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

About

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.

Primary Purpose

Treatment

Study Type

Interventional

Phase

Phase 1/Phase 2

Eligibility

Gender

All

Healthy Volunteers

No

Minimum Age

18 Years

Maximum Age

N/A

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