Hepatocellular CarcinomaPhase 1CLeARNCT07365839
Cemiplimab +/- Fianlimab Post Y90 Radioembolization in Patients With Hepatocellular Carcinoma
A Phase 1 study testing Arm 1 cemiplimab and Arm 2 cemiplimab and fianlimab in people with Hepatocellular Carcinoma, run by Virginia Commonwealth University.
Trial summary
Randomized, 2-arm, non-comparative, pilot study assessing the efficacy of cemiplimab with or without fianlimab after treatment with yttrium-90 (Y90). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- Arm 1 cemiplimab and Arm 2 cemiplimab and fianlimab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 1 Oct 2026to 28 May 2035
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of hepatocellular carcinoma (HCC) in the liver by radiographic imaging or histology
- Eligible for yttrium-90 (Y90) treatment by the following definition:
- Patients must have lung dose threshold for Y90 glass microspheres of 30 Gy (≤ 30 Gy per treatment for glass) and an estimated future liver remnant volume (FLRV) ≥ 30% of whole liver volume
- Age ≥18 years
- Disease in the liver measurable by modified Response Evaluation Criteria in Solid Tumors (mRECIST)
- Child Pugh Scale Score A-B7
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- Not eligible for (according to the practice of the treating institution) or declined the following treatments:
- surgical resection
- immediate liver transplantation
- thermal ablation
- Eastern Cooperative Oncology Group (ECOG) performance status ≤2
- Troponin (TnT and TnI) ≤1 × upper limit of normal (ULN) at baseline Note: Patients with TnT or TnI levels between >1 to 2 × ULN are permitted if repeat levels within 24 hours are ≤1 × ULN. If TnT or TnI levels are >1 to 2 × ULN within 24 hours, the subject may undergo a cardiac evaluation and be considered for treatment by the investigator based on the medical judgement in the patient's best interest.
- Alkaline phosphatase ≤5 × ULN
- Aspartate aminotransferase (AST) ≤5 × ULN
- Alanine transaminase (ALT) ≤5 × ULN
- Creatinine clearance >30 mL/min (actual or calculated per the Cockcroft-Gault formula)
- Bilirubin ≤2 milligram/ deciliter (mg/dL) Exception: If a patient has documented Gilbert's syndrome and a total bilirubin is ≥2 mg/dL, the total bilirubin requirement may be waived provided the direct bilirubin is within normal limits (WNL)
- Patients with known Human immunodeficiency virus (HIV) infection are eligible if the following conditions are met:
- the HIV is well controlled with no AIDS-related complications
- undetectable viral load
- Cluster of Differentiation 4 (CD4)+ T-lymphocyte count(T-cell) above 350 cells/microliters (μL) Note: HIV testing is not required for study participation.
- Patients with known active hepatitis B virus (HBV) infection are eligible if the following conditions are met:
- serum HBV Deoxyribonucleic Acid (DNA) polymerase chain reaction ( PCR)below the limit of detection
- receiving anti-HBV treatment Note: HBV testing for diagnosis is not required for study entry. Determination of known active HBV infection is based on medical history.
- Patients with known chronic hepatitis C virus (HCV) infection are eligible if they have undetectable HCV RNA by PCR Note: HCV testing for diagnosis is not required for study entry. Determination of known chronic HCV infection is based on medical history. Receipt of anti-HCV medication has no bearing on study eligibility.
- Patients with HIV or hepatitis must have established longitudinal care with a qualified specialist (eg, infectious disease or hepatologist).
- Note: at the time of enrollment, the specialist providing longitudinal care must be documented in the source medical record.
- Women of childbearing potential (WOCBP) must have a negative serum beta-Human Chorionic Gonadotropin (hCG) at screening WOCBP are defined as women who are fertile following menarche until becoming postmenopausal, unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy.
- A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high Follicle-Stimulating Hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient to determine the occurrence of a postmenopausal state. The above definitions are according to the Clinical Trials Facilitation Group (CTFG) guidance20.
- WOCBP are required to practice highly effective contraception during the entire trial and for at least 6 months after the last dose of study treatment. Highly effective contraceptive measures include the following:
- Stable use of combined (estrogen and progestogen containing) hormonal contraception or progestogen-only hormonal contraception (oral, injectable, or implantable) associated with inhibition of ovulation initiated 8 weeks before the screening serum beta-hCG test
- Intrauterine device (IUD); intrauterine hormone-releasing system (IUS)
- Vasectomized partner, provided that the male vasectomized partner is the sole male sexual partner of the WOCBP study participant and that the vasectomized partner has obtained medical assessment of surgical success for the procedure
- Sexual abstinence, defined as refraining from heterosexual intercourse during the entire period of risk associated with the study drugs, if evaluated by the treating investigator to be reliable in relation to the duration of required contraception (up to 18 months) and the preferred and usual lifestyle of the participant.
- Note: period abstinence (calendar, symptothermal, post-ovulation methods), withdrawal, spermicides only, and lactational amenorrhea method are not acceptable methods of contraception.
- WOCBP must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the entire trial and for at least 6 months after the last dose of study treatment
- Male study participants with WOCBP partners are required to use condoms during the entire trial and for at least 6 months after the last dose of study treatment unless they are vasectomized or practice sexual abstinence.
- Vasectomized study participants must have received medical assessment of surgical success for the procedure.
- Sexual abstinence, defined as refraining from heterosexual intercourse during the entire period of risk associated with the study drugs, must be evaluated by the treating investigator to be reliable in relation to the duration of required contraception (up to 18 months) and the preferred and usual lifestyle of the participant.
- Male study participants must agree not to donate sperm during the entire trial and for at least 6 months after the last dose of study treatment
Who cannot join
- Any history of invasive malignancy within the past 3 years, except for the following:
- adequately treated basal cell or squamous cell skin cancer, localized prostate cancer, breast ductal carcinoma in situ, low-grade endometrial carcinoma, or in situ cervical cancer,
- localized prostate cancer under active surveillance or gonadotropin-releasing hormone (GNRH) therapy
- treating physician determines previous cancer has been adequately treated with high probability for cure (as documented in medical record)
- Presence of extrahepatic disease Note: non measurable (<1 centimeter (cm)) lesions outside the liver are acceptable if they do not represent a deterrent for Y90 treatment per the standards of the treating institution
- Receipt of more than 1 prior embolization (TACE or Y90) treatment/procedure
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- Portal vein thrombosis (PVT) Vp3 or Vp4
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (except viral hepatitis), symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or myocarditis
- Current enrollment in any other investigational therapeutic drug study
- Currently breastfeeding
- Recipient of an organ transplant, including bone marrow allogeneic transplant
- Previous systemic therapy for HCC
- Ongoing or recent (within 2 years) autoimmune disorder except for the following:
- Vitiligo
- Alopecia
- Hashimoto's thyroiditis
- Celiac disease controlled by diet
- Chronic skin conditions that do not require systemic therapy
- Childhood asthma that has resolved
- Residual hypothyroidism that requires only hormone replacement
- Use of immunosuppressive medication within 14 days before the first dose of study treatment, except the following:
- include topical, inhaled, local injection or intranasal steroids
- systemic steroids at doses of ≤10 mg/day of prednisone (equivalent)
- steroids for premedication
- TnT or troponin I TnI ≥ 2 × ULN at baseline
- History or current evidence of significant (CTCAE grade ≥2) local or systemic infection (eg, cellulitis, pneumonia, septicemia) requiring systemic antibiotic treatment within 2 weeks before the first dose of study treatment
- Active infection requiring treatment (except HIV/hepatitis as noted in inclusion criteria)
- Diagnosis of immunodeficiency that is related to, or results in, chronic infection (except HIV/hepatitis as noted in inclusion criteria) or is related to organ or allogeneic bone marrow transplant
- Known hypersensitivity to the active substances or to any of the excipient
- Received a live vaccine within 30 days before the planned start of study medication. Note that this applies to live or live attenuated vaccination with replicating potential
- Prior history of interstitial lung disease or pneumonitis
About this study
Official title: CLeAR: Pilot Study to Evaluate the Efficacy of Cemiplimab (PD-1 Inhibition) With or Without Fianlimab (LAG-3 Inhibition) After Y90 Radioembolization in Patients With Hepatocellular Carcinoma
Randomized, 2-arm, non-comparative, pilot study assessing the efficacy of cemiplimab with or without fianlimab after treatment with yttrium-90 (Y90).
Read the detailed description
At 2-8 weeks after yttrium-90 (Y90) radioembolization, patients will be randomized to receive treatment with cemiplimab or with a fixed-dose combination of cemiplimab and fianlimab. If Y90 is administered in 2 treatments, the first dose of the study treatment must be given no more than 12 weeks after first Y90 treatment and at least 2 weeks after the second treatment. Patients will receive the assigned study treatment once per 3-week cycle and will continue treatment for up to 17 cycles (approximately 1 year) or until disease progression or intolerance.
