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Contact the study team using the details below to take part. If there are no contact details below please ask your doctor in the first instance.
Advanced liver cancer
This information is provided directly by researchers, and we recognise that it isn't always easy to understand. We are working with researchers to improve the accessibility of this information. In some summaries, you may come across links to external websites. These websites will have more information to help you better understand the study.
Liver cancer is increasingly common and there are currently few drug treatments that are proven to be effective in patients with advanced disease. There is some evidence that drugs that target a molecule known as PDL-1, such as durvalumab, can enable the immune system to eradicate cancer cells and have some activity in shrinking liver cancer, but are not sufficient on their own to improve survival in patients with advanced disease. Experiments in the laboratory suggest that targeting immune cells known as chemokines with a drug called AZD5069 can increase the effects of anti-PDL-1 antibody therapy on liver cancer. The aim of this study is to find the recommended dose of AZD5069 when given in combination with durvalumab in patients with liver cancer and determine if this treatment is effective at shrinking liver cancers.
Start dates may differ between countries and research sites. The research team are responsible for keeping the information up-to-date.
The recruitment start and end dates are as follows:
You can take part if:
Current inclusion criteria as of 08/04/2025:
1. Histologically or cytologically confirmed hepatocellular carcinoma that is not suitable for surgery (with or without transplantation) or locoregional therapies
2. Patients with evidence of background liver disease or without evidence of underlying liver disease will be eligible
3. Patients who have either (a) not received prior systemic anti-cancer therapy; or (b) who have progressed on, or who are intolerant to, no more than one line or prior therapy with either sorafenib or lenvatinib (patients who change 1st-line tyrosine kinase therapy from sorafenib to lenvatinib, and vice versa, within 2 months of starting treatment because of toxicity, and without evidence of disease progression, will be considered as having had one line of therapy), or an anti-PD(L)-1 antibody either as monotherapy or in combination with bevacizumab, a CTLA-4 antibody, or lenvatinib. Patients who developed > grade 2 immune-mediated toxicity, or who discontinued treatment due to immune-mediated toxicity, or who progressed within the first 12 weeks of previous immunotherapy treatment will be excluded. However, patients who developed immune-mediated endocrinopathy that has resolved and are on hormone replacement therapy are eligible.
Patients who have received pre-operative (neo-adjuvant) systemic therapy followed by surgery with curative intent, with no macroscopic or microscopic residual disease, and in whom recurrent disease occurs >12 months after surgical resection, will be considered to be treatment-naĂŻve for unresectable HCC
4. Able to undergo a pre-treatment and on-treatment biopsy of a liver tumour and of non-tumour liver for pharmacodynamic and predictive biomarker studies
5. ECOG performance status ≤1 (Appendix II)
6. Age ≥18 years
7. Measurable disease by RECIST 1.1. Patients who have previously been treated with TACE or ablation will be eligible provided there is either a new measurable lesion (that has not been treated with ablation/TACE) or a new, reproducibly measurable, hyper-vascular area with washout within a previously treated lesion or area
8. Estimated life expectancy greater than 3 months
9. Adequate haematological function as defined by:
9.1. Haemoglobin (Hb) ≥90 g/l
9.2. Neutrophil Count ≥1.5 x 109 /l
9.3. Platelets ≥75 x 10e9 /l
10. Child–Pugh Score A (≤6) [Appendix VIII]
11. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <3.0 x ULN
12. Bilirubin <34 umol/l
13. Adequate renal function with creatinine clearance / glomerular filtration rate >50 ml/min as calculated by local standard practice
14. Ability to swallow oral medication
15. Written informed consent prior to performing any study-related procedures
16. Patients with past or ongoing HCV infection will be eligible for the study. Patients who have been treated for HCV infection must have completed their treatment at least 1 month prior to starting trial therapy
17. Patients with controlled hepatitis B will be eligible as long as they meet the following criteria:
17.1. Antiviral therapy for HBV must be given for at least 4 weeks and HBV viral load must be less than 500 IU/ml prior to the first dose of the study drug. Patients on active HBV therapy with viral loads under 500 IU/ml should stay on the same therapy throughout the study treatment.
