Unresectable Hepatocellular CarcinomaPhase 1/2NCT07835737
Safety and Efficacy of Folic Acid Combined With Atezolizumab and Bevacizumab as First-Line Therapy for Unresectable Hepatocellular Carcinoma
A Phase 1/2 study testing Folic Acid and Atezolizumab & Bevacizumab in people with Unresectable Hepatocellular Carcinoma, run by West China Hospital.
Trial summary
This study is evaluating the safety and potential effectiveness of adding folic acid to atezolizumab plus bevacizumab as first-line treatment for adults with unresectable hepatocellular carcinoma (HCC). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Unresectable Hepatocellular Carcinoma
- What is being tested?
- Folic Acid and Atezolizumab & Bevacizumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 78 participants
- Where
- No sites listed yet
- Study dates
- 1 Oct 2026to 1 Oct 2029
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 to 75 years, male or female, and willing to provide written informed consent.
- Hepatocellular carcinoma (HCC) confirmed by histologic/cytologic examination or diagnosed according to accepted guideline-based clinical criteria.
- Unresectable HCC as determined by multidisciplinary evaluation; BCLC stage B disease that is unsuitable for, declined, or has progressed after locoregional treatment, or BCLC stage C disease; candidate for first-line systemic therapy.
- No prior systemic anticancer therapy for unresectable HCC. Prior locoregional treatment must have been completed at least 4 weeks before the first study treatment, with treatment-related toxicities recovered to Grade ≤1 or baseline.
- At least one measurable lesion according to RECIST version 1.1. The measurable lesion must not have received prior locoregional treatment unless unequivocal radiologic progression has subsequently occurred.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and life expectancy of at least 12 weeks.
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- Child-Pugh class A (score 5-6), without clinically decompensated ascites or hepatic encephalopathy.
- Adequate bone marrow function: absolute neutrophil count ≥1.5 × 10^9/L, platelet count ≥75 × 10^9/L, and hemoglobin ≥90 g/L.
- Adequate hepatic and renal function: total bilirubin ≤3 × upper limit of normal (ULN); AST and ALT ≤5 × ULN; albumin ≥28 g/L; INR ≤1.5; serum creatinine ≤1.5 × ULN or creatinine clearance ≥50 mL/min.
- Urine protein dipstick ≤1+. If urine protein is ≥2+, 24-hour urinary protein must be <1 g. Blood pressure must be adequately controlled at ≤150/90 mmHg.
- Upper gastrointestinal endoscopic evaluation within 6 months before the first study treatment. Intermediate- or high-risk gastroesophageal varices must have been appropriately managed and considered to have an acceptable bleeding risk by the investigator.
- Participants with positive HBsAg or detectable HBV DNA must receive appropriate antiviral therapy and have HBV DNA <500 IU/mL before the first study treatment. HCV infection must be clinically stable.
- Serum vitamin B12 at or above the institutional lower limit of normal, with no uncorrected megaloblastic anemia or progressive unexplained neurologic symptoms.
- Participants of reproductive potential must agree to use highly effective contraception according to protocol requirements.
Who cannot join
- Prior treatment with PD-1, PD-L1, CTLA-4, or other immune checkpoint inhibitors, or prior bevacizumab treatment for HCC.
- Eligible for curative resection, ablation, or liver transplantation and willing to undergo such treatment.
- Active or recent clinically significant bleeding, including gastrointestinal bleeding, hemoptysis, or other Grade ≥2 bleeding within 6 months before the first study treatment, or untreated high-risk varices.
- Arterial thromboembolism, myocardial infarction, unstable angina, stroke/transient ischemic attack, severe arrhythmia, or NYHA class >II heart failure within 6 months before the first study treatment.
- Tumor invasion of major blood vessels considered by the investigator to confer a significant near-term risk of fatal bleeding, or clinically significant risk of tumor rupture.
