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RecruitingNCT05168163Updated Aug 4, 2026

Atezolizumab in Combination With a Multi-Kinase Inhibitor for the Treatment of Unresectable, Locally Advanced, or Metastatic Liver Cancer

A Phase 2 interventional study of Atezolizumab and Cabozantinib in Locally Advanced Hepatocellular Carcinoma, Metastatic Hepatocellular Carcinoma and Stage III Hepatocellular Carcinoma AJCC v8, sponsored by Academic and Community Cancer Research United. Recruiting at 16 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-08-04.

Sponsored by Academic and Community Cancer Research United · Phase 2, Interventional, and Treatment

From the registry’s dates

  • Started May 2022; still recruiting 4 years 5 months later.
Phase
Phase 2
Study type
Interventional
Enrollment
122
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

This phase II trial tests whether atezolizumab in combination with a multi-kinase inhibitor (cabozantinib or lenvatinib) compared to multi-kinase inhibitor alone in treating patients with liver cancer that cannot be removed by surgery (unresectable), has spread to has spread to nearby tissue or lymph nodes (locally advanced), or has spread to other places in the body (metastatic), for which the patient has received treatment in the past (previously treated). Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Cabozantinib and lenvatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving atezolizumab with cabozantinib or lenvatinib may kill more tumor cells in patients with liver cancer.

Read the detailed description

PRIMARY OBJECTIVE:

I. To determine the progression-free and overall survival in subjects with advanced hepatocellular carcinoma who previously progressed on atezolizumab/bevacizumab who are treated using atezolizumab plus a multi-kinase inhibitor compared to multi-kinase inhibitor alone.

SECONDARY OBJECTIVES:

I. To determine the overall response rate per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 response in subjects who are treated using atezolizumab plus a multi-kinase inhibitor compared to multi-kinase inhibitor alone.

II. To determine the duration of response in subjects who are treated using atezolizumab plus a multi-kinase inhibitor compared to multi-kinase inhibitor alone.

III. To determine the safety profile of adding atezolizumab to multi-kinase inhibitor in subjects who are treated using atezolizumab plus a multi-kinase inhibitor compared to multi-kinase inhibitor alone.

EXPLORATORY OBJECTIVE:

I. To explore for potential predictive biomarkers for response and resistance to anti-PD-L1 and/or multi-kinase inhibitor therapy in subject population.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive atezolizumab intravenously (IV) over 30-60 minutes on day 1 and cabozantinib orally (PO) once daily (QD) or lenvatinib PO QD on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive cabozantinib PO QD or lenvatinib PO QD on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed-up every 9 weeks for up to 2 years.

02

Conditions studied

  • Locally Advanced Hepatocellular Carcinoma
  • Metastatic Hepatocellular Carcinoma
  • Stage III Hepatocellular Carcinoma AJCC v8
  • Stage IIIA Hepatocellular Carcinoma AJCC v8
  • Stage IIIB Hepatocellular Carcinoma AJCC v8
  • Stage IV Hepatocellular Carcinoma AJCC v8
  • Stage IVA Hepatocellular Carcinoma AJCC v8
  • Stage IVB Hepatocellular Carcinoma AJCC v8
  • Unresectable Hepatocellular Carcinoma
03

In context

Carcinoma, Hepatocellular

3,648 studies on the registry are indexed under Carcinoma, Hepatocellular; 1,061 are open to participants now.

This study's planned enrollment of 122 is above the median of 54 across 2,618 interventional studies indexed under Carcinoma, Hepatocellular.

Browse Carcinoma, Hepatocellular studies →

Lead sponsor

Academic and Community Cancer Research United is the lead sponsor of 50 studies on the registry; 4 are open to participants now.