17.2. Patients who are positive for anti-hepatitis B core antibody HBc, negative for hepatitis B surface antigen (HBsAg), and negative or positive for anti-hepatitis B surface antibody (HBs), and who have an HBV vi
You may not be able to take part if:
Current exclusion criteria as of 08/04/2025:1. Pregnant or breastfeeding women2. Women of childbearing potential* and men with female partners of childbearing potential who are not willing to use two forms of contraception, including one highly effective method. Men with pregnant or breastfeeding partners should be advised to use barrier method contraception to prevent exposure to the foetus or neonate during treatment.*A woman is considered of childbearing potential (WOCBP) i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause.3. Cardiovascular disease defined as Stage II to IV congestive heart failure (CHF) as determined by the New York Heart Association (NYHA) classification system, or history of myocardial infarction (MI), or cardiac arrhythmia associated with haemodynamic instability, or unstable angina, or cerebral vascular accident, or transient ischemia, if any have occurred within the previous 12 months prior to study treatment.4. Any other serious medical or psychiatric disorder that would be, in the opinion of the investigator, a contraindication to either the trial procedures or to therapy with AZD5069 or durvalumab5. Patients with a lack of physical integrity of the GI tract leading to a malabsorption syndrome or intestinal obstruction that would impair the administration and absorption of oral therapy6. Any previous > grade 2 toxicity or discontinuation of therapy due to immune-mediated toxicity with an immune checkpoint inhibitor. Patients who developed immune-mediated endocrinopathy that has resolved and are on hormone replacement therapy will be considered eligible.7. Major surgery within 14 days of starting study treatment and patients must have recovered from any effects of major surgery8. Patients with a known hypersensitivity to AZD5069 or durvalumab or any of the excipients of the products9. Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion:9.1. Intranasal, inhaled, or topical steroids; or local steroid injections (e.g., intra-articular injection)9.2. Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisolone or equivalent9.3. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication) and chemotherapy-induced nausea and vomiting10. History of allogenic organ transplant11. Active autoimmune disorders, or prior documented severe autoimmune or inflammatory disorders requiring immunosuppressive treatment (including inflammatory bowel disease [e.g., colitis, Crohn’s disease], diverticulitis with the exception of diverticulosis, coeliac disease, irritable bowel syndrome, or other serious gastrointestinal chronic conditions associated with diarrhoea); systemic lupus erythematosus; Wegener syndrome (granulomatosis with polyangiitis), Graves’ disease; rheumatoid arthritis, hypophysitis, uveitis, etc. The following are exceptions to this criterion:11.1. Patients with vitiligo or alopecia11.2. Diabetes mellitus type I or resolved childhood asthma/atopy11.3. Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement11.4. Any chronic skin condition that does not require systemic therapy11.5. Patients with coeliac disease controlled by diet alone12. Receipt of any investigational anticancer therapy within 28 days or 5 half-lives, whichever is longer, prior to the first dose of study treatment.13. Concurrent enrolment in another clinical study unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.14. Receipt of the last dose of an approved (marketed) anticancer therapy (chemotherapy, targeted therapy, biologic therapy, monoclonal antibodies etc) or radiotherapy within 28 days prior to the first dose of study treatment15. Other malignancy within 5 years except for non-invasive malignancies such as cervical carcinoma in situ, non-melanoma carcinoma of the skin, prostate cancer or ductal carcinoma in situ of the breast that has/have been surgically cured16. Mean QT interval corrected for heart rate using Fridericia’s formula (QTcF) ≥470 mscalculated from three ECG reports (within 5 minutes at least 1 minute apart).17. History of active primary immunodeficiency18. History of (non-infectious) interstitial lung disease or pneumonitis that required steroids or current pneumonitis.19. Patients with an active infection requiring systemic therapy.20. Receipt of live attenuated vaccine within 30 days prior to the first dose of study therapy. Note: patients, if enrolled, should not receive a live attenuated vaccine during the study and up to 30 days after the last dose of any investigational products (IPs).21. Current or prior use of the following concomitant medication within 14 days before the first dose of AZD5069: Strong or moderate inducers or inhibitors of CYP3A4; CYP2C9 substrates with a narrow therapeutic index (e.g. warfarin and coumarin derivatives); Pgp substrates with a narrow therapeutic index (e.g. digoxin, dabigatran); sensitive CYP2B6 substrates; BCRP substrates that reduce blood neutrophils or herbal supplements (see https://drug-interactions.medicine.iu.edu/MainTable.aspx).22. Patients who weigh ≤30 kg will be excluded