- Uncontrolled hypertension, clinically significant proteinuria, active peptic ulcer disease, high risk of gastrointestinal perforation or fistula, unhealed wound, or major surgery within 28 days before the first study treatment.
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- Active autoimmune disease requiring systemic treatment, or systemic corticosteroid therapy equivalent to prednisone >10 mg/day or other immunosuppressive therapy within 14 days before the first study treatment, except physiologic replacement therapy.
- Prior solid-organ transplantation or allogeneic hematopoietic stem-cell transplantation.
- Active severe infection, including uncontrolled HBV or HCV infection, active tuberculosis, or HIV infection associated with clinically significant immunodeficiency.
- Symptomatic, untreated, or unstable central nervous system metastases.
- Vitamin B12 deficiency, pernicious anemia, folic acid hypersensitivity, or continuous use of folic acid >0.4 mg/day within 14 days before screening that cannot be discontinued.
- Current use of methotrexate or other antifolate drugs, or use of phenytoin, phenobarbital, or primidone that cannot be replaced or appropriately monitored.
- Pregnancy or breastfeeding; serious concurrent disease, psychiatric or cognitive disorder, or compliance issue that could interfere with study participation.
- Participation in another interventional clinical study within 4 weeks before the first study treatment, or any other condition considered by the investigator to make the participant unsuitable for enrollment.
About this study
Official title: Safety and Efficacy of Folic Acid Combined With Atezolizumab and Bevacizumab as First-Line Therapy for Unresectable Hepatocellular Carcinoma: A Prospective, Open-Label, Single-Arm, Phase Ib/II Clinical Trial
This study is evaluating the safety and potential effectiveness of adding folic acid to atezolizumab plus bevacizumab as first-line treatment for adults with unresectable hepatocellular carcinoma (HCC).
The main questions this study aims to answer are:
Read more
Is daily folic acid safe and well tolerated when given together with atezolizumab and bevacizumab? What dose of folic acid should be recommended for further study? Does the combination show sufficient antitumor activity to support further clinical testing?
This is an open-label, single-arm phase Ib/II study. All participants will receive folic acid together with atezolizumab and bevacizumab. There is no placebo or separate control group.
Participants will:
Take folic acid by mouth once daily, starting 7 days before the first dose of atezolizumab and bevacizumab.
Receive atezolizumab and bevacizumab by intravenous infusion every 3 weeks. Attend regular clinic visits for physical examinations, blood tests, safety assessments, and tumor imaging.
Have tumor imaging every 6 weeks during the first 24 weeks and every 9 weeks thereafter.
Provide blood samples for exploratory biomarker studies. An additional tumor biopsy during treatment may be offered but is optional.
Treatment will continue until disease progression, unacceptable side effects, withdrawal of consent, or another protocol-defined reason for stopping treatment. Immunotherapy may be continued for up to 24 months.
- Conditions
- Unresectable Hepatocellular Carcinoma
- Being tested
- Folic Acid, Atezolizumab & Bevacizumab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Folic AcidDrug
Folic acid will be administered orally once daily, beginning 7 days before the first administration of atezolizumab and bevacizumab. During phase Ib, sequential dose levels of 1 mg once daily and 5 mg once daily will be evaluated to determine the recommended phase II dose (RP2D). In the phase II expansion, participants will receive folic acid at the selected RP2D.
Atezolizumab & BevacizumabDrug
Atezolizumab 1200 mg and bevacizumab 15 mg/kg will be administered by intravenous infusion on Day 1 of each 3-week treatment cycle.
| Study group | Role | What they receive |
|---|---|---|
| Folic Acid Plus Atezolizumab and Bevacizumab | Experimental | All participants will receive folic acid in combination with atezolizumab and bevacizumab. During the phase Ib dose-finding portion, sequential cohorts will receive folic acid 1 mg once daily or 5 mg once daily, starting 7 days before the first administration of atezolizumab and bevacizumab, to determine the recommended phase II dose (RP2D). In the phase II expansion, participants will receive folic acid at the selected RP2D. Atezolizumab 1200 mg and bevacizumab 15 mg/kg will be administered intravenously on Day 1 of each 3-week cycle. Receives: Drug: Folic Acid; Drug: Atezolizumab & Bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Dose-Limiting Toxicities (DLTs) During Phase Ib
The number and proportion of participants experiencing a protocol-defined dose-limiting toxicity (DLT). DLTs will be graded according to NCI CTCAE version 6.0 and adjudicated according to protocol-defined attribution criteria.