Of its 13 completed or terminated interventional studies of FDA-regulated products, 12 (92%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • Provide written =\< 28 days prior to randomization

  • Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study)

    • NOTE: During the Active Monitoring Phase of a study (i.e., active treatment and clinical follow-up), participants must be willing to return to the consenting institution for follow-up
  • Age >= 18 years
  • Hepatocellular carcinoma (HCC) confirmed by histological/cytological diagnosis or clinically per the American Association for the Study of Liver Diseases (AASLD) or WASL 2018 criteria
  • Locally advanced, and/or unresectable disease that is not amendable to curative treatment

  • Previously progressed on atezolizumab in combination with bevacizumab as systemic therapy for advanced disease

    • NOTE: 2nd line patients only
  • (ECOG) Performance Status 0 or 1
  • class A

  • Documented virology status of hepatitis, as confirmed by screening virus (HBV) and virus (HCV) serology tests.

    • For subjects with active HBV, HBV deoxyribonucleic acid (DNA) \< 500 IU/mL obtained ≤ =\< 28 days prior to randomization, and anti-HBV treatment (per local standard of care; e.g., entecavir) for a minimum of 14 days prior to randomization and willingness to continue treatment for the length of the study
  • At least one measurable untreated malignant lesion per v1.1. Subjects who previously received local therapy (e.g., ablation, percutaneous ethanol injection, trans-arterial embolization/chemo-embolization) are eligible provided the target lesion(s) have not been previously treated with local therapy or the target lesion(s) within the field of local therapy have subsequently progressed in accordance with RECIST v1.1

  • Consent to using archival tumor tissues, if available

    • NOTE: Non-availability of tumor tissue does not exclude the subject.
  • Willingness to provide mandatory blood specimens for correlative research
  • Willingness to provide mandatory tissue specimens for correlative research for the first 10 patients per arm (Mayo Clinic Rochester and Mayo Clinic Arizona ONLY)
  • (ANC) >= 1.5 x 10\^9/L (1500/uL) without granulocyte colony-stimulating factor support (obtained =\< 28 days prior to randomization)
  • Lymphocyte count >= 0.5 x 10\^9/L (500/uL) (obtained =\< 28 days prior to randomization)
  • count >= 75 x 10\^9/L (75,000/uL) (obtained =\< 28 days prior to randomization)

  • >= 90 g/L (9 g/dL) (obtained =\< 28 days prior to randomization)

    • Subjects may be transfused to meet this criterion
  • (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) =\< 5 x (ULN) (obtained =\< 28 days prior to randomization)
  • Total =\< 3 x ULN (obtained =\< 28 days prior to randomization)
  • Serum albumin >= 30 g/L (3.0 g/dL) (obtained =\< 28 days prior to randomization)
  • For subjects not receiving therapeutic anticoagulation: (INR) or partial thromboplastin time (aPTT) =\< 1.5 × ULN (obtained =\< 28 days prior to randomization)
  • Serum creatinine =\< 2 x ULN or >= 30 mL/min (calculated using the Cockcroft-Gault formula) (obtained =\< 28 days prior to randomization)

  • Negative pregnancy test done =\< 14 days prior to randomization, for women of only

    • NOTE: If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  • Resolution of any acute, treatment-related toxicity from prior therapy to grade =\< 1 prior to randomization, with the exception of alopecia and peripheral sensory neuropathy.
  • Subjects of childbearing potential agree to use two forms of medically approved while taking the study drug and for at least 5 months after the last dose of atezolizumab or multi-kinase inhibitor. Subjects with partners of childbearing potential agree to use condoms, even after vasectomy, to avoid potential drug exposure to partner during study drug and for 5 months following the last dose of study drug
  • Ability to take oral medications

Exclusion criteria

Exclusion Criteria:

  • Known diagnosis of fibrolamellar carcinoma, sarcomatoid carcinoma or mixed hepatocellular cholangiocarcinoma

  • Prior multi-kinase inhibitor treatment for advanced disease (e.g., cabozantinib, lenvatinib, sorafenib, regorafenib)

    • NOTE: Use of multi-kinase inhibitor(s) for adjuvant or as part of loco-regional therapies is allowed as long as the therapy was completed >= 6 months prior to randomization

