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Carcinoma, HepatocellularPhase 1/2NCT05908786

A Study Evaluating The Efficacy and Safety of Neoadjuvant Immunotherapy Combinations in Patients With Surgically Resectable Hepatocellular Carcinoma

A Phase 1/2 study testing Atezolizumab, Bevacizumab and Tiragolumab in people with Carcinoma, Hepatocellular, run by Hoffmann-La Roche at 14 sites in 6 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

This is a Phase Ib/II, open-label, multicenter, randomized platform study to evaluate neoadjuvant immunotherapy combinations in participants with resectable HCC. The study is designed with the flexibility to open new treatment arms as new agents become available, close existing treatment arms that demonstrate minimal… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Carcinoma, Hepatocellular
What is being tested?
Atezolizumab, Bevacizumab and Tiragolumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
62 participants
Where
14 sitesin 6 countries
Study dates
5 Dec 2023to 13 Nov 2025
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 HCC confirmed either histologically or clinically according to AASLD criteria for patients with cirrhosis. For participants without cirrhosis, histological confirmation is mandatory.
  • HCC that is amenable to R0 surgical resection with curative intent in the opinion of the surgeons and oncologists or hepatologists involved in the care of the participant. Patients presenting with resectable HCC within or beyond Milan criteria (without extrahepatic spread or macrovascular invasion) are eligible.
  • Measurable disease (at least one target lesion) according to RECIST v1.1 as determined by the investigator
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 within 7 days prior to randomization
  • Child-Pugh Class A within 7 days prior to randomization
  • Negative HIV test at screening
Show all 36Show fewer
  • No prior locoregional or systemic treatment for HCC
  • Adequate hematologic and end-organ function
  • Documented virology status of hepatitis
  • For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception
  • For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agreement to refrain from donating sperm
  • General Exclusion Criteria:
  • Presence of extrahepatic disease or macrovascular invasion
  • Known fibrolamellar HCC, sarcomatoid HCC, mixed cholangiocarcinoma and HCC, or other rare variants of HCC
  • History of hepatic encephalopathy if clinically significant within one year prior to initiation of study treatment
  • Moderate or severe ascites
  • Active co-infection with HBV and HCV
  • Known active co-infection with HBV and hepatitis D viral infection
  • Prior treatment with CD137 agonists or immune checkpoint inhibitors, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
  • Treatment with investigational therapy within 28 days prior to initiation of study treatment
  • Untreated or incompletely treated esophageal and/or gastric varices with bleeding or that are at high risk for bleeding
  • A prior bleeding event due to esophageal and/or gastric varices within 6 months prior to initiation of study treatment
  • Inadequately controlled hypertension
  • History of hypertensive crisis or hypertensive encephalopathy
  • Significant vascular disease within 6 months prior to initiation of study treatment
  • History of hemoptysis within 1 month prior to initiation of study treatment
  • Evidence of bleeding diathesis or significant coagulopathy
  • Current or recent (<= 10 days prior to initiation of study treatment) use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic purposes
  • History of abdominal or tracheoesophageal fistula, GI perforation or intra-abdominal abscesses within 6 months prior to initiation of study treatment
  • History of intestinal obstruction and/or clinical sign or symptoms of GI obstruction
  • Serious, non-healing or dehiscing wound, active ulcer, or untreated bone fracture
  • Grade >= proteinuria
  • Major surgical procedure, open biopsy, or significant traumatic injury, or abdominal surgery, interventions or traumatic injuries, or anticipation of need of major surgical procedure other than potentially curative liver resection
  • Chronic daily treatment with a non-steroidal anti-inflammatory drug (NSAID)
  • Serious infection requiring oral or IV antibiotics and/or hospitalization
  • Active tuberculosis

Who cannot join

None listed.

Trial locations and contacts

14 sites in 6 countries.

