A Study of Amivantamab Monotherapy in Participants With Previously Treated Advanced Hepatocellular Carcinoma
- Registration Number
- NCT05653427
- Lead Sponsor
- Janssen Research & Development, LLC
- Brief Summary
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)
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 18
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Amivantamab Monotherapy Amivantamab 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.
- Primary Outcome Measures
Name Time Method Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 by Investigator Assessment From start of treatment on Day 1 up to 3.8 months 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.
- Secondary Outcome Measures
Name Time Method Duration of Response (DOR) as Per RECIST Version 1.1 From the date of first documented response up to date of first documented PD or death (up to 3.8 months) 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.
Disease Control Rate (DCR) as Per RECIST Version 1.1 From start of treatment on Day 1 up to 3.8 months 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.
Progression Free Survival (PFS) as Per RECIST Version 1.1 From start of the treatment (Day 1) until disease progression or death (up to 3.8 months) 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.
Overall Survival (OS) From start of the treatment (Day 1) until death due to any cause (up to 3.8 months) OS was defined as the time from the date of first dose of study drug until the date of death due to any cause.
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 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) 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.
Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters 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 (serum chemistry and hematology) were reported. Clinically significant abnormalities were determined based on investigator's discretion.
Number of Participants With Clinically Significant Abnormalities in Vital Signs Values 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) 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.
Maximum Observed Serum Concentration (Cmax) of Amivantamab 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) 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.
Time to Reach Maximum Observed Serum Concentration (Tmax) of Amivantamab 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) 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.
Area Under the Serum Concentration Time Curve From Time Zero to Time 168 Hours (h) (AUC [0-168h]) of Amivantamab 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) 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.
Area Under the Serum Concentration Time Curve From Time Zero to End of Dosing Interval (AUCtau) of Amivantamab 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 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.
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 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) 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.
Serum Trough Concentrations (Ctrough) of Amivantamab: on Day 1 of Cycle 3 Pre-dose at 0 hour on Day 1 of Cycle 3 (each cycle was of 28 days) 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.
Terminal Elimination Half-Life (t1/2) of Amivantamab 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) 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.
Accumulation Ratio (AR) of AUC (0-168 h) of Amivantamab 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) 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.
Number of Participants With Anti-Amivantamab Antibodies From start of the treatment (Day 1) up to 30 days after the last dose of study drug (up to 3.8 months) Number of participants with anti-amivantamab antibodies were reported. Serum samples were assessed for anti-drug antibodies.
Trial Locations
- Locations (13)
The First Hospital of Jilin University
🇨🇳Chang Chun Shi, China
Beijing Cancer Hospital
🇨🇳Beijing, China
Zhejiang University First Hospital
🇨🇳Hang Zhou Shi, China
The Second Affiliatde Hospital To Nanchang University
🇨🇳Nan Chang Shi, China
The Third Xiangya Hospital, Central South University
🇨🇳Changsha, China
West China Hospital
🇨🇳Chengdu, China
Chongqing Cancer Hospital
🇨🇳Chong Qing, China
The Second Affiliated Hospital of Dalian Medical University
🇨🇳Dalian, China
Mengchao Hepatobiliary Hospital of Fujian Medical University
🇨🇳Fu Zhou Shi, China
Nanfang Hospital
🇨🇳Guang Zhou Shi, China
Zhejiang Cancer Hospital
🇨🇳Hangzhou, China
Xi An International Medical Center Hospital
🇨🇳XI An, China
Union Hospital Tongji Medical College of Huazhong University of Science and Technology
🇨🇳Wuhan, China