  • Any of the following prior therapies:

    • Major surgery =\< 4 weeks prior to randomization; Minor surgery =\< 7 days prior to randomization (e.g., simple excision, tooth extraction, insertion of central lines/Mediport). Subjects with complications from prior surgery are not eligible
    • Any anti-cancer agent =\< 2 weeks prior to randomization
    • Radiation therapy =\< 4 weeks (1 week for palliative radiation for bone and/or for pain control) or radionuclide treatment (e.g., I-131 or Y-90) =\< 6 weeks prior to randomization
  • Treatment with therapy =\< 28 days prior to randomization
  • Known brain or
  • Known co-infection of and . Subjects with a history of HCV infection but who are negative for HCV ribonucleic acid (RNA) by polymerase chain reaction (PCR) will be considered non-infected with HCV

  • Active or history of disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjogren syndrome, Guillain-Barre syndrome, or multiple sclerosis with the following exceptions:

    • Subjects with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study
    • Subjects with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study

    • Subjects with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., subjects with psoriatic arthritis are excluded) are eligible for the study provided all of the following conditions are met:

      • Rash must cover \< 10% of body surface area
      • Disease is well controlled at baseline and requires only low-potency topical
      • No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months

  • History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan

    • NOTE: History of radiation pneumonitis in the radiation field (fibrosis) is permitted
  • Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the subject at high risk from treatment complication
  • Treatment with a live, attenuated vaccine =\< 4 weeks prior to randomization, or anticipation of need for such a vaccine during atezolizumab treatment or =\< 5 months after the last dose of atezolizumab
  • History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
  • Known to Chinese hamster ovary cell products or to any component of the atezolizumab formulation
  • Subjects with untreated or incompletely treated esophageal/gastric varices with bleeding or high risk for bleeding. Subjects treated with adequate endoscopic therapy (according to local institutional standards) without any episodes of recurrent gastrointestinal bleeding requiring transfusion or hospitalization for > 28 days prior to randomization are eligible
  • Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 [IL-2]) =\< 4 weeks or 5 drug elimination half-lives (whichever is longer) prior to randomization

  • Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including , anti-PD-1, and anti-PD-L1 therapeutic antibodies

    • Note: Prior treatment with atezolizumab is permitted

  • Treatment with systemic medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF alpha agents) =\< 2 weeks prior to randomization, or anticipation of need for systemic immunosuppressive medication during study treatment, with the following exceptions:

    • Subjects who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible for the study
    • Subjects who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible
  • For subjects who are to receive cabozantinib: Treatment with strong inducers and/or strong inhibitors of =\< 14 days prior to randomization, including rifampin (and its analogues) or St. John's wort. See https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers for lists of known strong inhibitors and strong inducers of CYP3A4
  • Active tuberculosis

  • Other uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:

    • Cardiovascular disorders including:

      • Symptomatic congestive heart failure, unstable angina, or serious cardiac arrythmias
      • Uncontrolled hypertensions defined as sustained blood pressure (BP) > 150 mmHg systolic BP, or > 100 mmHg diastolic BP despite optimal antihypertensive treatment
      • Stroke (including ), myocardial infarction, or other ischemic event =\< 3 months prior to randomization.
      • Unstable arrythmia
      • Thromboembolic event =\< 3 months prior to randomization. Subjects with thromboses of portal/hepatic vasculature attributed to underlying liver disease and/or liver tumor are eligible.
    • Active bacterial infection requiring systemic treatment. Subjects on prophylactic antibiotics are eligible.
    • Known (HIV) infection or known acquired immunodeficiency syndrome (AIDS) related illness. Subjects with known HIV but without clinical evidence of an immunocompromised state and receiving anti-retroviral therapy are eligible
    • Prior allogenic stem cell or solid organ transplantation

    • Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)

      • Subjects with indwelling catheters (e.g., PleurX) are allowed.
    • Uncontrolled or symptomatic hypercalcemia (ionized calcium > 1.5 mmol/L, calcium > 12 mg/dL or corrected serum calcium > )

    • Uncontrolled tumor-related pain

      • Patients requiring pain medication must be on a stable regimen at the time of randomization
      • Symptomatic lesions (e.g., bone metastases or metastases causing nerve impingement) amenable to palliative radiotherapy should be treated prior to randomization. Patients should be recovered from the effects of radiation. There is no required minimum recovery period.
      • Asymptomatic metastatic lesions that would likely cause functional deficits or intractable pain with further growth (e.g., epidural metastasis that is not currently associated with spinal cord compression) should be considered for loco-regional therapy if appropriate prior to randomization
  • Other (ies) =\< 5 years prior to randomization except adequately treated non-melanotic skin cancer, carcinoma-in-situ of the cervix, localized prostate cancer, ductal carcinoma in situ or stage I uterine cancer
  • Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within at least 5 months after the last dose of study medication
  • Uncontrolled hepatic encephalopathy occurring =\< 6 weeks prior to randomization NOTE: Patients with =\< grade 2 encephalopathy =\< 6 weeks prior to randomization are eligible and supportive measures such as lactulose and antibiotics are allowed
Terms in these criteria, in plain language(31)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

Metastases

Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.

Line of therapy

A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.

“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.

ECOG performance status

A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.

0
Fully active, no restrictions.
1
Limited in strenuous activity, but walking and able to do light work, such as housework or office work.
2
Walking and able to look after yourself, but unable to work; up and about more than half of waking hours.
3
Able to look after yourself only in part; in bed or a chair more than half of waking hours.
4
Unable to look after yourself at all; in bed or a chair all day.

Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.

Child-Pugh class

A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.

Hepatitis B tests

Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.

Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.

Hepatitis C tests

Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.

After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.

RECIST

The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.

“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.

Absolute neutrophil count (ANC)

The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.

It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.

Platelets

Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.

Hemoglobin (Hb)

The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).

ALT and AST (liver enzymes)

Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.

Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.

ULN (upper limit of normal)

The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.

“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.

Bilirubin

A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.

Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.

INR, PT and aPTT (clotting tests)

Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.

Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.

Creatinine clearance (CrCl)

How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.

Childbearing potential

Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).

Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.

Clinically significant

Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.

Contraception

Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.

Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.

Investigational drug or device

A drug or device being studied in a clinical trial.

It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.

Leptomeningeal disease

Cancer that has spread to the leptomeninges, the thin layers covering the brain and spinal cord, and the fluid between them. It is not the same as brain metastases.

Criteria often treat it separately, and many studies leave it out even where treated brain metastases are allowed.

Autoimmune disease

A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.

Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.

Corticosteroids (steroids)

Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.

Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.

Hypersensitivity

An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.

PD-1, PD-L1 and checkpoint inhibitors

PD-1, PD-L1 and CTLA-4 are proteins that act as brakes on the immune system. Checkpoint inhibitors, such as pembrolizumab or nivolumab, block them so the immune system can attack a cancer.

PD-L1 can also be measured in a tumour sample. Some scores count stained tumour cells only (TPS); others also count certain immune cells (CPS). The study names the score and the minimum it uses.

Immunosuppression

A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.

Read whether the line is about a condition or about medicines, and which medicines and doses it means.

COPD

Chronic obstructive pulmonary disease: long-term lung disease that makes it hard to breathe out, including emphysema and chronic bronchitis.

CYP3A (CYP3A4) inhibitors and inducers

CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.

Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.

TIA (transient ischaemic attack)

A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.

Stroke symptoms need emergency care at once, even if they go away.

HIV

The human immunodeficiency virus, which weakens the immune system.

Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.

Cancer (malignancy)

Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.

Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.