14 sites in 6 countries

United States5 sites

  • UT Southwestern Medical Center

    Dallas, Texas, 75390-8813

  • University of Southern California (USC)

    Los Angeles, California, 90033

  • Columbia University Medical Center

    New York, New York, 10032

  • University of California Los Angeles (UCLA) - Cancer Care - Santa Monica

    Santa Monica, California, 90404-2023

  • Georgetown University Medical Center

    Washington D.C., District of Columbia, 20007

Other trials in United States

Austria2 sites

  • Klinikum Klagenfurt am Wörthersee

    Klagenfurt, 9020

  • Department of Internal Medicine III AKH and Medical University of Vienna

    Vienna, 1090

Other trials in Austria

France2 sites

  • Centre Georges Francois Leclerc (CGFL)

    Dijon, 21079

  • Gustave Roussy

    Villejuif, 94800

Other trials in France

Germany2 sites

  • University Essen

    Essen, 45147

  • Universitaets Klinikum Frankfurt - Zentrum der Inneren Medizin

    Frankfurt, 60596

Other trials in Germany

Spain2 sites

  • Hospital Universitario Fundacion Jimenez Diaz.

    Madrid, 28040

  • Hospital Universitario Marques de Valdecilla

    Santander, Cantabria, 39008

Other trials in Spain

United Kingdom1 site

  • Imperial College London - Imperial Centre for Translational and Experimental Medicine (ICTEM)

    London

Other trials in United Kingdom

About this study

Official title: A Phase Ib/II, Open-Label, Multicenter, Randomized Platform Study Evaluating The Efficacy and Safety of Neoadjuvant Immunotherapy Combinations in Patients With Surgically Resectable Hepatocellular Carcinoma (MORPHEUS-NEO HCC)

This is a Phase Ib/II, open-label, multicenter, randomized platform study to evaluate neoadjuvant immunotherapy combinations in participants with resectable HCC. The study is designed with the flexibility to open new treatment arms as new agents become available, close existing treatment arms that demonstrate minimal clinical activity or unacceptable toxicity, or modify the participant population.

Being tested
Atezolizumab, Bevacizumab, Tiragolumab, Tobemstomig
Medical subject headings
Carcinoma, Hepatocellular

What participants receive

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

  • AtezolizumabDrug

    Also called Tecentriq

    Atezolizumab will be administered at a dose of 1200 mg by IV infusion on Day 1.

  • BevacizumabDrug

    Also called Avastin

    Bevacizumab will be administered at a dose of 15 mg/kg by IV infusion on Day 1.

  • TiragolumabDrug

    Tiragolumab will be administered at a dose of 600 mg by IV infusion on Day 1.

  • TobemstomigDrug

    Also called RO7247669

    Tobemstomig will be administered at a dose of 600 mg by IV infusion on Day 1

Study groups in NCT05908786
Study groupRoleWhat they receive
Atezo + BevExperimentalParticipants in the atezolizumab plus bevacizumab (Atezo + Bev) arm will receive up to three cycles of treatment until surgery or unacceptable toxicity, whichever occurs first.
Receives: Drug: Atezolizumab; Drug: Bevacizumab
Atezo + Bev +TiraExperimentalParticipants in the atezolizumab plus bevacizumab plus tiragolumab (Atezo + Bev +Tira) arm will receive up to three cycles of treatment until surgery or unacceptable toxicity, whichever occurs first.
Receives: Drug: Atezolizumab; Drug: Bevacizumab; Drug: Tiragolumab
Tobe + BevExperimentalParticipants in the Tobemstomig + Bev arm will receive up to three cycles of treatment until surgery or unacceptable toxicity, whichever occurs first. Enrollment is closed.
Receives: Drug: Bevacizumab; Drug: Tobemstomig

What is being measured

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

  1. Major Pathologic Response (MPR) Rate

    MPR rate was defined as the percentage of participants who had achieved MPR and was estimated for each treatment cohort in the efficacy-evaluable population. MPR was defined as ≤ 10% residual viable tumor in the tumor bed at the time of surgical resection in the primary tumor, as assessed by the central pathology laboratory. Participants who did not proceed to surgery were considered as non-responders for MPR. Percentages have been rounded off.

    Measured: At the time of surgery (up to 15 weeks)

Secondary outcomes (19)

  1. Pathologic Complete Response (pCR) Rate

    pCR rate was defined as the percentage of participants who had achieved pCR. pCR was defined as the absence of any viable tumor cells in both the primary tumor and all sampled lymph nodes at the time of surgical resection, as assessed by central pathological review. Percentages have been rounded off.