Measured: From the first folic acid dose on Day -7 through Cycle 1 Day 21 (28 days)
Recommended Phase II Dose (RP2D) of Folic Acid
The recommended phase II dose of folic acid will be selected based on the integrated assessment of dose-limiting toxicities, overall safety and tolerability, treatment adherence, serum folate exposure, and pharmacodynamic findings during the phase Ib dose-finding portion.
Measured: At completion of the Phase Ib dose-finding portion, approximately up to 10 months after study initiation
Objective Response Rate (ORR) by Blinded Independent Central Review per RECIST Version 1.1
The proportion of participants treated at the recommended phase II dose whose best overall response is a confirmed complete response (CR) or partial response (PR), as assessed by blinded independent central review (BICR) according to RECIST version 1.1. A response must be confirmed by a subsequent assessment at least 4 weeks later.
Measured: From the first study treatment until documented disease progression or initiation of new anticancer therapy, up to 24 months
Secondary outcomes (12)
Objective Response Rate per mRECIST
Proportion of participants with a confirmed complete response (CR) or partial response (PR) according to modified RECIST criteria for hepatocellular carcinoma.
Measured: Up to 24 months
Investigator-Assessed Objective Response Rate per RECIST 1.1
Proportion of participants with a confirmed CR or PR according to investigator assessment using RECIST version 1.1.
Measured: Up to 24 months
Disease Control Rate (DCR)
Proportion of participants achieving CR, PR, or stable disease according to RECIST version 1.1.
Measured: Up to 24 months
Duration of Response (DOR)
Time from the first documented CR or PR to disease progression or death from any cause.
Measured: Up to approximately 36 months
Time to Response (TTR)
Time from the first study treatment to the first documented CR or PR.
Measured: Up to 24 months
Progression-Free Survival (PFS)
Time from the first study treatment to disease progression according to RECIST version 1.1 or death from any cause, whichever occurs first.
Measured: Up to approximately 36 months
Progression-Free Survival Rates at 6 and 12 Months
Proportion of participants alive without disease progression at 6 months and 12 months after initiation of study treatment.
Measured: 6 months and 12 months
Overall Survival (OS)
Time from the first study treatment to death from any cause.
Measured: Up to approximately 36 months
Overall Survival Rates at 12 and 24 Months
Proportion of participants alive at 12 months and 24 months after initiation of study treatment.
Measured: 12 months and 24 months
AFP Response Rate
Proportion of evaluable participants with a decrease in serum alpha-fetoprotein (AFP) of at least 20% from baseline.
Measured: Up to 24 months
Conversion to Curative Surgical Resection
Proportion of participants who become eligible for and undergo protocol-defined R0 surgical resection after multidisciplinary evaluation.
Measured: Up to 24 months
Incidence of Adverse Events
Incidence and severity of adverse events, serious adverse events, treatment-related adverse events, immune-related adverse events, and adverse events leading to treatment interruption or discontinuation, graded according to NCI CTCAE version 6.0.
