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

Carcinoma, Hepatocellular Clinical Trial

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05908786
• Other study ID #: GO44457
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: December 5, 2023
• Est. completion date: September 30, 2028

Study information

• Verified date: June 2024
• Source: Hoffmann-La Roche
• Contact: Reference Study ID Number: GO44457 https://forpatients.roche.com
• Phone: 888-662-6728 (U.S. and Canada)
• Email: global.rochegenentechtrials[@]roche.com
• Is FDA regulated: No
• Study type: Interventional

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: September 30, 2028
• Est. primary completion date: September 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular

Intervention

Drug:
• Atezolizumab
Atezolizumab will be administered at a dose of 1200 mg by IV infusion on Day 1.
• Bevacizumab
Bevacizumab will be administered at a dose of 15 mg/kg by IV infusion on Day 1.
• Tiragolumab
Tiragolumab will be administered at a dose of 600 mg by IV infusion on Day 1.
• Tobemstomig
Tobemstomig will be administered at a dose of 600 mg by IV infusion on Day 1

Locations

Country	Name	City	State
France	Centre Georges Francois Leclerc (CGFL)	Dijon
France	Centre Eugene Marquis (CEM)	Rennes
France	Assistance Publique-Hopitaux de Paris	Villejuif
France	Gustave Roussy	Villejuif
Germany	Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz; Medizinische Klinik und Poliklinik	Mainz
Korea, Republic of	CHA Bundang Medical Center	Gyeonggi-do
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
New Zealand	Auckland District Health Board (ADHB); Auckland City Hospital (ACH)	Auckland
Spain	Hospital Clinic de Barcelona (Hospital Clinic i Provincial); Barcelona Clinic Liver Cancer (BCLC)	Barcelona
Spain	Hospital Universitario Fundacion Jimenez Diaz.	Madrid
Spain	Clínica Universidad de Navarra	Pamplona	Navarra
Spain	Hospital Universitario Marques de Valdecilla	Santander	Cantabria
Taiwan	Chang Gung Medical Foundation, Kaohsiung Chang Gung Memorial Hospital	Tainan
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	Taipei Veterans General Hospital	Taipei City
Taiwan	National Taiwan University Hospital (NTUH) - Cancer Research Center	Zhongzheng Dist.
United Kingdom	Belfast Health and Social Care Trust - Belfast City Hospital	Belfast
United Kingdom	Imperial College London - Imperial Centre for Translational and Experimental Medicine (ICTEM)	London
United States	Montefiore Einstein Cancer Center	Bronx	New York
United States	UT Southwestern Medical Center	Dallas	Texas
United States	Barbara Ann Karmanos Cancer Institute - Karmanos Cancer Center - Main Campus	Detroit	Michigan
United States	University of Southern California (USC); Norris Comprehensive Cancer Center	Los Angeles	California
United States	Yale School of Medicine - Smilow Cancer Hospital - Yale-New Haven Hospital Location	New Haven	Colorado
United States	Columbia University Medical Center; Herbert Irving Pavilion Location	New York	New York
United States	University of Pennsylvania - Abramson Cancer Center	Philadelphia	Pennsylvania
United States	University of California Los Angeles (UCLA) - Cancer Care - Santa Monica	Santa Monica	California
United States	Fred Hutchinson/University of Washington Cancer Consortium	Seattle	Washington
United States	Georgetown University Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  France,  Germany,  Korea, Republic of,  New Zealand,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Major Pathologic Response (MPR) Rate	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.	At the time of surgery
Secondary	Pathologic Complete Response (pCR) Rate	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.	At the time of surgery
Secondary	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.	Surgery to the first documented recurrence of disease (up to approximately 2 years)
Secondary	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 regional, or distant disease recurrence as measured by EASL and/or RECIST v1.1; or death from any cause.	Randomization up to approximately 3 years
Secondary	Overall Survival (OS)	OS is defined as the time from randomization to death from any cause.	Randomization to death from any cause (up to approximately 3 years)
Secondary	OS Rate at 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.	Randomization up to 24 months
Secondary	OS Rate at 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.	Randomization up to 36 months
Secondary	Objective Response Rate (ORR)	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.	Prior to surgery
Secondary	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.	Prior to surgery
Secondary	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.	At the time of surgery
Secondary	Percentage of Participants With Adverse Events		Up to approximately 3 years after first participant enrolled
Secondary	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).	>28 days from surgical restaging visit, anticipated up to 56 days
Secondary	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.	Surgery to treatment completion/discontinuation (up to approximately 2 years)
Secondary	Post-Operative Mortality	Post-operative mortality is defined as death within 90 days after surgery	Within 90 days after surgery