    Measured: At the time of surgery (up to 15 weeks)

  2. Relapse-free Survival (RFS), as Assessed by the Investigator According to European Association for the Study of the Liver (EASL) and/or Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)

    RFS was defined as the time from surgery to the first documented recurrence of disease (intrahepatic or extrahepatic), as assessed by the investigator according to EASL and/or RECIST v1.1, or death from any cause. Intrahepatic recurrence was defined by the appearance of one or more intrahepatic lesions with a longest diameter of > 1 cm and a typical vascular pattern of HCC on dynamic imaging (i.e., hypervascularization in the arterial phase with washout in the portal venous or late venous phase). Extrahepatic recurrence was assessed by RECIST v1.1 as the appearance of new, measurable malignant lesions outside the liver. Data for participants who did not have documented recurrence of disease or death were censored at the day of the last tumor assessment for participants. Kaplan-Meier (K-M) method was used to estimate median RFS.

    Measured: From surgery to the first documented recurrence of disease (up to 20.5 months)

  3. Event-free Survival (EFS), as Assessed by the Investigator According to EASL and RECIST v1.1

    EFS was defined as the time from randomization to any of the following events, whichever occurred first: PD that precluded surgery, as assessed by the investigator according to RECIST v1.1. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters at prior timepoints (including baseline); local, regional, or distant disease recurrence as measured by EASL and/or RECIST v1.1; or death from any cause. Data for participants who had not experienced EFS events were censored at the time of their last post-surgical tumor assessment. K-M method was used to estimate median RFS.

    Measured: From randomization to PD that precluded surgery or disease recurrence or death from any cause, whichever occurred first (up to 20.5 months)

  4. Overall Survival (OS)

    OS was defined as the time from randomization to death from any cause. Data for participants who had not died were censored at the last date they were known to be alive. K-M method was used to estimate median OS.

    Measured: From randomization to death from any cause (up to 20.5 months)

  5. OS Rate at 6 Months, 12 Months, and 18 Months

    OS rate at 6, 12, and 18 months was defined as the percentage of participants who had not experienced death from any cause at 6 months, 12 months, and 18 months after randomization, respectively. OS was defined as the time from randomization to death from any cause. K-M method was used to estimate OS rate. Percentages have been rounded off. Due to the low number of events the results need to be interpreted with caution.

    Measured: At Months 6, 12, and 18

  6. Objective Response Rate (ORR), as Assessed by the Investigator According to RECIST v1.1

    ORR was defined as the percentage of participants with a radiographic objective response (OR), characterized by a complete response (CR) or a partial response (PR) prior to surgery, as determined by the investigator according to RECIST v1.1. CR was defined as the disappearance of all target and non-target lesions. Additionally, any pathological lymph nodes (whether target or non-target) must have a reduction in short axis to <10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters (SOD) of all target lesions, taking as reference the baseline SOD, in the absence of CR. Percentages have been rounded off.

    Measured: Prior to surgery (at approximately Week 11)

  7. ORR, as Assessed by the Investigator According to Hepatocellular Carcinoma-Specific Modified Response Evaluation Criteria in Solid Tumors (HCC mRECIST)

    ORR was defined as the percentage of participants with a radiographic OR, characterized by a CR or a PR prior to surgery, as determined by the investigator according to HCC mRECIST. CR was defined as the disappearance of any intratumoral arterial enhancement in all target and non-target lesions. PR was defined as an increase of at least 30% in the sum of the longest diameters of viable (contrast enhancement in the arterial phase) target lesions, taking as reference the baseline SOD of target lesions. Percentages have been rounded off.

    Measured: Prior to surgery (at approximately Week 11)

  8. Percentage of Participants Downstaged to Within Milan Criteria (for Participants Beyond Criteria at Randomization)

    Percentage of participants downstaged to within Milan Criteria was defined as the number of participants who were beyond Milan criteria at enrollment and staged as within Milan criteria (single tumor ≤ 5 or 2 to 3 nodules all ≤ 3 centimeters [cm]) during the study. Milan criteria=single tumor > 5 cm or 2 to 3 nodules > 3 cm, or ≥ 4 nodules. Percentages have been rounded off.

    Measured: At the time of surgery (up to 15 weeks)

  9. Negative Surgical Margins (R0) Resection Rate

    R0 resection rate was defined as the percentage of resected participants who achieved complete resection (R0 resection), confirmed by pathology. R0 resection was defined as a microscopically margin-negative resection, in which no tumor (gross or microscopic) remains in the primary tumor bed. Percentages have been rounded off.

