Safety and Efficacy of Coformulated Pembrolizumab/Quavonlimab (MK-1308A) in Combination With Lenvatinib (E7080/MK-7902) in Advanced Hepatocellular Carcinoma (MK-1308A-004)

Inclusion Criteria:

• Has an HCC diagnosis confirmed by radiology, histology, or cytology (fibrolamellarand mixed hepatocellular/cholangiocarcinoma subtypes are not eligible)

• Has Barcelona Clinic Liver Cancer (BCLC) Stage C disease, or BCLC Stage B diseasenot amenable to locoregional therapy or refractory to locoregional therapy, and notamenable to a curative treatment approach

• Has a Child-Pugh class A liver score within 7 days prior to first dose of studyintervention.

• Has a predicted life expectancy of >3 months

• Has at least 1 measurable HCC lesion based on RECIST 1.1, confirmed by BICR

• Has an Eastern Cooperative Oncology Group Performance Score (ECOG PS) of 0 to 1within 7 days prior to first dose of study intervention.

• Participants with controlled hepatitis B will be eligible as long as they meet thefollowing criteria: antiviral therapy for Hepatitis B virus (HBV) must be given forat least 4 weeks and HBV viral load must be less than 500 IU/mL prior to first doseof study drug

• Has adequately controlled blood pressure with or without antihypertensivemedications

• Has adequate organ function.

Exclusion Criteria:

• Has had esophageal or gastric variceal bleeding within the last 6 months.

• Has bleeding or thrombotic disorders or use of factor X inhibitors or anticoagulantsrequiring therapeutic international normalized ratio (INR) monitoring, e.g.,warfarin or similar agents

• Has clinically apparent ascites on physical examination

• Has inferior vena cava or cardiac involvement of HCC based on imaging

• Has had clinically diagnosed hepatic encephalopathy in the last 6 monthsunresponsive to therapy

• Has medical contraindications that preclude all forms of contrast-enhanced imaging (computed tomography [CT] or magnetic resonance imaging [MRI])

• Has gastrointestinal malabsorption, gastrointestinal anastomosis, or any othercondition that might affect the absorption of lenvatinib

• Has a preexisting Grade ≥3 gastrointestinal or non-gastrointestinal fistula

• Has clinically active hemoptysis (bright red blood of a least 0.5 teaspoon) within 3weeks prior to the first dose of study drug

• Has clinically significant cardiovascular impairment within 12 months of the firstdose of study intervention, including New York Heart Association (NYHA) Class III orIV congestive heart failure, unstable angina, myocardial infarction, cerebralvascular accident, or cardiac arrhythmia associated with hemodynamic instability

• Has had major surgery to the liver within 4 weeks prior to the first dose of studyintervention

• Has had a minor surgery (i.e., simple excision) within 7 days prior to the firstdose of study intervention (Cycle 1 Day 1)

• Has serious nonhealing wound, ulcer, or bone fracture

• Has received any systemic chemotherapy, including anti- vascular endothelial growthfactor (VEGF) therapy, or any systemic investigational anticancer agents fortreatment of HCC

• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent orwith an agent directed to another stimulatory or coinhibitory T-cell receptor

• Has received locoregional therapy to liver within 4 weeks prior to the first dose ofstudy intervention

• Has received prior radiotherapy to a non-liver region within 2 weeks of start ofstudy intervention

• Has received a live or live-attenuated vaccine within 30 days before the first doseof study drug

• Is currently participating in or has participated in a study of an investigationalagent or has used an investigational device within 4 weeks prior to the first doseof study intervention

• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapyor any other form of immunosuppressive therapy within 7 days prior the first dose ofstudy intervention

• Has a known additional malignancy that is progressing or has required activetreatment within the past 3 years

• Has a known history of, or any evidence of, central nervous system (CNS) metastasesand/or carcinomatous meningitis as assessed by local site investigator

• Has severe hypersensitivity (≥Grade 3) to study intervention and/or any of theirexcipients

