TheraSphere With and Without Durvalumab and Tremelimumab for HCC (ROWAN)

• ClinicalTrials.gov Identifier: NCT05063565
• Recruitment Status: Suspended
• First Posted: October 1, 2021
• Last Update Posted: March 20, 2023
• Sponsor: Boston Scientific Corporation
• Collaborator: Biocompatibles UK Ltd
• Information provided by (Responsible Party): Boston Scientific Corporation

Study Description

Brief Summary:

The objective of the ROWAN clinical study is to assess the durability of local tumor control in HCC patients who receive TheraSphere followed by durvalumab and tremelimumab, compared to those who receive TheraSphere treatment alone.

Condition or disease	Intervention/treatment	Phase
Hepatocellular Carcinoma	Device: TheraSphere Y-90 glass microsphere therapy; Drug: Durvalumab (Imfinzi) immunotherapy; Drug: Tremelimumab immunotherapy	Phase 2

Detailed Description:

A global open-label, prospective, multi-center, randomized, Phase II trial with two treatment arms designed to assess the safety and efficacy of TheraSphere administered before initiation of Durvalumab with Tremelimumab in HCC patients not eligible for or who have declined treatment with resection and/or ablation or liver transplant.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 150 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment

Intervention Model Description

Randomization will be in a 1:1 ratio for the two arms of the study. Patients will be stratified according to

• Intended TheraSphere administration method (ablative versus non ablative).
• AFP value (>400 vs ≤400 ng/ mL) at screening.

• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label, Prospective, Multi-Center, Randomized Clinical Trial to Evaluate The Efficacy and Safety Of TheraSphere Followed by Durvalumab (Imfinzi®) With Tremelimumab, Versus TheraSphere Alone For Hepatocellular Carcinoma (HCC)
• Estimated Study Start Date: May 2023
• Estimated Primary Completion Date: May 2027
• Estimated Study Completion Date: May 2028

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: TheraSphere alone; Treatment with TheraSphere	Device: TheraSphere Y-90 glass microsphere therapy; TheraSphere Y-90 glass microsphere therapy administered through the hepatic artery at index procedure.
Experimental: TheraSphere followed by Durvalumab and Tremelimumab; TheraSphere followed by Tremelimumab plus Durvalumab administered once, then repeated administration of Durvalumab monthly up 18 months post randomization	Device: TheraSphere Y-90 glass microsphere therapy; TheraSphere Y-90 glass microsphere therapy administered through the hepatic artery at index procedure.; Drug: Durvalumab (Imfinzi) immunotherapy; 1500 mg, every 4 weeks that continues for a maximum duration of 18 months or until confirmed progression (by site assessment), unacceptable toxicity, study withdrawal, or study early termination by the sponsor. Treatment beyond confirmed radiographic progression is permitted per patient consent if the following criteria are met: Absence of clinical symptoms or signs indicating clinically significant disease progression; No decline in performance status; Absence of rapid disease progression or threat to vital organs or critical anatomical sites (i.e. new CNS metastasis, respiratory failure due to tumor compression, spinal cord compression) requiring urgent alternative medical intervention; No other treatment discontinuation criteria are met; Drug: Tremelimumab immunotherapy; 300 mg, single administration

Outcome Measures

Primary Outcome Measures :

1. Objective Response Rate (ORR) [ Time Frame: Randomization (Day 1) up to subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or study termination (18 months after the last patient is randomized) ]
   Complete response and partial response evaluated by localized modified Response evaluation Criteria in Solid Tumors (mRECIST).
2. Duration of response (DoR) [ Time Frame: Time of response up to progression, subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or study termination (18 months after the last patient is randomized) ]
   According to localized mRECIST.

Secondary Outcome Measures :

