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Hepatocellular CarcinomaPhase 1/2NCT06294548

A Study of Valemetostat Tosylate (DS-3201b) With Atezolizumab and Bevacizumab in HCC

A Phase 1/2 study testing Valemetostat, Atezolizumab and Bevacizumab in people with Hepatocellular Carcinoma, run by University of Alabama at Birmingham at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

This is a phase Ib/II, dose escalation and dose expansion study of valemetostat (DS-3201) with atezolizumab and bevacizumab in patients advanced Hepatocellular carcinoma (HCC) who did not receive prior systemic therapy for advanced HCC. 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?
Valemetostat, Atezolizumab and Bevacizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
45 participants
Where
1 siteUnited States
Study dates
29 Jul 2025to 28 Aug 2028
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

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

  • Subjects must meet all the following criteria to be eligible for enrollment into the study:
  • Sign and date the informed consent form (ICF), prior to the start of any study-specific qualification procedures.
  • Subjects ≥18 years of age or the minimum legal adult age (whichever is greater) at the time the ICF is signed
  • HCC diagnosis confirmed by histology/cytology or clinically by American Association for Study of Liver Diseases (AASLD) 36 criteria in cirrhotic patients.
  • At least one measurable untreated lesion per RECIST v1.1 (see Section 12). Patients who received prior liver directed therapy (ie., Trans arterial chemoembolization [TACE], Y-90, liver directed radiation etc.) are eligible provided the target lesion(s) have not been previously treated with liver directed therapy or the target lesion(s) within the field of local therapy have subsequently progressed in accordance with RECIST v1.1 (See Section 12)
  • Locally advanced, metastatic, or unresectable disease.
Show all 37Show fewer
  • No prior systemic therapy for advanced HCC.
  • Child Pugh Class A.
  • Barcelona Clinic Liver Cancer (BCLC) Stage B (not amenable to liver directed therapy) or Stage C.
  • ECOG Performance Status (PS) 0 or 1.
  • The following laboratory values obtained ≤ 28 days prior to registration. Local laboratory data must meet the following criteria at both Screening and prior to dosing on the planned Cycle 1 Day 1 visit to confirm relatively preserved organ function:
  • Absolute neutrophil count (ANC) ≥1500/mm3
  • Platelet count 100,000/mm3 (platelet transfusion is not allowed within 14 days prior to screening assessment).
  • Hemoglobin (Hgb) 9.0 g/dL (red blood cell transfusion is not allowed within 14 days prior to screening assessment).
  • Total bilirubin (TBIL) ≤1.5 x ULN.
  • ALT and AST ≤3 x ULN
  • For patients not receiving therapeutic anticoagulation INR or aPTT ≤2 x ULN
  • Creatinine clearance ≥40 mL/min (measured by the Cockcroft-Gault equation)
  • If the subject is a female of childbearing potential, she must have a negative serum pregnancy test at Screening and must be willing to use highly effective birth control, as detailed in Section 4.4, upon enrollment, during the Treatment Period, and for 6 months, following the last dose of study drug. A female is considered of childbearing potential following menarche and until becoming postmenopausal (no menstrual period for a minimum of 12 months) unless permanently sterile (undergone a hysterectomy, bilateral salpingectomy or bilateral oophorectomy) with surgery at least 1 month before the first dose of study drug or confirmed by follicle stimulating hormone (FSH) test >40 mIU/mL and estradiol <40 pg/mL (<140 pmol/L).
  • If male with partner of childbearing potential, the subject must be surgically sterile or willing to use highly effective birth control (Section 4.4) upon enrollment, during the Treatment Period, and for 6 months following the last dose of study drug.
  • Female subjects must not donate, or retrieve for their own use, ova from the time of screening and throughout the study treatment period, and for at least 6months after the final study drug administration.
  • Male subjects must not freeze or donate sperm starting at Screening and throughout the study period, and for at least 6 months after the final study drug administration.
  • Provide informed written consent ≤28 days prior to registration.
  • 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), participants must be willing to return to the consenting institution for follow-up.
  • Willing to provide mandatory blood specimens for correlative research purposes (see Section 10).
  • Unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to NCI-CTCAE v 5.0, Grade ≤1 or Baseline.
  • Note: Subjects may be enrolled with chronic, stable Grade 2 toxicities (defined as no worsening to > Grade 2 for at least 3 months prior to enrollment and managed with standard of care treatment), which the Investigator deems related to previous anticancer therapy, composed of the following:
  • Chemotherapy-induced neuropathy.
  • Fatigue.
  • Residual toxicities from prior immunotherapy treatment: Grade 1 or 2 endocrinopathies, which may include the following:
  • Hypothyroidism/ hyperthyroidism.
  • Type I diabetes.
  • Hyperglycemia.
  • Adrenal insufficiency.
  • Adrenalitis.
  • Skin hypopigmentation (vitiligo).

