Phase 2 Study of Durvalumab plus Tremelimumab with Lenvatinib versus Durvalumab plus Tremelimumab in Patients with Unresectable Hepatocellular Carcinoma

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What is this study about?

The trial focuses on patients with unresectable hepatocellular carcinoma, a type of liver cancer that cannot be removed by surgery. It evaluates a combination of two intravenous medicines, durvalumab and tremelimumab, together called STRIDE, and adds an oral pill called lenvatinib in one group, while another group receives only the STRIDE combination.

The purpose of the study is to compare how long the cancer stays under control, measured as progression‑free survival, between the two treatment approaches.

Participants receive a series of IV infusions of the STRIDE drugs every few weeks, with the lenvatinib group also taking a daily capsule. The treatment period lasts several months, during which doctors perform regular scans and health checks to monitor the cancer and any side effects. Outcomes such as overall survival, objective response rate, safety and toxicity are recorded.

1 initial treatment day

on the first day after joining the study, receive an intravenous infusion of tremelimumab at a dose of 300 mg and an intravenous infusion of durvalumab at a dose of 1500 mg.

the same day, begin taking oral lenvatinib capsules, each containing 12 mg.

2 daily oral medication

take one lenvatinib capsule by mouth each day, continuing as instructed until the study protocol indicates a stop.

3 repeat intravenous infusions

receive additional intravenous doses of durvalumab 1500 mg and tremelimumab 300 mg according to the study schedule, which is defined by the trial protocol.

4 regular follow‑up visits

attend scheduled clinic visits for safety assessments, blood tests, and imaging studies to monitor disease status and treatment effects.

5 completion of treatment

stop all study medications when the protocol specifies the end of treatment, and undergo a final evaluation to document outcomes.

Who Can Join the Study?

You must be 18 years old or older.
You must weigh more than 30 kg (about 66 lb).
You must have a life expectancy of at least 12 weeks.
You must have a confirmed diagnosis of liver cancer (hepatocellular carcinoma). This can be proven by a tissue test (histopathology) or by meeting the imaging criteria set by the American Association for the Study of Liver Diseases (AASLD), which includes a scan showing at least one lesion classified as LI‑RADS 5 (a very likely cancer).
You must not have received any previous whole‑body (systemic) treatment for liver cancer.
You must not be a candidate for local (regional) treatments such as surgery, ablation, or other procedures aimed at the tumor. If you previously had such a treatment, it must have been finished at least 28 days before the study’s baseline scan.
Your liver cancer must be classified as stage B (not eligible for local treatment) or stage C according to the Barcelona Clinic Liver Cancer (BCLC) staging system.
Your liver function must be rated as Child‑Pugh class A or class B7 (based on a low albumin level of 25‑27 g/L).
Your overall health and activity level must be scored as 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance‑status scale.
You must have at least one tumor that can be measured on a scan. The tumor must be at least 10 mm in its longest dimension (or a lymph node must be at least 15 mm in short axis) on a CT or MRI scan, and it must be suitable for repeated measurements according to the RECIST 1.1 guidelines.
If you have an active hepatitis B virus (HBV) infection (positive HBV surface antigen or core antibodies with detectable HBV DNA ≥ 10 IU/mL), you must be on antiviral medication before joining the study, continue it during the study, and keep it for 6 months after the last dose. If your HBV DNA is undetectable, you do not need antiviral medication before enrollment, but you will be tested regularly and start treatment if the virus becomes detectable.

Who Cannot Join the Study?