- Conditions
- Hepatocellular Carcinoma
- Being tested
- Arm 1 cemiplimab, Arm 2 cemiplimab and fianlimab
- Keywords
- Hepatocellular Carcinoma
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Arm 1 cemiplimabDrug
Also called Libtayo, Anti-PD-1 antibody
Cemiplimab 350mg IV every 3 weeks up to 1 year.
Arm 2 cemiplimab and fianlimabDrug
Also called Libtayo, Anti-PD-1 antibody & Anti-LAG-3 antibody
Cemiplimab 350mg IV and fianlimab 1600mg every 3 weeks up to 1 year
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 Treatment with cemiplimab | Experimental | 350 mg cemiplimab intravenous (IV) every 3 weeks Receives: Drug: Arm 1 cemiplimab |
| Arm 2 Treatment with | Experimental | 350 mg cemiplimab intravenous (IV) + 1600 mg fianlimab intravenous (IV) every 3 weeks Receives: Drug: Arm 2 cemiplimab and fianlimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assess the efficacy of cemiplimab with or without fianlimab as measured by progression-free survival (PFS)
Progression-free survival, defined as the number of days from the start date of Y90 treatment (administered two times) to the date of progression, relapse, or death.
Measured: Baseline, 6, 12, and 18 months, then every 6 months until off study up to 5 years
Secondary outcomes (5)
Evaluate the safety and toxicity profile of cemiplimab with or without fianlimab based on the number of patients experiencing grade greater than grade 3 treatment-related adverse events (TRAE).
Incidence of treatment-related grade ≥3 adverse events as defined in the National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE v5.0). Adverse event (AE) means any untoward medical occurrence associated with the use of a drug in humans.
Measured: Baseline through 90 days following end of treatment (EOT) up to 5 years
Assess the objective response rate (ORR) for patients receiving cemiplimab with or without fianlimab.
The percentage of patients who have a complete response (CR) and a partial response (PR) as measured by Modified (Response Evaluation Criteria in Solid Tumors) (mRECIST). mRECIST is a method to adapt the RECIST 1.1 criteria to measure HCC specifically. mRECIST only takes the viable tumor into account, which allows necrosis of the tumor to not be mistaken for progression.
Measured: 6, 12, and 18 months
Assess the progression free survival (PFS) rate for patients receiving cemiplimab with or without fianlimab
Using response from mRECIST criteria to determine date of progression for calculation of PFS
Measured: 6, 12, and 18 months, then every 6 months until off study up to 5 years
Assess the median overall survival (OS) for patients receiving cemiplimab with or without fianlimab.
Overall survival, defined as time from the date of Y90 treatment to the date of death by any cause, measured by the number of participants alive through study completion.
Measured: 6, 12 and 18 months then every 6 months until off study up to 5 years
Assess the overall survival (OS) rate for patients receiving cemiplimab with or without fianlimab.
Overall survival, defined as time from the date of Y90 treatment to the date of death by any cause
Measured: 6, 12 and 18 months, then every 6 months until off study up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2026
- Study start1 Oct 2026 (estimated)
- Primary completion28 May 2035 (estimated)
- Study completion28 May 2035 (estimated)
Why it stopped: The study was withdrawn because the pharmaceutical company decided not to pursue this combination of drugs following negative data in another indication.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by Virginia Commonwealth UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Virginia Commonwealth University
- Sponsor type
- University, hospital or other
- Collaborators
- Regeneron Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Emily Kinsey, MD, Principal investigator, Virginia Commonwealth University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07365839
- Sponsor's protocol ID
- MCC-24-21103
- Acronym
- CLeAR
- Status last verified
- Sep 2026
- First submitted
- 16 Jan 2026
- Last updated
- 14 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: There are no plans to share individual participant data (IPD) at this time.
Study at a glance
From the registry record, last updated by the sponsor on 14 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- CLeAR: Pilot Study to Evaluate the Efficacy of Cemiplimab (PD-1 Inhibition) With or Without Fianlimab (LAG-3 Inhibition) After Y90 Radioembolization in Patients With Hepatocellular Carcinoma
- ClinicalTrials.gov ID
- NCT07365839
- Acronym / sponsor ID
- CLeAR / MCC-24-21103
- Conditions
- Hepatocellular Carcinoma
- Keywords
- Hepatocellular Carcinoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: The study was withdrawn because the pharmaceutical company decided not to pursue this combination of drugs following negative data in another indication.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Virginia Commonwealth UniversityUniversity, hospital or other
- Collaborators
- Regeneron Pharmaceuticals
- Study start
- 1 Oct 2026 (estimated)
- Primary completion
- 28 May 2035 (estimated)
- Study completion
- 28 May 2035 (estimated)
- First posted
- 26 Jan 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Randomized, 2-arm, non-comparative, pilot study assessing the efficacy of cemiplimab with or without fianlimab after treatment with yttrium-90 (Y90).