Who cannot join

  • Subjects who meet any of the following criteria will be disqualified from entering the study:
  • Any of the following because this study involves an investigational agent whose genotoxic, mutagenic, and teratogenic effects on the developing fetus and newborn are unknown:
  • Pregnant persons
  • Nursing persons
  • Persons of childbearing potential who are unwilling to employ adequate contraception
  • Liver directed therapy (Trans arterial chemoembolization [TACE], Y-90, liver directed radiation, etc.) ≤ 28 days prior to registration.
Show all 54Show fewer
  • Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.
  • Uncontrolled or significant cardiovascular disease, including the following:
  • Evidence of prolongation of QT/QTc interval (eg, repeated episodes of QT corrected for heart rate using Fridericia's method [QTcF] >470 ms) (average of triplicate determinations)
  • Myocardial infarction within 6 months prior to Screening
  • Uncontrolled angina pectoris within 6 months prior to Screening
  • New York Heart Association (NYHA) Class 3 or 4 congestive heart failure
  • Inadequately controlled hypertension (defined as systolic blood pressure ≥150 mmHg and/or diastolic blood pressure >100 mmHg, based on average ≥3 blood pressure readings on ≥2 sessions. Anti-hypertensive therapy to achieve these parameters is allowed.
  • Prior malignancy active within the previous 3 years except for locally curable cancer that is currently considered as cured, such as cutaneous basal or squamous cell carcinoma, superficial bladder cancer, or cervical carcinoma in situ, or an incidental histological finding of prostate cancer.
  • History of treatment with other EZH inhibitors
  • Current use of moderate or strong cytochrome P450 (CYP)3A inducers, and strong CYP3A and/or P-gp inhibitors in dose escalation phase (See Table 11).
  • Immunocompromised patients and patients known to be Human immunodeficiency virus (HIV) positive and currently receiving antiretroviral therapy or known acquired immunodeficiency syndrome.
  • Regarding hepatitis B, patients must meet the following criteria to be eligible:
  • Patients with Hepatitis B (positive HBs antigen test) have an HBV-DNA Viral Load <2000 IU/mL off treatment or on oral antiviral therapy for at least 4 weeks and during the participation in the study.
  • For patients at high-risk of Hepatitis B reactivation: Patients with contact to the Hepatitis B virus (positive HBc antibody) that did not develop immunity (negative HBs antibody) must have an HBV-DNA Viral Load <100 IU/mL on oral antiviral therapy for at least 4 weeks and during the participation in the study.
  • Patient has active Hepatitis C. Active Hepatitis C is defined by a positive Hep C Ab result and quantitative HCV RNA results greater than the lower limits of detection of the assay.
  • Evidence of ongoing uncontrolled systemic bacterial, fungal, or viral infection requiring treatment with intravenous antibiotics, antivirals, or antifungals. Note: Subjects with localized fungal infections of skin or nails are eligible.
  • A medical history or complication considered inappropriate for participation in the study, or a serious physical or psychiatric disease, the risk of which may be increased by participation in the study in the investigator's opinion.
  • Psychological, social, familial, or geographical factors or substance abuse that would prevent regular follow-up to be compliant with the protocol.
  • History of hemoptysis (≥2.5 mL of bright red blood per episode) within 1 month prior to initiation of study treatment
  • Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
  • Current or recent (within 10 days of first dose of study treatment) use of aspirin (> 325 mg/day) or treatment with dipyramidole, ticlopidine, clopidogrel, and cilostazol.
  • Current or recent (within 10 days prior to study treatment start) use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic (as opposed to prophylactic) purpose. Prophylactic anticoagulation for the patency of venous access devices is allowed provided the activity of the agent results in an INR < 1.5 x ULN and aPTT is within normal limits within 14 days prior to initiation of study treatment. Prophylactic use of low molecular-weight heparin (i.e., enoxaparin 40 mg/day) is allowed.
  • Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 3 days prior to the first dose of bevacizumab.
  • History of abdominal or tracheoesophageal fistula, gastrointestinal (GI) perforation, or intra-abdominal abscess within 6 months prior to initiation of study treatment
  • History of intestinal obstruction and/or clinical signs or symptoms of GI obstruction including sub-occlusive disease related to the underlying disease or requirement for routine parenteral hydration, parenteral nutrition, or tube feeding within 6 months prior to initiation of study treatment. Patients with signs/symptoms of sub-/occlusive syndrome/intestinal obstruction at time of initial diagnosis may be enrolled if they had received definitive (surgical) treatment for symptom resolution.
  • Evidence of abdominal free air that is not explained by paracentesis or recent surgical procedure.
  • Serious, non-healing or dehiscing wound, active ulcer, or untreated bone fracture
  • Metastatic disease that involves major airways or blood vessels, or centrally located mediastinal tumor masses (< 30 mm from the carina) of large volume Patients with vascular invasion of the portal or hepatic veins may be enrolled.
  • History of intra-abdominal inflammatory process within 6 months prior to initiation of study treatment, including but not limited to peptic ulcer disease, diverticulitis, or colitis
  • Radiotherapy within 28 days and abdominal/ pelvic radiotherapy within 60 days prior to initiation of study treatment, except palliative radiotherapy to bone lesions within 7 days prior to initiation of study treatment
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to initiation of study treatment, or abdominal surgery, abdominal interventions or significant abdominal traumatic injury within 60 days prior to initiation of study treatment or anticipation of need for major surgical procedure during the course of the study or non-recovery from side effects of any such procedure
  • Chronic daily treatment with a non-steroidal anti-inflammatory drug (NSAID). Occasional use of NSAIDs for the symptomatic relief of medical conditions such as headache or fever is allowed.
  • Known fibrolamellar carcinoma (FLC), sarcomatoid HCC, or combined hepatocellular-cholangiocarcinoma (cHCC-CC)
  • Patients with untreated or incompletely treated varices with bleeding or high-risk for bleeding. Patients must undergo an esophagogastroduodenoscopy (EGD), and all size of varices (small to large) must be assessed and treated per local standard of care prior to enrollment. Patients who have undergone an EGD within 6 months of prior to initiation of study treatment do not need to repeat the procedure.
  • History of allogenic organ transplantation.
  • Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], 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:
  • Patients with vitiligo or alopecia
  • Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
  • Any chronic skin condition that does not require systemic therapy
  • Patients without active disease in the last 5 years may be included but only after consultation with the study physician
  • Patients with celiac disease controlled by diet alone
  • History of leptomeningeal carcinomatosis or intracranial metastases
  • Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
  • Current or prior use of immunosuppressive medication ≤ 14 days prior to registration. The following are exceptions to this criterion:
  • Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)
  • Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
  • Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
  • Receipt of live attenuated vaccine ≤30 days prior to registration. Note: Patients, if enrolled, should not receive live vaccine whilst on study treatment and up to 30 days after the last dose of study treatment.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Margaret Thomas, MPH contact

