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

Merck Sharp & Dohme LLC116 enrolled

Overview

The purpose of this study is to evaluate the safety and efficacy of fixed dose coformulated pembrolizumab/quavonlimab (MK-1308A) plus lenvatinib in a first line (1L) hepatocellular carcinoma (HCC) setting. No hypothesis testing will be performed.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

116

Conditions

Advanced Hepatocellular Carcinoma

Interventions

Pembrolizumab/QuavonlimabBIOLOGICAL

Pembrolizumab/Quavonlimab (400 mg/25 mg) administered via IV infusion Q6W.

LenvatinibDRUG

Lenvatinib 12 mg (body weight \[BW\] ≥60 kg) or 8 mg (BW \<60 kg) administered orally every day (QD).

PembrolizumabBIOLOGICAL

Pembrolizumab (400 mg) administered via IV infusion Q6W, in the event of intolerable toxicity to pembrolizumab/quavonlimab.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Has an HCC diagnosis confirmed by radiology, histology, or cytology (fibrolamellar and mixed hepatocellular/cholangiocarcinoma subtypes are not eligible) * Has Barcelona Clinic Liver Cancer (BCLC) Stage C disease, or BCLC Stage B disease not amenable to locoregional therapy or refractory to locoregional therapy, and not amenable to a curative treatment approach * Has a Child-Pugh class A liver score within 7 days prior to first dose of study intervention. * 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 1 within 7 days prior to first dose of study intervention. * Participants with controlled hepatitis B will be eligible as long as they meet the following criteria: antiviral therapy for Hepatitis B virus (HBV) must be given for at least 4 weeks and HBV viral load must be less than 500 IU/mL prior to first dose of study drug * Has adequately controlled blood pressure with or without antihypertensive medications * 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 anticoagulants requiring 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 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 the best interest of the participant to participate, in the opinion of the treating investigator * Has a known psychiatric or substance abuse disorder that would interfere with the participants ability to cooperate with the requirements of the study * Has had an allogenic tissue/solid organ transplant

Locations (40)

Outcomes

Primary Outcomes

Number of participants with a Dose-Limiting Toxicity (DLT) in the Safety Lead-in Phase

DLTs will be defined as follows unless determined to be unrelated to study intervention: any Grade 4 nonhematologic toxicity (not laboratory); any Grade 4 hematologic toxicity lasting \>7 days (Grade 4 lymphopenia lasting ≥21 days); Grade 3 platelet count decreased if associated with clinically significant hemorrhage; any Grade 3 nonhematologic toxicity (not laboratory) lasting \>3 days despite optimal supportive care; any clinically significant Grade 3 or Grade 4 nonhematologic laboratory abnormality if: medical intervention is required to treat participant, or abnormality leads to hospitalization, or abnormality persists for \>1 week (or bilirubin if persists \>4 weeks); aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) \>10.0 times upper limit of normal (ULN) or \>10.0 times baseline if baseline \>ULN; any febrile neutropenia Grade 3 or Grade 4; any treatment-related AE that causes the participant to discontinue study intervention during the DLT window; any Grade 5 toxicity

Time frame: Cycle 1 (Up to approximately 3 weeks)

Number of participants with ≥1 adverse event (AE)

An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants with an AE will be reported.

Time frame: Up to approximately 5 years

Number of participants with ≥1 serious adverse event (SAE)

An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is another important medical event. The number of participants with an SAE will be reported.

Time frame: Up to approximately 5 years

Number of participants with ≥1 immune-related AE (irAE)

Data from ClinicalTrials.gov

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Secondary Outcomes

Duration of Response (DOR) per RECIST 1.1 as assessed by BICR

For participants who demonstrate confirmed CR or PR per RECIST 1.1 assessed by BICR, DOR is defined as the time from the first documented evidence of CR (disappearance of all target lesions) or PR (at least a 30% decrease in the SOD of target lesions) until progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1 adjusted for this study to allow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, PD is defined as at least a 20% increase in the SOD of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD.