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

Recruiting now · Phase 1/Phase 2

Conditions studied: Hepatocellular Carcinoma

In brief

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.

Key facts

Study ID

NCT06294548

Run by

University of Alabama at Birmingham

People needed

45

Starts

2025-07-29

Expected to finish

2028-08-28

Last updated by the study team

2025-08-11

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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.
• 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.

You may not qualify if…

• 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.
• 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

Where it is running

• University of Alabama at Birmingham — Birmingham, Alabama, United States (enrolling)

Full record on ClinicalTrials.gov

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