205-895-1802

margaretannthomas@uabmc.edu

United States1 site, 1 recruiting

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35294

    Margaret Thomas, MPH, margaretannthomas@uabmc.edu

    Mehmet S Akce, MD

    Recruiting

Other trials in United States

About this study

Official title: A Phase Ib/II, Dose Escalation and Dose Expansion Study of Valemetostat Tosylate (DS-3201b) With Atezolizumab and Bevacizumab in Advanced Hepatocellular Carcinoma (HCC)

This is a phase Ib/II, dose escalation and dose expansion study of valemetostat (DS-3201) with atezolizumab and bevacizumab in patients advanced Hepatocellular carcinoma (HCC) who did not receive prior systemic therapy for advanced HCC.

Read the detailed description

Patients will be started on valemetostat (DS-3201) with atezolizumab and bevacizumab, restaging scans will be performed every 9 weeks. The treatment will be continued until progressive disease (PD), unacceptable toxicity or consent withdrawal. Paired research biopsies will be performed.

This study will enroll up to approximately 45-patients at UAB. It is estimated 2 patients will be enrolled per month over up to 36 months period.

Patients will receive valemetostat (DS-3201) orally daily at their assigned dose level, plus atezolizumab 1200 mg intravenously (IV) on day 1, and bevacizumab 15 mg/kg IV on day 1 of each cycle. Each cycle is 21 days. Atezolizumab and bevacizumab will be administered based on institutional guidelines and practice at the FDA approved dosages and intervals for advanced HCC. Valemetostat should be taken immediately prior to the start of atezolizumab and bevacizumab infusion on day 1 of each cycle.

