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)
Overview
- Phase
- Phase 1
- Intervention
- Atezolizumab
- Conditions
- Carcinoma, Hepatocellular
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 62
- Locations
- 30
- Primary Endpoint
- Major Pathologic Response (MPR) Rate
- Status
- Completed
- Last Updated
- 4 months ago
Overview
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.
Investigators
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
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
Arms & Interventions
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.
Intervention: Atezolizumab
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.
Intervention: Bevacizumab
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.
Intervention: Atezolizumab
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.
Intervention: Bevacizumab
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.
Intervention: Tiragolumab
Tobe + Bev
Participants in the Tobemstomig + Bev arm will receive up to three cycles of treatment until surgery or unacceptable toxicity, whichever occurs first. Enrollment is closed.
Intervention: Bevacizumab
Tobe + Bev
Participants in the Tobemstomig + Bev arm will receive up to three cycles of treatment until surgery or unacceptable toxicity, whichever occurs first. Enrollment is closed.
Intervention: Tobemstomig
Outcomes
Primary Outcomes
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 Outcomes
- Overall Survival (OS)(Randomization to death from any cause (up to approximately 3 years))
- Pathologic Complete Response (pCR) Rate(At the time of surgery)
- Proportion of Participants Downstaged to Within Milan Criteria(Prior to surgery)
- Post-Operative Mortality(Within 90 days after surgery)
- Percentage of Participants With Adverse Events(Up to approximately 3 years after first participant enrolled)
- Relapse-Free Survival (RFS)(Surgery to the first documented recurrence of disease (up to approximately 2 years))
- OS Rate at 24 Months(Randomization up to 24 months)
- R0 Resection Rate(At the time of surgery)
- Post-Operative Surgical Complication Rates According to The Clavien-Dindo Surgical Classification(Surgery to treatment completion/discontinuation (up to approximately 2 years))
- Event-Free Survival (EFS)(Randomization up to approximately 3 years)
- Objective Response Rate (ORR)(Prior to surgery)
- Proportion of Participants With Delayed or Canceled Surgery Due to Treatment-Related Adverse Events(>28 days from surgical restaging visit, anticipated up to 56 days)
- OS Rate at 36 Months(Randomization up to 36 months)