05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
122 participants (estimated)

Study arms

  • Experimental
    Arm A (atezolizumab, cabozantinib or lenvatinib)

    Patients receive atezolizumab IV over 30-60 minutes on day 1 and cabozantinib PO QD or lenvatinib PO QD on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

    Biological: Atezolizumab · Drug: Cabozantinib · Drug: Lenvatinib

  • Active comparator
    Arm B (cabozantinib or lenvatinib)

    Patients receive cabozantinib PO QD or lenvatinib PO QD on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

    Drug: Cabozantinib · Drug: Lenvatinib

Interventions

  • BiologicalAtezolizumab

    Given IV

    Also known as: MPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A, MPDL328OA, RG7446, RO5541267, Tecentriq

  • DrugCabozantinib

    Given PO

  • DrugLenvatinib

    Given PO

    Also known as: E7080, ER-203492-00, Multi-Kinase Inhibitor E7080

06

What researchers measure

Primary outcomes

  1. Overall survival (OS)

    The final analysis for OS will be conducted when 84 OS events are observed, approximately 36 months after first subject in and will be evaluated with a one-sided p-value from stratified log-rank test.

    Time frame: From randomization to death from any cause, assessed up to 3 years

  2. Progression-free survival (PFS)

    PFS analysis will be conducted when 89 PFS events are observed. The one-sided p-value from stratified log-rank test will be used for decision making.

    Time frame: From randomization to first documentation of disease progression (per Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) or death, assessed up to 2 years

Secondary outcomes

  1. Objective response rate (ORR)

    Objective response is defined as either a complete response (CR) or partial response (PR) (as defined by the RECIST 1.1). ORR will be calculated by the number of subjects experience objective response divided by the number of evaluable subjects in each arm. Confidence intervals for the ORR will be calculated using a normal approximation and the corresponding 95% confidence interval will be reported.

    Time frame: Up to 2 years

  2. Duration of response

    For subjects who experience a CR or PR, duration of response is defined as the time from the date of first response (CR or PR) to progression or death, whichever is earliest. Median duration for each arm and corresponding 95% confidence interval, calculated using Kaplan-Meier method and Brookmeyer-Crowley, will be reported.

    Time frame: Up to 2 years

  3. Incidence of adverse events (AEs)

    Common Terminology Criteria for Adverse Events (CTCAE) AEs will be recorded for each subject. The overall adverse event rates for grade 3 or higher AEs will be reported by arm.

    Time frame: Up to 30 days after last dose

07

Study locations

10 of 16 sites recruiting
08

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reachedSimilar studies: half by the dot; the band is the middle halfHalf of similar studies reached it by the dot; the band is the middle half, from a quarter to three quarters

Ran from May 2022 to primary completion in Jun 2026, 49 months.

Of 348 non-industry phase 2 interventional studies under Carcinoma, Hepatocellular, half reached primary completion within 47 months of starting (the median), counting those still running; a quarter within 33 and three quarters within 78. This study's 49 months is close to that.

Counting every sponsor, half of 428 studies reached it within 43 months; a quarter within 30 and three quarters within 71.

How these figures are worked out, and which studies are left out of them.

Registered
Dec 8, 2021
First posted
Dec 23, 2021
StartActual
May 27, 2022
Primary completionActual
Jun 30, 2026
CompletionEst.
Dec 31, 2026
Last update
Aug 4, 2026
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Aug 4, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
09

Registry details

Key details

Study ID
NCT05168163
Lead sponsor
Academic and Community Cancer Research United
Collaborators
National Cancer Institute (NCI), Genentech, Inc.
Responsible party
Sponsor
First posted
Dec 23, 2021
Start date
May 27, 2022
Primary completion
Jun 30, 2026
Completion
Dec 31, 2026 (estimated)
Last update
Aug 4, 2026

Study contacts

Wen Wee Ma
principal investigator · Academic and Community Cancer Research United

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Studies of the drug tested here: Atezolizumab

Other studies in this condition

Carcinoma, Hepatocellular →

Other studies from this sponsor

Academic and Community Cancer Research United

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