Being tested
Valemetostat, Atezolizumab, Bevacizumab
Medical subject headings
Carcinoma, Hepatocellular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ValemetostatDrug

    Also called Valemetostat tosylate, Valemetostat (DS-3201)

    Valemetostat is an inhibitor of the enzymes enhancer of zeste homolog 1 (EZH1) and enhancer of zeste homolog 2 (EZH2).

  • AtezolizumabDrug

    Atezolizumab is commercially available. Atezolizumab combined with bevacizumab is approved for frontline treatment of advanced HCC based on IMbrave150 clinical trial. It will be administered as per the package insert and institutional standards.

  • BevacizumabDrug

    Bevacizumab is commercially available. Bevacizumab combined with atezolizumab is approved for frontline treatment of advanced HCC based on IMbrave150 clinical trial. It will be administered as per the package insert and institutional standards.

Study groups in NCT06294548
Study groupRoleWhat they receive
Phase 1b: Valemetostat + Atezolizumab 1200 mg + Bevacizumab 15 mg/kgExperimentalIn Phase 1b patients will receive valemetostat (DS-3201) orally daily at their assigned dose level, plus atezolizumab 1200 mg intravenously (IV) on day 1, and bevacizumab 15 mg/kg IV on day 1 of each cycle. During Phase 1b, a 3+3 dose escalation design will be utilized to define the maximum tolerated dose (MTD) or recommended phase II dose (RP2D) with starting dose of valemetostat 150mg by mouth daily.
Receives: Drug: Valemetostat; Drug: Atezolizumab; Drug: Bevacizumab
Phase II: Valemetostat + Atezolizumab 1200 mg + Bevacizumab 15 mg/kgExperimentalDuring Phase II, study participants will receive valemetostat (DS-3201) orally daily at MTD/RP2D, plus atezolizumab 1200 mg intravenously (IV) on day 1, and bevacizumab 15 mg/kg IV on day 1 of each cycle.
Receives: Drug: Valemetostat; Drug: Atezolizumab; Drug: Bevacizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase 1b

    Evaluate the safety, tolerability, and MTD/RP2D of valemetostat when administered with atezolizumab and bevacizumab in advanced HCC (phase 1b).

    Measured: Baseline up to 36 months

  2. Phase II

    Estimate the objective response rate (ORR) by RECIST version 1.1. per investigator assessment for valemetostat when administered with atezolizumab and bevacizumab at RP2D in advanced HCC (phase II).

    Measured: Baseline up to 36 months

Secondary outcomes (5)

  1. Safety and pharmacokinetics (PK)

    Evaluate the safety and pharmacokinetic (PK) profile of valemetostat in combination with atezolizumab and bevacizumab.

    Measured: Baseline up to 36 months

  2. Progression free survival (PFS)

    Estimate progression free survival (PFS) for valemetostat when administered with atezolizumab and bevacizumab in advanced HCC.

    Measured: Baseline until the date of objective disease progression or death.

  3. Overall survival (OS)

    Estimate overall survival (OS) for valemetostat when administered with atezolizumab and bevacizumab in advanced HCC.

    Measured: Baseline up to 48 months

  4. Duration of response (DoR)

    Estimate duration of response (DoR) for valemetostat when administered with atezolizumab and bevacizumab in advanced HCC.

    Measured: Baseline up to 48 months

  5. Disease Control Rate (DCR)

    Estimate the disease control rate (DCR) for valemetostat when administered with atezolizumab and bevacizumab in advanced HCC.

    Measured: Baseline up to 48 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Mar 2024
  2. Study start29 Jul 2025
  3. Primary completion30 Jan 2028 (estimated)
  4. Study completion28 Aug 2028 (estimated)

Resources

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
45 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06294548
Sponsor's protocol ID
IRB-300012272 (UAB 23152)
Other IDs
Daiichi Sankyo Pharma Dev
Status last verified
Aug 2026
First submitted
28 Feb 2024
Last updated
1 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Valemetostat, Atezolizumab and Bevacizumab in people with Hepatocellular Carcinoma, run by University of Alabama at Birmingham at 1 site in United States.

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 37 inclusion and 54 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: looking for participants now, as of the sponsor's last update on 1 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Margaret Thomas, MPH (205-895-1802, margaretannthomas@uabmc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase 1b (time frame: Baseline up to 36 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06294548.

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 1 Sep 2026.

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