1. Number of adverse events (AEs) and serious adverse events (SAEs). [ Time Frame: Treatment Day up to participant's death, opposition to data collection, lost to follow-up, or study termination (18 months after the last patient is randomized). ]
2. Number of immune mediated AEs and SAEs. [ Time Frame: Treatment Day up to participant's death, opposition to data collection, lost to follow-up, or study termination (18 months after the last patient is randomized). ]
3. Number of patients whose durvalumab and/or tremelimumab treatment was temporarily halted, postponed or permanently discontinued due to an AE. [ Time Frame: Treatment Day up to participant's death, opposition to data collection, lost to follow-up, or study termination (18 months after the last patient is randomized). ]
4. Change from baseline in liver function tests (aspartate aminotransferase [AST], alanine aminotransferase [ALT], gamma-glutamyl transpeptidase [GGT], alkaline phosphatase [ALK], bilirubin, albumin). [ Time Frame: Baseline up to participant's death, opposition to data collection, lost to follow-up, or study termination (18 months after the last patient is randomized). ]
5. Change from baseline in Child-Pugh score. [ Time Frame: Baseline up to participant's death, opposition to data collection, lost to follow-up, or study termination (18 months after the last patient is randomized). ]
   Minimum value is 5 (better) and maximum value is 15 (worse).
6. Change from baseline in Albumin Bilirubin (ALBI) score. [ Time Frame: Baseline up to participant's death, opposition to data collection, lost to follow-up, or study termination (18 months after the last patient is randomized). ]
   Minimum value is 1 (better) and maximum value is 3 (worse).
7. Change from baseline in Eastern Cooperative Oncology Group (ECOG) score. [ Time Frame: Baseline up to participant's death, opposition to data collection, lost to follow-up, or study termination (18 months after the last patient is randomized). ]
   Minimum value is 0 (better) and maximum value is 5 (worse).
8. ORR according to mRECIST, RECIST 1.1. [ Time Frame: Randomization (Day 1) up to subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or study termination (18 months after the last patient is randomized). ]
9. DoR according to mRECIST, RECIST 1.1. [ Time Frame: Time of response up to progression, subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or study termination (18 months after the last patient is randomized). ]
10. Disease Control Rate (DCR) according to localized mRECIST, mRECIST, RECIST 1.1. [ Time Frame: Randomization (Day 1) up to subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or study termination (18 months after the last patient is randomized). ]
11. Duration of disease control (DoDC) according to localized mRECIST, mRECIST, RECIST 1.1. [ Time Frame: Time of disease control up to subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or study termination (18 months after the last patient is randomized). ]
12. Time to best response (CR or PR) according to localized mRECIST, mRECIST, RECIST 1.1. [ Time Frame: Randomization (Day 1) up to best response (CR or PR), subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or study termination (18 months after the last patient is randomized). ]
13. Complete response rate (CRR) according to localized mRECIST, mRECIST, RECIST 1.1. [ Time Frame: Randomization (Day 1) up to complete response, subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or study termination (18 months after the last patient is randomized). ]
14. Duration of complete response (DoCR) according to localized mRECIST, mRECIST, RECIST 1.1. [ Time Frame: Time of complete response up to subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or study termination (18 months after the last patient is randomized). ]
15. Hepatic time to progression (hTTP) according to mRECIST, RECIST 1.1. [ Time Frame: Randomization (Day 1) up to hepatic progression, subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or study termination (18 months after the last patient is randomized). ]
16. Time to progression (TTP) according to localized mRECIST, mRECIST, RECIST 1.1. [ Time Frame: Randomization (Day 1) up to progression, subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or study termination (18 months after the last patient is randomized). ]
17. Progression free survival (PFS) according to localized mRECIST, mRECIST, RECIST 1.1; this will include an evaluation of the PFS rate at 6, 12, 18 and 24 months. [ Time Frame: Randomization (Day 1) up to progression, subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or study termination (18 months after the last patient is randomized). ]
18. Hepatic progression free survival (hPFS) by mRECIST, RECIST 1.1. [ Time Frame: Randomization (Day 1) up to hepatic progression, subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or study termination (18 months after the last patient is randomized). ]
19. Overall survival (OS). [ Time Frame: Randomization (Day 1) up to participant's death, opposition to data collection, lost to follow-up, or study termination (18 months after the last patient is randomized). ]
20. Proportion of patients receiving subsequent treatment for HCC after study treatment, and type of HCC treatment received. [ Time Frame: Randomization (Day 1) up to participant's death, opposition to data collection, lost to follow-up, or study termination (18 months after the last patient is randomized). ]
21. Proportion of patients to undergo curative therapy (transplantation or resection). [ Time Frame: Randomization (Day 1) up to participant's death, opposition to data collection, lost to follow-up, or study termination (18 months after the last patient is randomized). ]
22. Time to subsequent HCC treatment (local or systemic therapy). [ Time Frame: Randomization (Day 1) up to subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or study termination (18 months after the last patient is randomized). ]
23. Reason for starting subsequent HCC treatment. [ Time Frame: Randomization (Day 1) up to subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or study termination (18 months after the last patient is randomized). ]
24. Alpha fetoprotein (AFP) response. [ Time Frame: Baseline up to subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or study termination (18 months after the last patient is randomized). ]
25. Change from baseline in quality of life (QoL) by FACT-Hep. [ Time Frame: Baseline up to participant's death, opposition to data collection, lost to follow-up, or study termination (18 months after the last patient is randomized). ]
26. Change from baseline in QoL by EQ-5D. [ Time Frame: Baseline up to participant's death, opposition to data collection, lost to follow-up, or study termination (18 months after the last patient is randomized). ]
27. Pre-treatment volumes and absorbed doses to the following volumes of interest (VOIs) using 99mTc-MAA SPECT/CT imaging and Simplicit90Y dosimetry software will be determined. [ Time Frame: Baseline Visit ]