• Has an active autoimmune disease that has required systemic treatment in past 2years

• Has a history of (noninfectious) pneumonitis/interstitial lung disease that requiredsteroids or has current pneumonitis/interstitial lung disease

• Has an active infection requiring systemic therapy, with the exception of HBV orHepatitis C virus (HCV)

• Has a known history of human immunodeficiency virus (HIV) infection

• Has dual active HBV infection (HBsAg (+) and /or detectable HBV DNA) and HCVinfection (anti-HCV antibody [Ab] positive and detectable HCV RNA) at study entry

• Has a history or current evidence of any condition, therapy, or laboratoryabnormality that might confound the results of the study, interfere with the

• Has inferior vena cava or cardiac involvement of HCC based on imaging
 

• Has had clinically diagnosed hepatic encephalopathy in the last 6 months
unresponsive to therapy
 

• Has medical contraindications that preclude all forms of contrast-enhanced imaging
 (computed tomography [CT] or magnetic resonance imaging [MRI])
 

• Has gastrointestinal malabsorption, gastrointestinal anastomosis, or any other
condition that might affect the absorption of lenvatinib
 

• Has a preexisting Grade ≥3 gastrointestinal or non-gastrointestinal fistula
 

• Has clinically active hemoptysis (bright red blood of a least 0.5 teaspoon) within 3
weeks prior to the first dose of study drug
 

• Has clinically significant cardiovascular impairment within 12 months of the first
dose of study intervention, including New York Heart Association (NYHA) Class III or
IV congestive heart failure, unstable angina, myocardial infarction, cerebral
vascular accident, or cardiac arrhythmia associated with hemodynamic instability
 

• Has had major surgery to the liver within 4 weeks prior to the first dose of study
intervention
 

• Has had a minor surgery (i.e., simple excision) within 7 days prior to the first
dose of study intervention (Cycle 1 Day 1)
 

• Has serious nonhealing wound, ulcer, or bone fracture
 

• Has received any systemic chemotherapy, including anti- vascular endothelial growth
factor (VEGF) therapy, or any systemic investigational anticancer agents for
treatment of HCC
 

• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or
with an agent directed to another stimulatory or coinhibitory T-cell receptor
 

• Has received locoregional therapy to liver within 4 weeks prior to the first dose of
study intervention
 

• Has received prior radiotherapy to a non-liver region within 2 weeks of start of
study intervention
 

• Has received a live or live-attenuated vaccine within 30 days before the first dose
of study drug
 

• Is currently participating in or has participated in a study of an investigational
agent or has used an investigational device within 4 weeks prior to the first dose
of study intervention
 

• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
or any other form of immunosuppressive therapy within 7 days prior the first dose of
study intervention
 

• Has a known additional malignancy that is progressing or has required active
treatment within the past 3 years
 

• Has a known history of, or any evidence of, central nervous system (CNS) metastases
and/or carcinomatous meningitis as assessed by local site investigator
 

• Has severe hypersensitivity (≥Grade 3) to study intervention and/or any of their
excipients
 

• Has an active autoimmune disease that has required systemic treatment in past 2
years
 

• Has a history of (noninfectious) pneumonitis/interstitial lung disease that required
steroids or has current pneumonitis/interstitial lung disease
 

• Has an active infection requiring systemic therapy, with the exception of HBV or
Hepatitis C virus (HCV)
 

• Has a known history of human immunodeficiency virus (HIV) infection
 

• Has dual active HBV infection (HBsAg (+) and /or detectable HBV DNA) and HCV
infection (anti-HCV antibody [Ab] positive and detectable HCV RNA) at study entry
 

• Has a history or current evidence of any condition, therapy, or laboratory
abnormality that might confound the results of the study, interfere with the
participant's participation for the full duration of the study, or is not in thebest interest of the participant to participate, in the opinion of the treatinginvestigator

• Has a known psychiatric or substance abuse disorder that would interfere with theparticipants ability to cooperate with the requirements of the study

• Has had an allogenic tissue/solid organ transplant