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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05908786
Recruitment Status : Recruiting
First Posted : June 18, 2023
Last Update Posted : May 20, 2024
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief 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 clinical activity or unacceptable toxicity, or modify the participant population.

Condition or disease Intervention/treatment Phase
Carcinoma, Hepatocellular Drug: Atezolizumab Drug: Bevacizumab Drug: Tiragolumab Drug: Tobemstomig Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : December 5, 2023
Estimated Primary Completion Date : September 30, 2025
Estimated Study Completion Date : September 30, 2028

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Atezo + Bev
Participants in the atezolizumab plus bevacizumab (Atezo + Bev) arm will receive up to three cycles of treatment until surgery or unacceptable toxicity, whichever occurs first.
Drug: Atezolizumab
Atezolizumab will be administered at a dose of 1200 mg by IV infusion on Day 1.
Other Name: Tecentriq

Drug: Bevacizumab
Bevacizumab will be administered at a dose of 15 mg/kg by IV infusion on Day 1.
Other Name: Avastin

Experimental: Atezo + Bev +Tira
Participants 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.
Drug: Atezolizumab
Atezolizumab will be administered at a dose of 1200 mg by IV infusion on Day 1.
Other Name: Tecentriq

Drug: Bevacizumab
Bevacizumab will be administered at a dose of 15 mg/kg by IV infusion on Day 1.
Other Name: Avastin

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

Experimental: Tobe + Bev
Participants in the Tobemstomig + Bev arm will receive up to three cycles of treatment until surgery or unacceptable toxicity, whichever occurs first.
Drug: Bevacizumab
Bevacizumab will be administered at a dose of 15 mg/kg by IV infusion on Day 1.
Other Name: Avastin

Drug: Tobemstomig
Tobemstomig will be administered at a dose of 600 mg by IV infusion on Day 1
Other Name: RO7247669




Primary Outcome Measures :
  1. Major Pathologic Response (MPR) Rate [ Time Frame: At the time of surgery ]
    MPR rate is defined as the proportion of participants with =<10% residual viable tumor in the tumor bed at the time of surgery, as assessed by central pathological review.


Secondary Outcome Measures :
  1. Pathologic Complete Response (pCR) Rate [ Time Frame: At the time of surgery ]
    pCR rate is defined as the proportion of participants with an absence of residual tumor at the time of surgery, as assessed by central pathological review.

  2. Relapse-Free Survival (RFS) [ Time Frame: Surgery to the first documented recurrence of disease (up to approximately 2 years) ]
    RFS is defined as the time from surgery to the first documented recurrence of disease (intrahepatic or extrahepatic) according to EASL and/or RECIST v1.1, or death from any cause.

  3. Event-Free Survival (EFS) [ Time Frame: Randomization up to approximately 3 years ]
    EFS is defined as the time from randomization to any of the following events (whichever occurs first): disease progression that precludes surgery, as assessed by the investigator according RECIST v1.1; local regional, or distant disease recurrence as measured by EASL and/or RECIST v1.1; or death from any cause.

  4. Overall Survival (OS) [ Time Frame: Randomization to death from any cause (up to approximately 3 years) ]
    OS is defined as the time from randomization to death from any cause.

  5. OS Rate at 24 Months [ Time Frame: Randomization up to 24 months ]
    OS rate at 24 months is defined as the proportion of participants who have not experience death from any cause at 24 months after randomization.

  6. OS Rate at 36 Months [ Time Frame: Randomization up to 36 months ]
    OS rate at 36 months is defined as the proportion of participants who have not experience death from any cause at 36 months after randomization.

  7. Objective Response Rate (ORR) [ Time Frame: Prior to surgery ]
    ORR is defined as the proportion of participants with a radiographic Complete Response (CR) or Partial Response (PR) prior to surgery, as determined by the investigator according to RECIST v1.1 and HCC mRECIST. Responses will be assessed and determined according to RECIST v1.1 and HCC mRECIST but are not required to be confirmed by subsequent imaging assessments.

  8. Proportion of Participants Downstaged to Within Milan Criteria [ Time Frame: Prior to surgery ]
    Proportion of participants downstaged to within Milan criteria (for participants beyond criteria at randomization). Within Milan criteria is defined as single tumor <= 5 cm or 2 - 3 nodules all <= 3 cm.

  9. R0 Resection Rate [ Time Frame: At the time of surgery ]
    R0 resection rate (proportion of resected participants obtaining an R0 resection). R0 resection is defined as a microscopically margin-negative resection, in which no tumor (gross or microscopic) remains in the primary tumor bed.

  10. Percentage of Participants With Adverse Events [ Time Frame: Up to approximately 3 years after first participant enrolled ]
  11. Proportion of Participants With Delayed or Canceled Surgery Due to Treatment-Related Adverse Events [ Time Frame: >28 days from surgical restaging visit, anticipated up to 56 days ]
    Proportion of participants with delayed or canceled surgery due to treatment-related adverse events (defined as > 28 days from surgical restaging visit).

  12. Post-Operative Surgical Complication Rates According to The Clavien-Dindo Surgical Classification [ Time Frame: Surgery to treatment completion/discontinuation (up to approximately 2 years) ]
    Post-operative surgical complication rates according to the Clavien-Dindo surgical classification. Clinically relevant complications are defined as Clavien-Dindo Grade >= IIIa.

  13. Post-Operative Mortality [ Time Frame: Within 90 days after surgery ]
    Post-operative mortality is defined as death within 90 days after surgery



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05908786


Contacts
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Contact: Reference Study ID Number: GO44457 https://forpatients.roche.com/ 888-662-6728 (U.S. and Canada) global.rochegenentechtrials@roche.com

Locations
Show Show 28 study locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT05908786    
Other Study ID Numbers: GO44457
First Posted: June 18, 2023    Key Record Dates
Last Update Posted: May 20, 2024
Last Verified: May 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here ( https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Bevacizumab
Atezolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action