    Only tumor ≥3cm of longest diameter should be considered for dosimetry assessment.

    a. Tumoral VOIs i. All Tumor(s) ii. Target lesion(s) according to mRECIST b. Perfused Liver VOI c. Normal liver tissue VOIs i. Perfused normal tissue ii. Whole liver normal tissue

28. Post-treatment volumes and absorbed doses to the following volumes of interest (VOIs) using Y-90 PET imaging and Simplicit90Y dosimetry software will be determined. [ Time Frame: Treatment Visit ]

    Only tumor ≥3cm of longest diameter should be considered for dosimetry assessment.

    a. Tumoral VOIs i. All Tumor(s) ii. Target lesion(s) according to mRECIST b. Perfused Liver VOI c. Normal liver tissue VOIs i. Perfused normal tissue ii. Whole liver normal tissue

29. Correlation between tumoral absorbed doses in Gy, determined by 99mTc-MAA SPECT/CT, assessing impact on tumor response, survival and number of Grade 3 or higher AEs and SAEs. [ Time Frame: Randomization (Day 1) up to subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or study termination (18 months after the last patient is randomized). ]
30. Correlation between normal tissue absorbed doses in Gy, determined by 99mTc-MAA SPECT/CT, assessing impact on tumor response, survival and number of Grade 3 or higher AEs and SAEs. [ Time Frame: Randomization (Day 1) up to subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or study termination (18 months after the last patient is randomized). ]
31. Correlation between tumoral absorbed doses in Gy, determined by Y-90 PET, assessing impact on tumor response, survival and number of Grade 3 or higher AEs and SAEs. [ Time Frame: Randomization (Day 1) up to subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or study termination (18 months after the last patient is randomized). ]
32. Correlation between normal tissue absorbed doses in Gy, determined by Y-90 PET, assessing impact on tumor response, survival and number of Grade 3 or higher AEs and SAEs. [ Time Frame: Randomization (Day 1) up to subsequent anti-cancer therapy, participant's death, opposition to data collection, lost to follow-up, or study termination (18 months after the last patient is randomized). ]
33. Correlation between tumoral absorbed doses in Gy determined by 99mTc-MAA SPECT/CT and Y-90 PET. [ Time Frame: Baseline up to post-treatment imaging visit. ]
34. Correlation between normal tissue absorbed doses in Gy determined by 99mTc-MAA SPECT/CT and by Y-90 PET. [ Time Frame: Baseline up to post-treatment imaging visit. ]
35. Determination of dose volume histogram (DVH) for tumoral VOIs and normal liver tissue VOIs, using 99mTc-MAA SPECT/CT and Y-90 PET. [ Time Frame: Baseline up to post-treatment imaging visit. ]
36. Whole liver and remnant liver volumes at baseline and follow-up imaging assessments measured using Simplicit90Y software. [ Time Frame: Randomization (Day 1) up to participant's death, opposition to data collection, lost to follow-up, or study termination (18 months after the last patient is randomized). ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Participants must be aged ≥18 years at the time of screening.
2. Written informed consent and any locally required authorization (e.g., Health Insurance Portability and accountability Act in the US, European Union (EU) data privacy regulations in the EU) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.
3. Life expectancy ≥6 months.
4. HCC, diagnosed by radiographic imaging or histology.
5. Patient not a candidate for liver resection, thermal ablation, or transplantation at the time of study entry.
6. Treatment naïve.
7. Measurable disease by mRECIST criteria (e.g. ≥10mm of enhancement).
8. Tumor volume ≤25% of whole liver volume (determined by imaging).
9. Unilobar tumor
10. Future liver remnant volume (FLRV) ≥30% of whole liver volume. FRLV is the volume of liver not planned to be treated with TheraSphere and free of HCC.

