To provide early access (i.e., before marketing authorisation) to tremelimumab 300 mg IV administered once on Day 1 of Cycle 1 plus durvalumab 1500 mg IV followed by durvalumab 1500 mg IV Q4W monotherapy in patients with unresectable HCC.
Overall design This is a multi centre, open-label, early access program (EAP) designed to provide treatment access to intravenous (IV) combination treatment regimen of 300 mg tremelimumab administered IV once on Day 1 of Cycle 1 plus 1500 mg durvalumab IV (MEDI 4736) followed by durvalumab IV monotherapy administered once every 4 weeks (Q4W) for eligible patients with unresectable, hepatocellular carcinoma (HCC). Durvalumab and tremelimumab will be provided free of charge to the patients entering this program. This global EAP will be opened in a staggered fashion, country by country, based on the requesting Treating Physician(s) and local regulations, ending when durvalumab and tremelimumab has received marketing authorisation in first line treatment in patients with unresectable hepatocellular carcinoma. Target patient population Patients with unresectable HCC and Barcelona Clinic Liver Cancer (BCLC) stage B (who are not eligible or no longer suitable for locoregional therapy [LRT]) or stage C before entering the EAP. Program period The EAP will enrol patients and provide resupply of durvalumab and tremelimumab until durvalumab and tremelimumab has received marketing authorisation in first line treatment for patients with unresectable HCC as per local regulations. The EAP will be closed to new patients based on local regulations or when commercially reimbursed product is available. After reimbursement is secured, or denial of reimbursement, or decision by the Sponsor to close the enrolment, whichever occurs first, no new patients can be enrolled after this point. In the event that market license approval or reimbursement should not be granted, contingencies will be made to ensure continued drug supply for patients who are still deriving benefit from durvalumab and tremelimumab. Number of patients: The number of patients who will enrol in the EAP is based on approval of unsolicited requests received from the Treating Physician. Program treatment: On Day 1 of Cycle 1, tremelimumab will be administered first followed by durvalumab 1 hour later. Tremelimumab will be given once on Day 1 of Cycle 1. Durvalumab monotherapy is then given Q4W. Duration of treatment: Patients may continue to receive EAP treatment providing they continue to show clinical benefit, as judged by the Treating Physician, in the absence of unacceptable safety concerns until disease progression, toxicity or withdrawal.
Drug: Durvalumab
Dose: 1500mg Route: IV
Other Name: Imfinzi
Drug: Tremelimumab
Dose: 300mg Route: IV
Inclusion Criteria: 1. Age 18 years and over at the time of screening. 2. Body weight over 30 kg. 3. Confirmed HCC based on histopathological findings from tumour tissues. 4. Must not have received prior systemic therapy for HCC. 5. Must not be eligible for locoregional therapy for resectable HCC. For patients who progressed after locoregional therapy for HCC, locoregional therapy must have been completed at least 28 days before the baseline scan for the programme. 6. Barcelona Clinic Liver Cancer (BCLC) stage B (that is not eligible for locoregional therapy) or stage C (refer to Appendix H). 7. Child-Pugh Score Class A; or Child-Pugh Class B7 or B8 at discretion of treating physician (refer to Appendix I). 8. Patients with HBV infection, characterised by positive hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibodies (anti-HBcAb) with detectable HBV deoxyribonucleic acid (DNA) (≥10 IU/mL or above the limit of detection per local or central lab standard), must be treated with antiviral therapy, as per institutional practice to ensure adequate viral suppression (HBV DNA 90 mmHg or systolic blood pressure >140 mmHg.
15. Any condition interfering with swallowing pills, or other contraindication to oral therapy, or uncontrolled diarrhoea.
16. Active or previously documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [except for diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). Patients without active disease in the last 5 years are excluded unless discussed with the Treating Physician and considered appropriate for EAP participation. The following are exception to this criterion: - Patients with vitiligo or alopecia - Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement - Any chronic skin condition that does not require systemic therapy - Patients with celiac disease controlled by diet alone
17. Patients co-infected with HBV and HCV, or co-infected with HBV and hepatitis D virus (HDV). HBV positive (presence of HbsAg and/or anti-HBcAb with detectable HBV DNA); HCV positive (presence of anti-HCV antibodies); HDV positive (presence of anti-HDV antibodies).
18. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease (ILD), serious chronic GI conditions associated with diarrhoea, inferior vena cava thrombosis, or psychiatric illness/social situations that would limit compliance with EAP requirement, substantially increase the risk of incurring AEs, or compromise the ability of the patient to give written informed consent.
19. History of another primary malignancy except for: - Malignancy treated with curative intent and with known active disease ≥5 years before the first dose of EAP treatment and of low potential risk for recurrence - Patients with a history of prostate cancer of stage
Research Site
Minneapolis, Minnesota, 55404
AstraZeneca Clinical Study Information Center
1-877-240-9479
information.center@astrazeneca.com