A PHASE 2 STUDY OF STRIDE (durvalumab + tremelimumab) With Lenvatinib Versus STRIDE Alone in Patients With Unresectable Hepatocellular Carcinoma (SLIDE-HCC) - HE.2

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• 4.2.1 Participants with a history of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other tumours curatively treated with no evidence of disease for ≥ 5 years. 4.2.2 Any concurrent chemotherapy, study drug, or biologic or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g. hormone replacement therapy) is acceptable. 4.2.3 Known fibrolamellar HCC, sarcomatoid HCC, infiltrative-type HCC or mixed cholangiocarcinoma and HCC. 4.2.4 Clinically meaningful ascites, defined as ascites requiring non-pharmacologic intervention (e.g. paracentesis) to maintain symptomatic control, within 6 months prior to the first scheduled dose. Participants with ascites that has required pharmacologic intervention (e.g. diuretics) and who have been on stable doses of diuretics for ascites for ≥ 2 months are eligible. 4.2.5 Uncontrolled arterial hypertension defined by a systolic pressure ≥ 150 mm Hg or diastolic pressure ≥ 90 mm Hg or other hypertensive cardiovascular complications despite standard medical management. 4.2.6 Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab, or an anti-CTLA4, including tremelimumab. 4.2.7 History of primary immunodeficiency, history of organ transplant or prior history of severe (grade 3 or 4) immune mediated toxicity from other immune therapy. 4.2.8 Known to have tested positive for human immunodeficiency virus (HIV) (positive HIV 1/2 antibodies) or active tuberculosis infection (clinical evaluation that may include clinical history, physical examination and radiographic findings, or tuberculosis testing in line with local practice). 4.2.9 Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients. 4.2.10 Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab or tremelimumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. 4.2.11 Active or prior documented autoimmune or inflammatory disorders including inflammatory bowel disease (e.g. Crohn’s disease, ulcerative colitis), diverticulitis (with the exception of diverticulosis), 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: vitiligo; alopecia; hypothyroidism (e.g. following Hashimoto syndrome) stable on hormone replacement; any chronic skin condition that does not require systemic therapy; celiac disease controlled by diet alone; Graves’ disease if no treatment was required within 2 years prior to enrollment. Otherwise, patients without active disease in the last 5 years may be included but only after consultation with the study physician. See the protocol for other criteria

• 4.1.1 Age ≥ 18 years. 4.1.2 Body weight > 30 kg. 4.1.3 Life expectancy of at least 12 weeks. 4.1.4 Confirmed HCC based on histopathological findings from tumour tissues or clinically by AASLD criteria [Singal 2023] in cirrhotic participants. Note: Participants diagnosed based on AASLD criteria only must have corresponding source documentation available which confirms these criteria have been met. This includes imaging documentation of at least one LI-RADS 5 lesion. 4.1.5 Must not have received prior systemic therapy for HCC. 4.1.6 Must not be eligible for locoregional therapy for unresectable HCC. For patients who progressed after locoregional therapy for HCC, locoregional therapy must have been completed ≥28 days prior to the baseline scan of the abdomen and pelvis for the current study. 4.1.7 Barcelona Clinic Liver Cancer (BCLC) stage B (that is not eligible for locoregional therapy) or stage C. 4.1.8 Child-Pugh Score class A or B7 based on low albumin (albumin 25-27 g/L) only. 4.1.9 Must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 4.1.10 At least 1 measurable lesion, not previously irradiated, that can be accurately measured at baseline as ≥10 mm in the longest diameter (except lymph nodes, which must have a short axis ≥15 mm) with computerized tomography (CT) or magnetic resonance imaging (MRI), and that is suitable for accurate repeated measurements as per RECIST 1.1 guidelines. A lesion which progressed after previous ablation or TACE could be measurable if it meets these criteria. PROTOCOL DATE: 2025-MAR-17 CCTG TRIAL: HE.2 CONFIDENTIAL 14 CONFIDENTIAL 4.1.11 Participants with active HBV infection [characterized by positive hepatitis B virus surface antigen (HBsAg) and/or positive hepatitis B core antibodies (anti-HBcAb) with detectable HBV deoxyribonucleic acid (DNA) (≥10 IU/mL or above the limit of detection per local lab standard)] are eligible if: • The participant is being treated with antiviral therapy, as per institutional practice. The HBV antiviral therapy must be initiated prior to randomization, and the participant must remain on antiviral therapy for the study duration and for 6 months after the last dose of study medication. • The participant must show evidence of HBV stabilization or signs of viral response (e.g. reduction of HBV DNA levels) prior to enrollment Participants who test positive for HBsAg or anti-hepatitis B core (HBc) with undetectable HBV DNA (< 10 IU/mL or under the limit of detection per local lab standard) are eligible and do not require antiviral therapy prior to randomization. • These participants will be tested at every cycle to monitor HBV DNA levels and initiate antiviral therapy if HBV DNA is detected (≥ 10 IU/mL or above the limit of detection per local lab standard). • If HBV DNA becomes detectable during study treatment, antiviral therapy must be initiated, and the participant must remain on antiviral therapy during the study treatment period and for 6 months after the last dose of study medication. See the protocol for other criteria