11. Patients with HBV or HCV infection are to have documented virology status of hepatitis as confirmed by HBV and HCV serology test:

    1. Patients with HBV infection: HBV DNA load should be ≤2000 IU/mL obtained within 28 days prior to initiation of study treatment, and Anti-HBV treatment (per local standard of care; e.g., entecavir) for a minimum of 14 days prior to study entry and willingness to continue treatment for the length of the study
    2. Patients with chronic HCV infection are allowed in the study: for untreated patients, AST/ALT should be ≤3xULN and for treated patients, antiviral treatment (per local standard of care) should be stopped for a minimum of 14 days prior to study entry and AST/ALT should be ≤3xULN
12. Patient with Human Immunodeficiency Virus (HIV) infection is eligible with well controlled HIV infection, no current or previous AIDS-related complications and CD4+ T-cell (CD4+) counts ≥ 350 cells/uL
13. Negative serum pregnancy test in females of child-bearing potential; patients who are breast-feeding cannot participate in this trial.
14. Adequate contraception for the patient and his/her sexual partner.

15. Adequate renal and marrow function as defined below:

    1. Hemoglobin ≥9.0 g/dL
    2. Absolute neutrophil count ≥1.5 x 109/L
    3. Platelet count ≥75 x 109/L
    4. Measured or calculated creatinine clearance ≥45 mL/min as determined by Cockcroft-Gault (using actual body weight)
16. Absolute lymphocyte count ≥1.0 X 109/L

17. Adequate liver function, as defined by

    1. Child-Pugh A
    2. Serum albumin ≥30 g/L
    3. Serum bilirubin <1.1 x the upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert's syndrome, who will be permitted to enroll in the study in consultation with their physician.
    4. AST and ALT <3 x ULN.
18. Eastern Cooperative Oncology Group (ECOG) performance status of 0 at randomization.
19. Body weight >30 kg and BMI ≥18 kg/m2.

Exclusion Criteria:

1. Any contraindication to angiography or selective visceral catheterization.
2. Cone Beam CT (CBCT) or Technetium-99m macroaggregated Albumin (99mTc-MAA) hepatic arterial perfusion scintigraphy shows any deposition to the gastrointestinal tract that may not be corrected by angiographic techniques.
3. CBCT or 99mTc-MAA hepatic arterial perfusion scintigraphy shows poor tumor targeting that would lead to a dose that does not meet the protocol specified liver dosing criteria, if lobar administration with multi-compartment dosimetry is planned.
4. Shunting of blood to the lungs that could result in delivery of >30 Gy to the lungs in a single treatment or >50 Gy cumulative dose to the lungs in case of multiple TheraSphere treatments, as seen on 99mTc-MAA hepatic arterial perfusion scintigraphy.
5. Extrahepatic metastases, including patients with hilar /mesenteric /celiac lymph nodes >1.5 cm in shorter axis, or with lung nodules (single lesion, > 1 cm, or multiple smaller lesions with a total diameter >2 cm)
6. Brain metastases, leptomeningeal carcinomatosis or spinal cord compression. Patients with suspected brain metastases at screening should have an MRI (preferred) or CT each preferably with IV contrast of the brain prior to study entry.
7. Evidence of any tumor vascular invasion.
8. Any prior treatment for HCC including surgery, TACE/TAE, ablation, systemic, and/or radiation treatment (including radiation treatment to the liver for any diagnosis).
9. Prior exposure to any immune mediated therapy, including but not limited to other anti PD-1, anti-PDL-1, anti-PDL2, anti-CTLA-4, antibodies, IFN.
10. Concurrent treatment for HCC or treatment in the last 4 weeks in another clinical study, unless it is an observational study (non-interventional) or during a non-interventional follow-up stage of an interventional study, or prior randomization to this study
11. Hepatic encephalopathy present at study entry and/or episodes of encephalopathy (≥Grade 2) within 6 months prior to randomization.
12. Presence of ascites, clinical or radiological, "trace" of ascites is acceptable.
13. HCC with infiltrative disease presentation that is not possible to evaluate by mRECIST.
14. History of active primary/acquired immunodeficiency.
15. Evidence of pulmonary insufficiency (defined by an arterial oxygen pressure (Pa,O2) of <60 mmHg, or oxygen saturation (Sa,O2) of <90% (Roussos & Koutsoukou, 2003) or clinically evident chronic obstructive pulmonary disease (COPD).
16. Medical history of radiation pneumonitis or recent pneumonitis, regardless of causality
17. History of any organ allograft, including bone marrow allo and autograft.

