across both phases to complete the trial. Participants may receive CY-101 for up to 52 weeks (maximum of 26 cycles) unless there are unacceptable side effects, there is evidence that their cancer is progressing, or the Investigator decides it is in the participant’s best interests to be withdrawn. Participants may be allowed to continue for a further 26 weeks or 13 cycles (whichever is shorter) if they are found to be benefiting from CY-101; however, this depends on whether there are enough supplies of CY-101. It is expected that after this, CY-101 will be permanently discontinued. If a participant is withdrawn from the trial, the trial doctor will discuss further treatment options with the participant and will arrange for their care to continue outside of the clinical trial. Participants will be followed up for safety for 28 days after their last dose of CY-101 and for survival for at least 12 months after their last dose. | |
| Intervention type | Drug | |
| Phase | Phase II | |
| Drug / device / biological / vaccine name(s) | CY-101 | |
| Primary outcome measure(s) |
Phase IIa: Determining an optimal dose of CY-101 based upon review of all clinically relevant data including but not limited to toxicity, efficacy, quality of life data and PK parameters at the end of Phase IIa and EoT | |
| Key secondary outcome measure(s) |
Phase 2a and 2b | |
| Completion date | 31/07/2032 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Mixed |
| Lower age limit | 16 Years |
| Upper age limit | 99 Years |
| Sex | All |
| Target sample size at registration | 41 |
| Key inclusion criteria | 1. Written (signed and dated) informed consent and be capable of co-operating with CY-101 administration and follow-up. 2. Histologically confirmed ACC that is either locally advanced and not amenable to surgical resection or metastatic, with evidence of disease progression post the most recent line of therapy. 3. Participants must have received treatment with at least 1 line, but not more than 2 prior lines, of systemic therapy for established locally advanced or metastatic disease, and must have received mitotane therapy within these lines of therapy for advanced/metastatic disease (or as neoadjuvant/adjuvant therapy). Participants must have relapsed within 1 year of neoadjuvant/adjuvant therapy for this to be considered a line of treatment. 4. At least 1 lesion that is objectively evaluable or measurable, according to itRECIST. Previously irradiated lesions cannot be counted as target lesions unless they have clearly progressed after radiotherapy. Participants also require at least 1 separate lesion(s) amenable for IT injection by a clinician or interventional radiologist under ultrasound-assisted guidance. Refer to protocol for further details. 5. Adequate tissue available for biomarker testing, from either archival tissue or pre-treatment biopsy. 6. Life expectancy of ≥12 weeks. 7. Eastern Cooperative Oncology Group performance status of 0-2. 8. Haematological and biochemical indices within the prescribed ranges. 9. Aged 16 years or over at the time consent is given. |
| Key exclusion criteria | 1. Radiotherapy (except for palliative reasons), endocrine therapy, chemotherapy or other Investigational Medicinal Products (IMPs) during the previous 28 days before the first dose of CY-101. Continued treatment with mitotane during the trial to control hormonal symptoms is permitted under certain conditions as specified in the trial protocol. Mitotane plasma level monitoring is to be maintained and documented during the trial. 2. Prior treatment with a Wnt inhibitor. 3. Ongoing toxic manifestations of previous treatments greater than Common Terminology Criteria for Adverse Events Grade 1 (other than alopecia of any grade or Grade 2 peripheral neuropathy). Exceptions apply. 4. Any central nervous system metastases (unless patients had local therapy and are asymptomatic, radiologically stable for 4 weeks and off steroids for the last 4 weeks). 5. Women who are pregnant or breastfeeding (or planning to breastfeed). 6. Women of childbearing potential. However, those patients who are not already pregnant or breastfeeding (or planning to breastfeed) are eligible, provided they have a negative highly sensitive serum pregnancy test ≤7 days before trial entry and agree to follow the trial’s contraceptive requirements. 7. Male patients with partners of childbearing potential. However, those patients who agree to follow the trial’s contraceptive requirements are eligible. 8. Major surgery from which the patient has not yet recovered. 9. At high medical risk because of non-malignant systemic disease, including active uncontrolled infection. 10. Serologically positive for hepatitis B virus or hepatitis C virus (HCV). Patients with previous HCV exposure but no current infection are eligible. 11. Known untreated human immunodeficiency virus (HIV) infection. Patients on established antiretroviral medication and who have well-controlled HIV infection/disease are eligible, provided they meet protocol-specified criteria. 12. Allergy or hypersensitivity to any of the ingredients/excipients in the CY-101 formulation. 13. Significant cardiovascular disease. As defined in the trial protocol. 14. Extensive radiotherapy to >25% of bone marrow within 12 weeks prior to the first dose of CY-101. 15. Participating in or plans to participate in another interventional clinical trial whilst taking part in this trial of CY-101. See protocol for more information. 16. Current malignancies of other types, with certain exceptions as per the trial protocol. Cancer survivors who have undergone potentially curative therapy for a prior malignancy, have no evidence of that disease for ≥5 years and are deemed at negligible risk for recurrence are eligible for the trial. 17. Any congenital immunodeficiency syndrome. 18. Active autoimmune disease that has required systemic treatment in the 2 years before trial entry. 19. Use of systemic corticosteroids (apart from replacement doses for endocrinopathy up to an equivalent of 10 mg QD prednisolone or 20 mg QD prednisolone if receiving mitotane concurrently). 20. Prior adverse reaction to cancer immunotherapy that required intravenous steroid treatment or other immunosuppressive treatment. 21. Live, attenuated vaccine within 28 days before the first dose of CY-101. 22. Evidence of bleeding diathesis, or anticoagulant or antiplatelet therapy (excluding prophylactic low molecular weight heparin or low-dose aspirin). 23. High burden of metastatic disease defined as ≥4 organs involved with metastases or greater than 12 individual metastases, including primary tumour. 24. Patients with uncontrolled hormonal secretion (according to the judgement of the Investigator), e.g. Cushing's or mineralocorticoid excess causing uncontrolled hypertension, diabetes, and hypokalaemia. 25. Any other condition that, in the Investigator’s opinion, would mean that the trial is not in the best interests of the patient. |
| Date of first enrolment | 01/03/2026 |
| Date of final enrolment | 31/01/2030 |
Locations
Countries of recruitment
- United Kingdom
- England
Study participating centres
London
SE1 9RT
England
Clatterbridge Road
Bebington
Wirral
CH63 4JY
England
Beckett Street
Leeds
LS9 7TF
England
London
SW3 6JJ
England
Du Cane Road
London
W12 0HS
England
Withington
Manchester
M20 4BX
England
Mindelsohn Way
Edgbaston
Birmingham
B15 2GW
England
Results and Publications
| Individual participant data (IPD) Intention to share | Yes |
|---|---|
| IPD sharing plan summary | Available on request |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request |
Editorial Notes
06/01/2026: ISRCTN received notification of combined HRA/MHRA approval for this trial on 06/01/2026.
10/11/2025: Study's existence confirmed by Health Research Authority (HRA) (UK).
