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

NCT06294548 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: IRB-300012272 (UAB 23152)
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (2)

• Phase 1b

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

  Baseline up to 36 months

• 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).

  Baseline up to 36 months

Secondary Outcomes (5)

• Safety and pharmacokinetics (PK)

  Baseline up to 36 months

• Progression free survival (PFS)

  Baseline until the date of objective disease progression or death.

• Overall survival (OS)

  Baseline up to 48 months

• Duration of response (DoR)

  Baseline up to 48 months

• Disease Control Rate (DCR)

  Baseline up to 48 months

Study Arms (2)

Phase 1b: Valemetostat + Atezolizumab 1200 mg + Bevacizumab 15 mg/kg

EXPERIMENTAL

In 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.

Drug: Valemetostat; Drug: Atezolizumab; Drug: Bevacizumab

Phase II: Valemetostat + Atezolizumab 1200 mg + Bevacizumab 15 mg/kg

EXPERIMENTAL

During 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.

Drug: Valemetostat; Drug: Atezolizumab; Drug: Bevacizumab

Interventions

Valemetostat DRUG

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

Also known as: Valemetostat tosylate, Valemetostat (DS-3201)

Phase 1b: Valemetostat + Atezolizumab 1200 mg + Bevacizumab 15 mg/kg; Phase II: Valemetostat + Atezolizumab 1200 mg + Bevacizumab 15 mg/kg

Atezolizumab DRUG

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.

Phase 1b: Valemetostat + Atezolizumab 1200 mg + Bevacizumab 15 mg/kg; Phase II: Valemetostat + Atezolizumab 1200 mg + Bevacizumab 15 mg/kg

Bevacizumab DRUG

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.

Phase 1b: Valemetostat + Atezolizumab 1200 mg + Bevacizumab 15 mg/kg; Phase II: Valemetostat + Atezolizumab 1200 mg + Bevacizumab 15 mg/kg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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.

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

Sponsors & Collaborators

• University of Alabama at Birmingham: lead

Study Sites (1)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

atezolizumab; Bevacizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Mehmet Akce, MD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Margaret Thomas, MPH

CONTACT

205-895-1802; margaretannthomas@uabmc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: February 28, 2024
• First Posted: March 5, 2024
• Study Start: July 29, 2025
• Primary Completion (Estimated): January 30, 2028
• Study Completion (Estimated): August 28, 2028
• Last Updated: August 11, 2025

Record last verified: 2025-08

Locations

US (1)