    Measured: At the time of surgery (up to 15 weeks)

  10. Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Immune-related AEs

    An AE was defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any AE that meets any of the following criteria: Is fatal; Is life threatening; Requires or prolongs inpatient hospitalization; Results in persistent or significant disability/incapacity; Is a congenital anomaly/birth defect in a neonate/infant born to a mother exposed to study treatment; Is a significant medical event in the investigator's judgment. Participants with immune-mediated Hepatitis (Diagnosis and Lab Abnormalities) have been reported as immune-related AEs.

    Measured: From initiation of study treatment up to 135 days (Serious AEs and AESI) or 30 days (all other AEs) after the final dose of study treatment or until initiation of new systemic anti-cancer therapy (up to 7.7 moths)

  11. Percentage of Participants With Delayed or Cancelled Surgery Due to Treatment-related Adverse Events (TRAEs)

    Delayed Surgery was defined as delay in surgery by > 28 days from the surgical restaging or pre-surgery visit. Percentages have been rounded off.

    Measured: Assessed at pre-surgery (scheduled at Week 11)

  12. Length of Surgical Delays

    Delayed Surgery was defined as a delay in surgery by > 28 days from the surgical restaging or pre-surgery visit.

    Measured: Assessed at pre-surgery (scheduled at Week 11) up to 20 weeks

  13. Duration of Surgery

    Measured: At the time of surgery (up to 15 weeks)

  14. Duration of Hospital Stay Post-surgery

    Measured: From time of surgery (15 weeks) up to 6 weeks (± 2 weeks) post-surgery (up to 23 weeks)

  15. Number of Participants With Specific Surgical Approach

    The surgical approach was categorized as: Hemihepatectomy; Sectionectomy; Segmentectomy; Other.

    Measured: At the time of surgery (up to 15 weeks)

  16. Intraoperative Blood Loss

    Measured: At the time of surgery (up to 15 weeks)

  17. Number of Participants Needing Intraoperative Blood Transfusion

    Measured: At the time of surgery (up to 15 weeks)

  18. Post-operative Surgical Complication Rates Assessed According to the Clavien-dindo Surgical Classification

    Clavien-dindo Surgical Classification graded surgical complications as: Grade I- Any complication that does not need pharmacological treatment or surgical, endoscopic, \& radiological interventions; Grade II- Complications requiring pharmacological treatment with drugs other than such allowed for Grade I complications or complications requiring blood transfusions \& total parenteral nutrition; Grade III- Complications requiring surgical, endoscopic, or radiological intervention with (Grade IIIb) or without (Grade IIIa) general anesthesia; Grade IV- Life-threatening complications requiring intensive care unit (ICU) management, which may be single organ (Grade IVa) or multiorgan (Grade IVb) dysfunction; Grade V- Complications causing death. The percentage of participants with any post-surgical complications specifically related to the HCC resection was reported. Percentages have been rounded off.

    Measured: From time of surgery (15 weeks) up to neo-adjuvant treatment completion/discontinuation (6 weeks [± 2 weeks]) (up to 23 weeks)

  19. Number of Participants With Post-operative Mortality

    Measured: From surgery (15 weeks) up to 90 days post-surgery (up to 27.8 weeks)

Timeline

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

  1. First posted18 Jun 2023
  2. Study start5 Dec 2023
  3. Primary completion27 Aug 2025
  4. Study completion13 Nov 2025

Why it stopped: Study was closed early as the sponsor decided not to continue development of certain treatment combinations.

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
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
62 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05908786
Sponsor's protocol ID
GO44457
Status last verified
Aug 2026
First submitted
7 Jun 2023
Last updated
15 Sep 2026
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data\_sharing

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Atezolizumab, Bevacizumab and Tiragolumab in people with Carcinoma, Hepatocellular, run by Hoffmann-La Roche at 14 sites in 6 countries.

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 36 inclusion and 0 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: stopped early, as of the sponsor's last update on 15 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 14 sites in United States, Austria, France, Germany, Spain and 1 more country. 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?

Yes. Results are posted in the registry (first posted 15 Sep 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Major Pathologic Response (MPR) Rate (time frame: At the time of surgery (up to 15 weeks)). 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 NCT05908786.

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 15 Sep 2026.

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