A Study of Amivantamab Monotherapy in Participants With Previously Treated Advanced Hepatocellular Carcinoma

Study Overview
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Brief Summary
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The purpose of this study is to characterize the preliminary antitumor activity of amivantamab at the recommended dose in participants with previously systemically treated hepatocellular carcinoma (HCC)

Official Title
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A Phase 2, Open-Label Study to Evaluate the Safety, Efficacy and Pharmacokinetics of Amivantamab Monotherapy in Participants With Previously Treated Advanced Hepatocellular Carcinoma

Conditions
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Carcinoma, Hepatocellular

Intervention / Treatment
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* Drug: Amivantamab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant must have histologically or cytologically confirmed diagnosis of hepatocellular carcinoma (HCC) (fibrolamellar and mixed hepatocellular / cholangiocarcinoma subtypes are not eligible) based on pathology report, who have 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 Participant must have measurable disease according to response criteria in solid tumors (RECIST) Version 1.1. Selected target lesions must meet 1 of 2 criteria: 1) not previously treated with local therapy or 2) within the field of prior local therapy but with documented subsequent progression as per RECIST v1.1 Participant must have Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 Participant must have adequate organ and bone marrow function A female participant must agree not to donate eggs (ova, oocytes) or freeze for future use for the purposes of assisted reproduction during the study and for a period of 6 months after receiving the last dose of study treatment. Female participants should consider preservation of eggs prior to study treatment as anti-cancer treatments may impair fertility Exclusion Criteria: Participants with prior liver transplant, history of hepatic encephalopathy, portal vein invasion at the main portal branch (Vp4), inferior vena cava, or cardiac involvement of HCC based on imaging, or any current moderate or severe ascites as measured by physical examination that requires active paracentesis for control due to the underlying HCC Participant has known allergies, hypersensitivity, or intolerance to excipients of amivantamab Participant has received a live or live attenuated vaccine within 3 months before Cycle 1 Day 1. The seasonal influenza vaccine and non-live vaccines against Coronavirus disease 19 (COVID-19) are not exclusionary Other clinically active liver disease of infectious origin Participant has a history of clinically significant cardiovascular disease including, but not limited to: a. diagnosis of deep vein thrombosis or pulmonary embolism within 4 weeks prior to the first dose of study treatment or any of the following within 6 months prior to the first dose of study treatment: myocardial infarction, unstable angina, stroke, transient ischemic attack, coronary/peripheral artery bypass graft, or any acute coronary syndrome. Clinically non-significant thrombosis, such as nonobstructive catheter-associated clots, are not exclusionary; b. prolonged corrected QT interval using Fridericia's formula (QTcF) greater than (>)480 millisecond (msec) or clinically significant cardiac arrhythmia or electrophysiologic disease (example, placement of implantable cardioverter defibrillator or atrial fibrillation with uncontrolled rate); c. uncontrolled (persistent) hypertension: systolic blood pressure >160 mm Hg; diastolic blood pressure >100 millimeter of mercury (mm Hg), or congestive heart failure (CHF) defined as New York Heart Association (NYHA) class III/IV or hospitalization for CHF (any NYHA class) within 6 months of study enrollment; d. pericarditis/clinically significant pericardial effusion; e. myocarditis

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Amivantamab Monotherapy<br>Participants will receive amivantamab monotherapy intravenously once weekly on Days 1 and 2 in Cycle 1 and on Days 1 and 15 from Cycle 2 onwards based on body weight. Each cycle is of 28 days. | Drug: Amivantamab<br>* Amivantamab will be administered intravenously.<br>* Other names: JNJ-61186372;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | ORR is defined as the percentage of participants who achieve either partial response (PR) or complete response (CR), determined by investigator assessment using response criteria in solid tumors (RECIST) Version 1.1. | Up to 1 year 10 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Response (DOR) | DoR is defined as the time from the date of first documented response (CR or PR) until the date of documented progression or death, whichever comes first. | Up to 1 year 10 months | 
| Disease Control Rate (DCR) | DCR is defined as the percentage of participants achieving complete or partial response or stable disease of at least 11 weeks as defined by RECIST Version 1.1. | Up to 1 year 10 months | 
| Progression-free Survival (PFS) | PFS is defined as the time from the date the first dose until the date of objective disease progression or death by any cause, whichever comes first, based on investigator review according to RECIST Version 1.1. | Up to 1 year 10 months | 
| Overall Survival (OS) | OS is defined as the time from the date of the first dose until the date of death due to any cause. | Up to 1 year 10 months | 
| Number of Participants with of Adverse Events | An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Severity of AEs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event. | Up to 1 year 10 months | 
| Number of Participants with Abnormalities in Clinical Laboratory Assessments | Number of participants with abnormalities in clinical laboratory tests including serum chemistry and hematology) will be reported. | Up to 1 year 10 months | 
| Number of Participants with Abnormalities in Vital Signs | Number of participants with abnormalities in vital signs (including temperature, pulse/heart rate, and blood pressure) will be reported. | Up to 1 year 10 months | 
| Maximum Serum Concentration (Cmax) of Amivantamab | Cmax is defined as maximum serum concentration of amivantamab. | Up to 1 year 10 months | 
| Time to Reach Maximum Serum Concentration (Tmax) of Amivantamab | Tmax is defined as time to reach maximum serum concentration of amivantamab. | Up to 1 year 10 months | 
| Area Under the Serum Concentration-time Curve of Amivantamab from Time t1 to t2 (AUC[t1-t2]) | AUC(t1-t2) is defined as the area under the serum concentration-time curve of amivantamab from time t1 to t2. | Up to 1 year 10 months | 
| Area Under the Concentration-time Curve of Amivantamab From Time Zero to End of Dosing Interval (AUCtau) | AUCtau is the measure of the serum drug concentration of amivantamab from time zero to end of dosing interval. | Up to 1 year 10 months | 
| Serum Concentration Immediately Prior to the Next Dose Administration (Ctrough) of Amivantamab | Ctrough is defined as serum concentration immediately prior to the next dose administration (Ctrough) of amivantamab. | Up to 1 year 10 months | 
| Accumulation Ratio (R) | R is calculated as area under the plasma concentration-time curve from time zero to 24 hours (AUC [0-24]) value at steady state divided by AUC (0-24) value after first dose. | Up to 1 year 10 months | 
| Number of Participants with Anti-amivantamab Antibodies | Number of participants with anti-amivantamab antibodies will be reported. | Up to 1 year 10 months |