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

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

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)

Study Overview

• Status: Terminated
• Conditions: Carcinoma, Hepatocellular
• Intervention / Treatment: Drug: Amivantamab

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100142
    • Beijing Cancer Hospital
  • Chang Chun Shi, China, 130021
    • The First Hospital of Jilin University
  • Changsha, China, 410013
    • The Third Xiangya Hospital, Central South University
  • Chengdu, China, 610041
    • West China Hospital
  • Chong Qing, China, 400033
    • Chongqing Cancer Hospital
  • Dalian, China, 116023
    • The Second Affiliated Hospital of Dalian Medical University
  • Fu Zhou Shi, China, 350025
    • Mengchao Hepatobiliary Hospital OF Fujian Medical University
  • Guang Zhou Shi, China, 510515
    • Nanfang Hospital
  • Hang Zhou Shi, China, 310003
    • Zhejiang University First Hospital
  • Hangzhou, China, 310022
    • Zhejiang Cancer Hospital
  • Nan Chang Shi, China, 330030
    • The Second Affiliatde Hospital To Nanchang University
  • Wuhan, China, 430030
    • Union Hospital Tongji Medical College of Huazhong University of Science and Technology
  • XI An, China, 710100
    • Xi An International Medical Center Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Amivantamab Monotherapy; 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; Amivantamab will be administered intravenously.; Other Names: JNJ-61186372