Measured: From informed consent through protocol-defined safety follow-up; immune-related adverse events monitored for at least 90 days after the last dose of atezolizumab
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Sep 2026
- Study start1 Oct 2026 (estimated)
- Primary completion1 Oct 2029 (estimated)
- Study completion1 Oct 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Unresectable Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by West China HospitalThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 78 participants (estimated)
Sponsor and investigators
- Lead sponsor
- West China Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Hong Wu, West China Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07835737
- Sponsor's protocol ID
- 2026(1164)
- Status last verified
- Sep 2026
- First submitted
- 10 Sep 2026
- Last updated
- 23 Sep 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficacy of Folic Acid Combined With Atezolizumab and Bevacizumab as First-Line Therapy for Unresectable Hepatocellular Carcinoma: A Prospective, Open-Label, Single-Arm, Phase Ib/II Clinical Trial
- ClinicalTrials.gov ID
- NCT07835737
- Acronym / sponsor ID
- 2026(1164)
- Conditions
- Unresectable Hepatocellular Carcinoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 78 participants (estimated)
- Lead sponsor
- West China HospitalUniversity, hospital or other
- Study start
- 1 Oct 2026 (estimated)
- Primary completion
- 1 Oct 2029 (estimated)
- Study completion
- 1 Oct 2029 (estimated)
- First posted
- 23 Sep 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.
This study is evaluating the safety and potential effectiveness of adding folic acid to atezolizumab plus bevacizumab as first-line treatment for adults with unresectable hepatocellular carcinoma (HCC).
The main questions this study aims to answer are:
Is daily folic acid safe and well tolerated when given together with atezolizumab and bevacizumab? What dose of folic acid should be recommended for further study? Does the combination show sufficient antitumor activity to support further clinical testing?
This is an open-label, single-arm phase Ib/II study. All participants will receive folic acid together with atezolizumab and bevacizumab. There is no placebo or separate control group.
Participants will:
Take folic acid by mouth once daily, starting 7 days before the first dose of atezolizumab and bevacizumab.
Receive atezolizumab and bevacizumab by intravenous infusion every 3 weeks. Attend regular clinic visits for physical examinations, blood tests, safety assessments, and tumor imaging.
Have tumor imaging every 6 weeks during the first 24 weeks and every 9 weeks thereafter.
Provide blood samples for exploratory biomarker studies. An additional tumor biopsy during treatment may be offered but is optional.
Treatment will continue until disease progression, unacceptable side effects, withdrawal of consent, or another protocol-defined reason for stopping treatment. Immunotherapy may be continued for up to 24 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Folic Acid Plus Atezolizumab and Bevacizumab | Experimental | Drug: Folic Acid, Drug: Atezolizumab & BevacizumabAll participants will receive folic acid in combination with atezolizumab and bevacizumab. During the phase Ib dose-finding portion, sequential cohorts will receive folic acid 1 mg once daily or 5 mg once daily, starting 7 days before the first administration of atezolizumab and bevacizumab, to determine the recommended phase II dose (RP2D). In the phase II expansion, participants will receive folic acid at the selected RP2D. Atezolizumab 1200 mg and bevacizumab 15 mg/kg will be administered intravenously on Day 1 of each 3-week cycle. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Age 18 to 75 years, male or female, and willing to provide written informed consent.
- Hepatocellular carcinoma (HCC) confirmed by histologic/cytologic examination or diagnosed according to accepted guideline-based clinical criteria.
- Unresectable HCC as determined by multidisciplinary evaluation; BCLC stage B disease that is unsuitable for, declined, or has progressed after locoregional treatment, or BCLC stage C disease; candidate for first-line systemic therapy.
- No prior systemic anticancer therapy for unresectable HCC. Prior locoregional treatment must have been completed at least 4 weeks before the first study treatment, with treatment-related toxicities recovered to Grade ≤1 or baseline.
- At least one measurable lesion according to RECIST version 1.1. The measurable lesion must not have received prior locoregional treatment unless unequivocal radiologic progression has subsequently occurred.
Key exclusion criteria (14 listed)
- Prior treatment with PD-1, PD-L1, CTLA-4, or other immune checkpoint inhibitors, or prior bevacizumab treatment for HCC.
- Eligible for curative resection, ablation, or liver transplantation and willing to undergo such treatment.
- Active or recent clinically significant bleeding, including gastrointestinal bleeding, hemoptysis, or other Grade ≥2 bleeding within 6 months before the first study treatment, or untreated high-risk varices.