Having had any other type of cancer in the past, unless it was a non‑melanoma skin cancer, a cervical cancer that was treated early (in‑situ), or another cancer that was completely cured and has had no signs of disease for at least five years.
Currently receiving chemotherapy, any other study drug, or cancer‑related biologic or hormone treatments (using hormone replacement therapy for non‑cancer reasons is allowed).
Having special forms of liver cancer such as fibrolamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, infiltrative‑type hepatocellular carcinoma, or a mixed tumor that includes cholangiocarcinoma and hepatocellular carcinoma.
Having significant fluid buildup in the abdomen (ascites) that needed a procedure like paracentesis (draining fluid) within the past six months. If the fluid was only treated with diuretics (medicines that help remove excess fluid) and the dose has been stable for at least two months, you may be eligible.
Having uncontrolled high blood pressure (systolic ≥ 150 mm Hg or diastolic ≥ 90 mm Hg) despite standard medical treatment.
Having previously been treated with drugs that block PD‑1 or PD‑L1 (immune checkpoint proteins) such as durvalumab, or with drugs that block CTLA‑4 such as tremelimumab.
Having a history of primary immunodeficiency (a condition where the immune system does not work properly), having received an organ transplant, or having experienced severe (grade 3 or 4) immune‑related side effects from earlier immune therapies.
Testing positive for human immunodeficiency virus (HIV) or having an active tuberculosis infection (a bacterial lung disease that can spread).
Being allergic or overly sensitive (hypersensitivity) to any of the study medicines or any of their inactive ingredients.
Using medicines that suppress the immune system within 28 days before the first study dose, except for nasal or inhaled steroids, or low‑dose oral steroids (no more than 10 mg per day of prednisone or an equivalent).
Having an active autoimmune or inflammatory disorder such as inflammatory bowel disease (Crohn’s disease or ulcerative colitis), diverticulitis, systemic lupus erythematosus, sarcoidosis, granulomatosis with polyangiitis (formerly Wegener’s), Graves’ disease, rheumatoid arthritis, hypophysitis, or uveitis, unless the condition is one of the listed exceptions (e.g., vitiligo, stable hypothyroidism, controlled celiac disease, etc.).

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country	Status
Azienda Ospedaliera Universitaria Universita’ Degli Studi Della Campania Luigi Vanvitelli	Naples	Italy

Other Sites

Site Name	City	Country
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico	Milan	Italy
Universita’ Campus Bio-medico Di Roma	Rome	Italy
Universita’ Politecnica Delle Marche	Ancona	Italy
IRCCS Istituto Nazionale Tumori Fondazione Pascale	Naples	Italy
Azienda Sanitaria Locale Napoli 1 Centro	Naples	Italy
Azienda Ospedaliera Universitaria Di Cagliari	Monserrato	Italy
Azienda Ospedaliero Universitaria Pisana	Pisa	Italy
Abytctu Onmexjpnnfp Uhgqqnvpqnrsz Cwezlbcdesvc Dhqdg Skjvqf E Dgzbn Sxrlpgn Dc Txokqx	Turin	Italy

Trial status

Country	Status	Recruitment Start
Italy	Not yet recruiting	01.08.2026

Trial locations

Investigated drugs:

Durvalumab is a medication given through an IV that helps the body’s immune system see and attack cancer cells. In this study it is used together with another drug as part of a combination called STRIDE, aiming to boost the immune response against liver cancer.

Tremelimumab is also administered by IV and works by blocking a protein that can keep the immune system from fighting cancer effectively. When combined with durvalumab in the STRIDE regimen, it is intended to further enhance the body’s ability to target tumor cells.

Lenvatinib is an oral pill that blocks several signals that tumors use to grow and create new blood vessels. In the trial it is tested alongside the STRIDE combination to see if adding this drug can keep the cancer from progressing for a longer time.

Hepatocellular carcinoma – Hepatocellular carcinoma is a type of liver cancer that begins in the main liver cells called hepatocytes. It often develops in people who have long‑term liver disease such as cirrhosis or hepatitis. When the tumor cannot be removed by surgery, it is called unresectable. The cancer can grow within the liver, forming new nodules and may spread to nearby blood vessels. Over time, the tumor may enlarge and affect liver function, leading to worsening symptoms.

Trial ID:

2025-521608-23-00

Protocol code:

HE.2

Trial Phase:

Therapeutic exploratory (Phase II)

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Phase 2 Study of Durvalumab plus Tremelimumab with Lenvatinib versus Durvalumab plus Tremelimumab in Patients with Unresectable Hepatocellular Carcinoma

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?