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

Primary Purpose

Carcinoma, Hepatocellular

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Atezolizumab
Bevacizumab
Tiragolumab
Tobemstomig
Sponsored by
Hoffmann-La Roche
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Carcinoma, Hepatocellular

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 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

Sites / Locations

  • Georgetown University Medical CenterRecruiting
  • Barbara Ann Karmanos Cancer Institute - Karmanos Cancer Center - Main CampusRecruiting
  • Severance Hospital, Yonsei University Health SystemRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Atezo + Bev

Atezo + Bev +Tira

Tobe + Bev

Arm Description

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.

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.

Participants in the Tobemstomig + Bev arm will receive up to three cycles of treatment until surgery or unacceptable toxicity, whichever occurs first.

Outcomes

Primary Outcome Measures

Major Pathologic Response (MPR) Rate
MPR rate is defined as the proportion of resected participants with an MPR =<10% (residual viable tumor in the tumor bed), as assessed by central review.

Secondary Outcome Measures

Pathologic Complete Response (pCR) Rate
pCR rate is defined as the proportion of resected participants with a pCR. pCR is defined as the absence of residual tumor in the resected tumor specimen.
Relapse-Free Survival (RFS)
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.
Event-Free Survival (EFS)
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 or distant disease recurrence as measured by EASL and/or RECIST v1.1; or death from any cause.
Overall Survival (OS)
OS is defined as the time from randomization to death from any cause.
Objective Response Rate (ORR)
ORR is defined as the proportion of participants with a Complete Response (CR) or Partial Response (PR), as determined by the investigator according to RECIST v1.1 and HCC mRECIST, prior to surgery. 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.
Proportion of Participants Downstaged to Within Milan Criteria
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.
R0 Resection Rate
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.
Percentage of Participants With Adverse Events
Proportion of Participants With Delayed or Canceled Surgery Due to Treatment-Related Adverse Events
Proportion of participants with delayed or canceled surgery due to treatment-related adverse events (defined as > 28 days from surgical restaging visit).
Post-Operative Surgical Complication Rates According to The Clavien-Dindo Surgical Classification
Post-operative surgical complication rates according to the Clavien-Dindo surgical classification. Clinically relevant complications are defined as Clavien-Dindo Grade >= IIIa.
Post-Operative Mortality
Post-operative mortality is defined as death within 90 days after surgery or prior to discharge.

Full Information

First Posted
June 7, 2023
Last Updated
October 19, 2023
Sponsor
Hoffmann-La Roche
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1. Study Identification

Unique Protocol Identification Number
NCT05908786
Brief Title
A Study Evaluating The Efficacy and Safety of Neoadjuvant Immunotherapy Combinations in Patients With Surgically Resectable Hepatocellular Carcinoma
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)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 31, 2023 (Anticipated)
Primary Completion Date
March 31, 2025 (Anticipated)
Study Completion Date
December 31, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carcinoma, Hepatocellular

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
150 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Atezo + Bev
Arm Type
Experimental
Arm Description
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.
Arm Title
Atezo + Bev +Tira
Arm Type
Experimental
Arm Description
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.
Arm Title
Tobe + Bev
Arm Type
Experimental
Arm Description
Participants in the Tobemstomig + Bev arm will receive up to three cycles of treatment until surgery or unacceptable toxicity, whichever occurs first.
Intervention Type
Drug
Intervention Name(s)
Atezolizumab
Other Intervention Name(s)
Tecentriq
Intervention Description
Atezolizumab will be administered at a dose of 1200 mg by IV infusion on Day 1.
Intervention Type
Drug
Intervention Name(s)
Bevacizumab
Other Intervention Name(s)
Avastin
Intervention Description
Bevacizumab will be administered at a dose of 15 mg/kg by IV infusion on Day 1.
Intervention Type
Drug
Intervention Name(s)
Tiragolumab
Intervention Description
Tiragolumab will be administered at a dose of 600 mg by IV infusion on Day 1.
Intervention Type
Drug
Intervention Name(s)
Tobemstomig
Other Intervention Name(s)
RO7247669
Intervention Description
Tobemstomig will be administered at a dose of 600 mg by IV infusion on Day 1
Primary Outcome Measure Information:
Title
Major Pathologic Response (MPR) Rate
Description
MPR rate is defined as the proportion of resected participants with an MPR =<10% (residual viable tumor in the tumor bed), as assessed by central review.
Time Frame
At the time of surgery
Secondary Outcome Measure Information:
Title
Pathologic Complete Response (pCR) Rate
Description
pCR rate is defined as the proportion of resected participants with a pCR. pCR is defined as the absence of residual tumor in the resected tumor specimen.
Time Frame
At the time of surgery
Title
Relapse-Free Survival (RFS)
Description
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.
Time Frame
Surgery to the first documented recurrence of disease (up to approximately 2 years)
Title
Event-Free Survival (EFS)
Description
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 or distant disease recurrence as measured by EASL and/or RECIST v1.1; or death from any cause.
Time Frame
Randomization up to approximately 3 years
Title
Overall Survival (OS)
Description
OS is defined as the time from randomization to death from any cause.
Time Frame
Randomization to death from any cause (up to approximately 3 years)
Title
Objective Response Rate (ORR)
Description
ORR is defined as the proportion of participants with a Complete Response (CR) or Partial Response (PR), as determined by the investigator according to RECIST v1.1 and HCC mRECIST, prior to surgery. 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.
Time Frame
Prior to surgery
Title
Proportion of Participants Downstaged to Within Milan Criteria
Description
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.
Time Frame
Prior to surgery
Title
R0 Resection Rate
Description
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.
Time Frame
At the time of surgery
Title
Percentage of Participants With Adverse Events
Time Frame
Up to approximately 3 years after first participant enrolled
Title
Proportion of Participants With Delayed or Canceled Surgery Due to Treatment-Related Adverse Events
Description
Proportion of participants with delayed or canceled surgery due to treatment-related adverse events (defined as > 28 days from surgical restaging visit).
Time Frame
>28 days from surgical restaging visit, anticipated up to 56 days
Title
Post-Operative Surgical Complication Rates According to The Clavien-Dindo Surgical Classification
Description
Post-operative surgical complication rates according to the Clavien-Dindo surgical classification. Clinically relevant complications are defined as Clavien-Dindo Grade >= IIIa.
Time Frame
Surgery to treatment completion/discontinuation (up to approximately 2 years)
Title
Post-Operative Mortality
Description
Post-operative mortality is defined as death within 90 days after surgery or prior to discharge.
Time Frame
Within 90 days after surgery or prior to discharge

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Reference Study ID Number: GO44457 https://forpatients.roche.com/
Phone
888-662-6728 (U.S. and Canada)
Email
global.rochegenentechtrials@roche.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
Georgetown University Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Individual Site Status
Recruiting
Facility Name
Barbara Ann Karmanos Cancer Institute - Karmanos Cancer Center - Main Campus
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201-2013
Country
United States
Individual Site Status
Recruiting
Facility Name
Severance Hospital, Yonsei University Health System
City
Seoul
ZIP/Postal Code
03722
Country
Korea, Republic of
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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).

Learn more about this trial

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

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