- Arterial thromboembolism, myocardial infarction, unstable angina, stroke/transient ischemic attack, severe arrhythmia, or NYHA class >II heart failure within 6 months before the first study treatment.
- Tumor invasion of major blood vessels considered by the investigator to confer a significant near-term risk of fatal bleeding, or clinically significant risk of tumor rupture.
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 |
|---|---|---|
| Folic AcidFolic acid will be administered orally once daily, beginning 7 days before the first administration of atezolizumab and bevacizumab. During phase Ib, sequential dose levels of 1 mg once daily and 5 mg once daily will be evaluated to determine the recommended phase II dose (RP2D). In the phase II expansion, participants will receive folic acid at the selected RP2D. | Drug | Folic Acid Plus Atezolizumab and Bevacizumab |
| Atezolizumab & BevacizumabAtezolizumab 1200 mg and bevacizumab 15 mg/kg will be administered by intravenous infusion on Day 1 of each 3-week treatment cycle. | Drug | Folic Acid Plus Atezolizumab and Bevacizumab |
Primary outcome
Incidence of Dose-Limiting Toxicities (DLTs) During Phase Ib
Time frame: From the first folic acid dose on Day -7 through Cycle 1 Day 21 (28 days)
The number and proportion of participants experiencing a protocol-defined dose-limiting toxicity (DLT). DLTs will be graded according to NCI CTCAE version 6.0 and adjudicated according to protocol-defined attribution criteria.
Recommended Phase II Dose (RP2D) of Folic Acid
Time frame: At completion of the Phase Ib dose-finding portion, approximately up to 10 months after study initiation
The recommended phase II dose of folic acid will be selected based on the integrated assessment of dose-limiting toxicities, overall safety and tolerability, treatment adherence, serum folate exposure, and pharmacodynamic findings during the phase Ib dose-finding portion.
Objective Response Rate (ORR) by Blinded Independent Central Review per RECIST Version 1.1
Time frame: From the first study treatment until documented disease progression or initiation of new anticancer therapy, up to 24 months
The proportion of participants treated at the recommended phase II dose whose best overall response is a confirmed complete response (CR) or partial response (PR), as assessed by blinded independent central review (BICR) according to RECIST version 1.1. A response must be confirmed by a subsequent assessment at least 4 weeks later.
12 secondary outcomes
Objective Response Rate per mRECIST
Time frame: Up to 24 months
Investigator-Assessed Objective Response Rate per RECIST 1.1
Time frame: Up to 24 months
Disease Control Rate (DCR)
Time frame: Up to 24 months
Duration of Response (DOR)
Time frame: Up to approximately 36 months
Time to Response (TTR)
Time frame: Up to 24 months
Progression-Free Survival (PFS)
Time frame: Up to approximately 36 months
Progression-Free Survival Rates at 6 and 12 Months
Time frame: 6 months and 12 months
Overall Survival (OS)
Time frame: Up to approximately 36 months
Overall Survival Rates at 12 and 24 Months
Time frame: 12 months and 24 months
AFP Response Rate
Time frame: Up to 24 months
Conversion to Curative Surgical Resection
Time frame: Up to 24 months
Incidence of Adverse Events
Time frame: From informed consent through protocol-defined safety follow-up; immune-related adverse events monitored for at least 90 days after the last dose of atezolizumab
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Sep 2026.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Folic Acid and Atezolizumab & Bevacizumab in people with Unresectable Hepatocellular Carcinoma, run by West China Hospital.
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 14 inclusion and 14 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: opening soon, as of the sponsor's last update on 23 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 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?
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?
Incidence of Dose-Limiting Toxicities (DLTs) During Phase Ib (time frame: From the first folic acid dose on Day -7 through Cycle 1 Day 21 (28 days)). The study lists 3 primary outcomes in all. 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 23 Sep 2026; AzTrials last refreshed its copy on 8 Nov 2026.