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 by Investigator Assessment	ORR was defined as the percentage of participants who achieved a confirmed complete response (CR) or partial response (PR) as determined by investigator per RECIST version 1.1. As per RECIST version 1.1, CR was defined as disappearance of all extranodal lesions, the regression of all nodal lesions to less than (<)10 millimeter (mm) short axis and the normalization of tumor marker level. PR was defined as greater than or equal to (>=) 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference baseline sum of diameters of target lesions.	From start of treatment on Day 1 up to 3.8 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response (DOR) as Per RECIST Version 1.1	DOR was defined as time from date of first documented response (CR/PR) until date of first documented progressive disease (PD) or death, whichever occurred first. As per RECIST version 1.1, CR was defined as disappearance of all extranodal lesions, the regression of all nodal lesions to <10 mm short axis and the normalization of tumor marker level. PR was defined as >=30% decrease in the sum of diameters of target lesions, taking as reference baseline sum of diameters of target lesions. PD was defined as an increase of at least 20% in the sum of the diameters of target lesions, taking as reference the smallest sum of the diameters of target lesions recorded since treatment started. There was no participant who had event (CR/PR), hence data could not be collected and analyzed for this outcome measure.	From the date of first documented response up to date of first documented PD or death (up to 3.8 months)
Disease Control Rate (DCR) as Per RECIST Version 1.1	DCR was defined as the percentage of participants achieving CR or PR or stable disease (SD) for at least 11 weeks as defined by RECIST version 1.1. As per RECIST version 1.1, CR was defined as disappearance of all extranodal lesions, the regression of all nodal lesions to <10 mm short axis and the normalization of tumor marker level. PR was defined as >=30% decrease in the sum of diameters of target lesions, taking as reference baseline sum of diameters of target lesions. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD). PD was defined as an increase of at least 20% in the sum of the diameters of target lesions, taking as reference the smallest sum of the diameters of target lesions recorded since treatment started.	From start of treatment on Day 1 up to 3.8 months
Progression Free Survival (PFS) as Per RECIST Version 1.1	PFS was defined as the time from the date of first dose of study drug until the date of objective disease progression or death by any cause, whichever comes first, based on investigator assessment using RECIST Version 1.1. PD was defined as an increase of at least 20% in the sum of the diameters of target lesions, taking as reference the smallest sum of the diameters of target lesions recorded since treatment started.	From start of the treatment (Day 1) until disease progression or death (up to 3.8 months)
Overall Survival (OS)	OS was defined as the time from the date of first dose of study drug until the date of death due to any cause.	From start of the treatment (Day 1) until death due to any cause (up to 3.8 months)
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0	An adverse event (AE) was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. TEAEs was defined as AEs occurring at or after first dose of study drug up to 30 days after last dose or until the start of new anticancer therapy, whichever occurred first. TEAEs were graded according to NCI-CTCAE version 5.0. Grade 1- Mild; Grade 2- Moderate; Grade 3- Severe or medically significant but not immediately life-threatening; Grade 4- Life-threatening consequences; Grade 5- Death related to AE. All TEAEs including serious and non-serious events were reported in this outcome measure.	From start of the treatment (Day 1) up to 30 days after last dose of study drug or start of subsequent anticancer therapy (up to 3.8 months)
Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters	Number of participants with clinically significant abnormalities in laboratory parameters (serum chemistry and hematology) were reported. Clinically significant abnormalities were determined based on investigator's discretion.	From start of the treatment (Day 1) up to 30 days after last dose of study drug or start of subsequent anticancer therapy (up to 3.8 months)
Number of Participants With Clinically Significant Abnormalities in Vital Signs Values	Vital signs assessments included systolic and diastolic blood pressure, heart rate, respiratory rate, pulse rate, body temperature and oxygen saturation. These measurements were taken after the participants had rested for at least 5 minutes in a quiet setting without distractions. Clinical significance of any vital signs was determined based on investigator's discretion.	From start of the treatment (Day 1) up to 30 days after last dose of study drug or start of subsequent anticancer therapy (up to 3.8 months)
Maximum Observed Serum Concentration (Cmax) of Amivantamab	Cmax was defined as the maximum observed serum concentration of amivantamab. The concentrations of amivantamab were measured using a validated, specific, and sensitive enzyme-linked immunosorbent assay (ELISA) method.	Pre-dose, 0, 24, 26, 30, 48, 96 and 168 hours post-dose on Day 1 of Cycle 1; pre-dose, 0, 2, 6, 24, 72, 168, 240 and 336 hours post-dose on Day 1 of Cycle 2 (each cycle was of 28 days)
Time to Reach Maximum Observed Serum Concentration (Tmax) of Amivantamab	Tmax was defined as the time to reach maximum observed serum concentration of amivantamab. The concentrations of amivantamab were measured using a validated, specific, and sensitive ELISA method.	Pre-dose, 0, 24, 26, 30, 48, 96 and 168 hours post-dose on Day 1 of Cycle 1; pre-dose, 0, 2, 6, 24, 72, 168, 240 and 336 hours post-dose on Day 1 of Cycle 2 (each cycle was of 28 days)
Area Under the Serum Concentration Time Curve From Time Zero to Time 168 Hours (h) (AUC [0-168h]) of Amivantamab	AUC (0-168h) was defined as area under the serum concentration time-curve from time zero to the time point 168 hours. The concentrations of amivantamab were measured using a validated, specific, and sensitive ELISA method.	Pre-dose, 0, 24, 26, 30, 48, 96 and 168 hours post-dose on Day 1 of Cycle 1; pre-dose, 0, 2, 6, 24, 72 and 168 hours post-dose on Day 1 of Cycle 2 (each cycle was of 28 days)
Area Under the Serum Concentration Time Curve From Time Zero to End of Dosing Interval (AUCtau) of Amivantamab	Area under the serum concentration curve from time 0 to end of dosing interval (AUCtau), where dosing interval of 336 hours was reported. The concentrations of amivantamab were measured using a validated, specific, and sensitive ELISA method.	Pre-dose, 0, 2, 6, 24, 72, 168, 240 and 336 hours post-dose on Day 1 of Cycle 2 (each cycle was of 28 days)
Serum Trough Concentrations (Ctrough) of Amivantamab: on Days 8 and 15 of Cycle 1; Day 1 of Cycle 2 and Cycle 4; Day 15 of Cycle 2 and Cycle 3	Ctrough of amivantamab at pre-dose on Days 8 and 15 of Cycle 1; Day 1 of Cycle 2 and Cycle 4; Day 15 of Cycle 2 and Cycle 3 were reported. Ctrough was defined as pre-dose serum drug concentration. The concentrations of amivantamab were measured using a validated, specific, and sensitive ELISA method.	Pre-dose at 0 hour: Days 8 and 15 of Cycle 1; Day 1 of Cycle 2 and Cycle 4; Day 15 of Cycle 2 and Cycle 3 (each cycle was of 28 days)
Serum Trough Concentrations (Ctrough) of Amivantamab: on Day 1 of Cycle 3	Ctrough of amivantamab at pre-dose on Day 1 of Cycle 3 were reported. Ctrough was defined as pre-dose serum drug concentration. The concentrations of amivantamab were measured using a validated, specific, and sensitive ELISA method. As per change in planned analysis, data was not summarized for timepoint where number of participants analyzed were less than 3. Only individual participant data was available and reported.	Pre-dose at 0 hour on Day 1 of Cycle 3 (each cycle was of 28 days)
Terminal Elimination Half-Life (t1/2) of Amivantamab	Terminal elimination half-life (t1/2) was the time measured for the serum concentration of a drug to decrease by half of its initial concentration. The concentrations of amivantamab were measured using a validated, specific, and sensitive ELISA method.	Pre-dose, 0, 2, 6, 24, 72, 168, 240 and 336 hours post-dose on Day 1 of Cycle 2 (each cycle was of 28 days)
Accumulation Ratio (AR) of AUC (0-168 h) of Amivantamab	Accumulation ratio for AUC was calculated as AUC (0-168 h) for Cycle 2 Day 1 divided by AUC (0-168 h) for Cycle 1 Day 1. The concentrations of amivantamab were measured using a validated, specific, and sensitive ELISA method.	Pre-dose, 0, 24, 26, 30, 48, 96 and 168 hours post-dose on Day 1 of Cycle 1; pre-dose, 0, 2, 6, 24, 72 and 168 hours post-dose on Day 1 of Cycle 2 (each cycle was of 28 days)
Number of Participants With Anti-Amivantamab Antibodies	Number of participants with anti-amivantamab antibodies were reported. Serum samples were assessed for anti-drug antibodies.	From start of the treatment (Day 1) up to 30 days after the last dose of study drug (up to 3.8 months)

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Investigators: Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (Actual): December 8, 2022
• Primary Completion (Actual): October 10, 2023
• Study Completion (Actual): October 10, 2023

Study Registration Dates

• First Submitted: December 8, 2022
• First Submitted That Met QC Criteria: December 8, 2022
• First Posted (Actual): December 16, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 9, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Antineoplastic Agents, Immunological; Antineoplastic Agents; Amivantamab-vmjw
• Other Study ID Numbers: CR109249; 61186372HCC2001 (Other Identifier: Janssen Research & Development, LLC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale open Data Access (YODA) Project site at yoda.yale.edu

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes