STRIDE (Durvalumab + Tremelimumab) With Lenvatinib vs STRIDE Alone in Unresectable Hepatocellular Carcinoma

NCT06880523 | Recruiting Phase 2 DMC

• 1 other identifier: HE2
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 11

Brief Summary

The purpose of this study is to compare the effects on participants' and liver cancer by adding a drug that is used on its own to treat this disease to a combination of two other drugs which is also used to treat liver cancer, compared to the two-drug combination alone.

Conditions

Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival using RECIST 1.1

  32 months

Secondary Outcomes (3)

• Overall Survival

  32 months

• Number and Severity of Adverse Events using CTCAE

  32 months

• Objective Response Rate using RECIST 1.1

  32 months

Study Arms (2)

STRIDE (durvalumab + tremelimumab)

ACTIVE COMPARATOR

Drug: STRIDE (durvalumab + tremelimumab); Drug: Durvalumab

STRIDE (durvalumab + tremelimumab) + Lenvatinib

EXPERIMENTAL

Drug: STRIDE (durvalumab + tremelimumab); Drug: Lenvatinib

Interventions

Durvalumab DRUG

monotherapy every 4 weeks

STRIDE (durvalumab + tremelimumab)

Lenvatinib DRUG

Daily

STRIDE (durvalumab + tremelimumab) + Lenvatinib

STRIDE (durvalumab + tremelimumab) DRUG

As first treatment

STRIDE (durvalumab + tremelimumab); STRIDE (durvalumab + tremelimumab) + Lenvatinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years.
• Body weight \> 30 kg.
• Life expectancy of at least 12 weeks.
• Confirmed HCC based on histopathological findings from tumour tissues or clinically by AASLD criteria in cirrhotic participants.
• Must not have received prior systemic therapy for HCC.
• 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.
• Barcelona Clinic Liver Cancer (BCLC) stage B (that is not eligible for locoregional therapy) or stage C.
• Child-Pugh Score class A or B7 based on low albumin (albumin 25-27 g/L) only.
• Must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• 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.
• 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 (eg, 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).

You may not qualify if:

• 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.
• 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.
• Known fibrolamellar HCC, sarcomatoid HCC, infiltrative-type HCC or mixed cholangiocarcinoma and HCC.
• Clinically meaningful ascites, defined as ascites requiring non-pharmacologic intervention
• 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.
• Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab, or an anti-CTLA4, including tremelimumab.
• History of primary immunodeficiency, history of organ transplant or prior history of severe (grade 3 or 4) immune mediated toxicity from other immune therapy.
• 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).
• Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
• Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab or tremelimumab
• 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.
• Patients with active or uncontrolled intercurrent illness
• History of leptomeningeal carcinomatosis.
• Symptomatic or uncontrolled brain metastases requiring concurrent treatment, inclusive of but not limited to surgery, radiation and/or corticosteroids.
• Major surgical procedure (as defined by the Investigator) within 28 days prior to enrollment.

Sponsors & Collaborators

• AstraZeneca: collaborator
• Canadian Cancer Trials Group: lead
• National Cancer Institute, Naples: collaborator

Study Sites (11)

Arthur J.E. Child Comprehensive Cancer Centre

Calgary, Alberta, T2N 5G2, Canada

RECRUITING

BCCA - Vancouver

Vancouver, British Columbia, V5Z 4E6, Canada

RECRUITING

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, L8V 5C2, Canada

RECRUITING

Kingston Health Sciences Centre

Kingston, Ontario, K7L 2V7, Canada

RECRUITING

Waterloo Regional Health Network (WRHN)

Kitchener, Ontario, N2G 1G3, Canada

RECRUITING

London Health Sciences Centre Research Inc.

London, Ontario, N6A 5W9, Canada

RECRUITING

Trillium Health Partners - Credit Valley Hospital

Mississauga, Ontario, L5M 2N1, Canada

RECRUITING

Ottawa Hospital Research Institute

Ottawa, Ontario, K1H 8L6, Canada

RECRUITING

University Health Network

Toronto, Ontario, M5G 2M9, Canada

RECRUITING

CHUM-Centre Hospitalier de l'Universite de Montreal

Montreal, Quebec, H2X 3E4, Canada

RECRUITING

The Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

durvalumab; tremelimumab; lenvatinib

Condition Hierarchy (Ancestors)

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

Study Officials

• Vincent Tam

  Arthur J.E. Child Comprehensive Cancer Centre, Calgary AB, Canada

  STUDY CHAIR

• Jennifer Knox

  University Health Network-OCI/Princess Margaret Hospital, Toronto, ON Canada

  STUDY CHAIR

• Marilina Piccirillo

  NCI-Naples, Italy

  STUDY CHAIR

Central Study Contacts

Chris O'Callaghan

CONTACT

613-533-6430; cocallaghan@ctg.queensu.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2025
• First Posted: March 17, 2025
• Study Start: October 21, 2025
• Primary Completion (Estimated): January 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: April 14, 2026

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

CA (11)