Previous exclusion criteria:1. Pregnant or breastfeeding women2. Women of childbearing potential* and men with female partners of childbearing potential who are not willing to use two forms of contraception, including one highly effective method. Men with pregnant or breastfeeding partners should be advised to use barrier method contraception to prevent exposure to the foetus or neonate during treatment. *A woman is considered of childbearing potential (WOCBP) i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. 3. Cardiovascular disease defined as Stage II to IV congestive heart failure (CHF) as determined by the New York Heart Association (NYHA) classification system, or history of myocardial infarction (MI), or cardiac arrhythmia associated with haemodynamic instability, or unstable angina, or cerebral vascular accident, or transient ischemia, if any have occurred within the previous 12 months prior to study treatment.4. Any other serious medical or psychiatric disorder that would be, in the opinion of the investigator, a contraindication to either the trial procedures or to therapy with AZD5069 or durvalumab5. Patients with a lack of physical integrity of the GI tract leading to a malabsorption syndrome or intestinal obstruction that would impair the administration and absorption of oral therapy6. Any previous > grade 2 toxicity or discontinuation of therapy due to immune-mediated toxicity with an immune checkpoint inhibitor7. Major surgery within 14 days of starting study treatment and patients must have recovered from any effects of major surgery8. Patients with a known hypersensitivity to AZD5069 or durvalumab or any of the excipients of the products9. Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion:9.1. Intranasal, inhaled, or topical steroids; or local steroid injections (e.g., intra-articular injection)9.2. Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisolone or equivalent9.3. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication) and chemotherapy-induced nausea and vomiting10. History of allogenic organ transplant11. Active autoimmune disorders, or prior documented severe autoimmune or inflammatory disorders requiring immunosuppressive treatment (including inflammatory bowel disease [e.g., colitis, Crohn’s disease], diverticulitis with the exception of diverticulosis, coeliac disease, irritable bowel syndrome, or other serious gastrointestinal chronic conditions associated with diarrhoea); systemic lupus erythematosus; Wegener syndrome (granulomatosis with polyangiitis), Graves’ disease; rheumatoid arthritis, hypophysitis, uveitis, etc. The following are exceptions to this criterion:11.1. Patients with vitiligo or alopecia11.2. Diabetes mellitus type I or resolved childhood asthma/atopy11.3. Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement11.4. Any chronic skin condition that does not require systemic therapy11.5. Patients with coeliac disease controlled by diet alone12. Receipt of any investigational anticancer therapy within 28 days or 5 half-lives, whichever is longer, prior to the first dose of study treatment.13. Concurrent enrolment in another clinical study unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.14. Receipt of the last dose of an approved (marketed) anticancer therapy (chemotherapy, targeted therapy, biologic therapy, monoclonal antibodies etc) or radiotherapy within 28 days prior to the first dose of study treatment15. Other malignancy within 5 years except for non-invasive malignancies such as cervical carcinoma in situ, non-melanoma carcinoma of the skin, prostate cancer or ductal carcinoma in situ of the breast that has/have been surgically cured16. Mean QT interval corrected for heart rate using Fridericia’s formula (QTcF) ≥470 mscalculated from three ECG reports (within 5 minutes at least 1 minute apart).17. History of active primary immunodeficiency18. History of (non-infectious) interstitial lung disease or pneumonitis that required steroids or current pneumonitis.19. Patients with an active infection requiring systemic therapy.20. Receipt of live attenuated vaccine within 30 days prior to the first dose of study therapy. Note: patients, if enrolled, should not receive a live attenuated vaccine during the study and up to 30 days after the last dose of any investigational products (IPs).21. Current or prior use of the following concomitant medication within 14 days before the first dose of AZD5069: Strong or moderate inducers or inhibitors of CYP3A4; CYP2C9 substrates with a narrow therapeutic index (e.g. warfarin and coumarin derivatives); Pgp substrates with a narrow therapeutic index (e.g. digoxin, dabigatran); sensitive CYP2B6 substrates; BCRP substrates that reduce blood neutrophils or herbal supplements (see https://drug-interactions.medicine.iu.edu/MainTable.aspx).22. Patients who weigh ≤30 kg will be excluded
Below are the locations for where you can take part in the trial. Please note that not all sites may be open.
Prof
Jeffry
Evans
+44 (0)1413017073
j.evans@crukscotlandinstitute.ac.uk
The study is sponsored by NHS Greater Glasgow and Clyde; University of Glasgow and funded by Cancer Research UK.
Your feedback is important to us. It will help us improve the quality of the study information on this site. Please answer both questions.
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