18. Active or prior documented autoimmune or inflammatory disorders (including but not limited to, inflammatory bowel disease [e.g. ulcerative colitis or Crohn's disease], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion:

    1. Patients with vitiligo or alopecia
    2. Patients with hypothyroidism (e.g. following Hashimoto's syndrome) stable on hormone replacement therapy
    3. Any chronic skin condition that does not require systemic therapy.
    4. Patients without active disease in the last 5 years may be included but only after consultation with the Sponsor Study physician.
    5. Patients with celiac disease controlled by diet alone.

19. Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion:

    1. Intranasal, inhaled, topical steroids, or local steroid injections (e.g. intra-articular injection)
    2. Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent.
    3. Steroids as premedication for hypersensitivity reactions (e.g. CT scan premedication).
20. History of gastrointestinal bleeding within 28 days prior to randomization, active GI bleeding and any bleeding diathesis or coagulopathy that is not correctable by usual therapy or hemostatic agents (e.g. closure device). Patients with known varices that have not bled can enter the study. No endoscopic exploration is required before randomization.
21. Presence of biliary stent at any time or sphincterotomy within one year prior to randomization.
22. History of malignancy, other than HCC, within three years, with the exception if adequately treated carcinoma in situ of the cervix, early squamous cell carcinoma or basal cell carcinoma of the skin, localized prostate cancer, ductal carcinoma in situ, or low grade endometrial carcinoma with no myometrial invasion (negligible risk of metastases or death 5-year OS rate >90%).
23. Major surgical procedure (as defined by the Investigator) within 28 days prior to randomization.
24. A history of severe allergy or intolerance to contrast agents, narcotics, sedatives or atropine that cannot be managed medically.
25. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
26. Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis testing in line with local practice), HBV and HVC co-infection, HBV and Hep D co-infection, or human immunodeficiency virus (HIV 1/2 antibodies) plus HCV or HBV co-infection.
27. Receipt of live attenuated vaccine within 30 days prior to the first dose of durvalumab and/or tremelimumab. Note: patients, if enrolled, should not receive live vaccine whilst receiving durvalumab and/or tremelimumab and up to 30 days after the last dose of durvalumab and/or tremelimumab.
28. Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab and tremelimumab monotherapy.
29. Unstable chronic disease or evidence of any disease or condition that would place the patient at undue risk and preclude safe use of TheraSphere, durvalumab and tremelimumab treatment, including but not limited to, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, active interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.
30. Patient not able to follow the TheraSphere, durvalumab or tremelimumab treatment requirements.

Contacts and Locations

Locations

United States, District of Columbia

Georgetown University

Washington, District of Columbia, United States, 20007

MedStar Washington Hospital Center

Washington, District of Columbia, United States, 20010

United States, Florida

Mayo Clinic

Jacksonville, Florida, United States, 32224

United States, Illinois

Rush University Medical Center

Chicago, Illinois, United States, 60612

United States, Indiana

Indiana University

Indianapolis, Indiana, United States, 46202

United States, Minnesota

University of Minnesota

Minneapolis, Minnesota, United States, 55455

United States, New York

NYU Langone Health

New York, New York, United States, 10016

Spain

Hospital Universitario Central de Asturias

Oviedo, Asturias, Spain

Clinica Universidad de Navarra

Pamplona, Navarre, Spain, 31008

Sponsors and Collaborators

Boston Scientific Corporation

Biocompatibles UK Ltd

Investigators

• Principal Investigator: Beau Toskich, MD; Mayo Clinic
• Principal Investigator: Aiwu Ruth He, MD PhD; Georgetown University

More Information

• Responsible Party: Boston Scientific Corporation
• ClinicalTrials.gov Identifier: NCT05063565
• Other Study ID Numbers: S2472
• First Posted: October 1, 2021
• Last Update Posted: March 20, 2023
• Last Verified: March 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: Yes

Keywords provided by Boston Scientific Corporation:

Carcinoma; Carcinoma, Hepatocellular; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Additional relevant MeSH terms:

Carcinoma; Carcinoma, Hepatocellular; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Durvalumab; Tremelimumab; Immunologic Factors; Antineoplastic Agents, Immunological; Antineoplastic Agents; Physiological Effects of Drugs