Detailed description
At 2-8 weeks after yttrium-90 (Y90) radioembolization, patients will be randomized to receive treatment with cemiplimab or with a fixed-dose combination of cemiplimab and fianlimab. If Y90 is administered in 2 treatments, the first dose of the study treatment must be given no more than 12 weeks after first Y90 treatment and at least 2 weeks after the second treatment. Patients will receive the assigned study treatment once per 3-week cycle and will continue treatment for up to 17 cycles (approximately 1 year) or until disease progression or intolerance.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1 Treatment with cemiplimab | Experimental | Drug: Arm 1 cemiplimab350 mg cemiplimab intravenous (IV) every 3 weeks |
| Arm 2 Treatment with | Experimental | Drug: Arm 2 cemiplimab and fianlimab350 mg cemiplimab intravenous (IV) + 1600 mg fianlimab intravenous (IV) every 3 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (40 listed)
- Diagnosis of hepatocellular carcinoma (HCC) in the liver by radiographic imaging or histology
- Eligible for yttrium-90 (Y90) treatment by the following definition:
- Patients must have lung dose threshold for Y90 glass microspheres of 30 Gy (≤ 30 Gy per treatment for glass) and an estimated future liver remnant volume (FLRV) ≥ 30% of whole liver volume
- Age ≥18 years
- Disease in the liver measurable by modified Response Evaluation Criteria in Solid Tumors (mRECIST)
Key exclusion criteria (31 listed)
- Any history of invasive malignancy within the past 3 years, except for the following:
- Presence of extrahepatic disease Note: non measurable (<1 centimeter (cm)) lesions outside the liver are acceptable if they do not represent a deterrent for Y90 treatment per the standards of the treating institution
- Receipt of more than 1 prior embolization (TACE or Y90) treatment/procedure
- Portal vein thrombosis (PVT) Vp3 or Vp4
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (except viral hepatitis), symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or myocarditis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Arm 1 cemiplimabAlso: Libtayo, Anti-PD-1 antibodyCemiplimab 350mg IV every 3 weeks up to 1 year. | Drug | Arm 1 Treatment with cemiplimab |
| Arm 2 cemiplimab and fianlimabAlso: Libtayo, Anti-PD-1 antibody & Anti-LAG-3 antibodyCemiplimab 350mg IV and fianlimab 1600mg every 3 weeks up to 1 year | Drug | Arm 2 Treatment with |
Primary outcome
Assess the efficacy of cemiplimab with or without fianlimab as measured by progression-free survival (PFS)
Time frame: Baseline, 6, 12, and 18 months, then every 6 months until off study up to 5 years
Progression-free survival, defined as the number of days from the start date of Y90 treatment (administered two times) to the date of progression, relapse, or death.
5 secondary outcomes
Evaluate the safety and toxicity profile of cemiplimab with or without fianlimab based on the number of patients experiencing grade greater than grade 3 treatment-related adverse events (TRAE).
Time frame: Baseline through 90 days following end of treatment (EOT) up to 5 years
Assess the objective response rate (ORR) for patients receiving cemiplimab with or without fianlimab.
Time frame: 6, 12, and 18 months
Assess the progression free survival (PFS) rate for patients receiving cemiplimab with or without fianlimab
Time frame: 6, 12, and 18 months, then every 6 months until off study up to 5 years
Assess the median overall survival (OS) for patients receiving cemiplimab with or without fianlimab.
Time frame: 6, 12 and 18 months then every 6 months until off study up to 5 years
Assess the overall survival (OS) rate for patients receiving cemiplimab with or without fianlimab.
Time frame: 6, 12 and 18 months, then every 6 months until off study up to 5 years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Sep 2026.
- Individual participant dataSharing planned: No. There are no plans to share individual participant data (IPD) at this time.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Emily Kinsey, MD principal investigator
Virginia Commonwealth University
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Arm 1 cemiplimab and Arm 2 cemiplimab and fianlimab in people with Hepatocellular Carcinoma, run by Virginia Commonwealth University.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 40 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 14 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assess the efficacy of cemiplimab with or without fianlimab as measured by progression-free survival (PFS) (time frame: Baseline, 6, 12, and 18 months, then every 6 months until off study up to 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Sep 2026.