Clinical trial NCT05653427: A Study of Amivantamab Monotherapy in Participants With Previously Treated Advanced Hepatocellular Carcinoma
Official title: A Phase 2, Open-Label Study to Evaluate the Safety, Efficacy and Pharmacokinetics of Amivantamab Monotherapy in Participants With Previously Treated Advanced Hepatocellular Carcinoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Carcinoma, Hepatocellular
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2022-12-16
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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)


Eligibility criteria: 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

Primary outcomes:
measure: Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 by Investigator Assessment
timeFrame: From start of treatment on Day 1 up to 3.8 months
Secondary outcomes:
measure: Duration of Response (DOR) as Per RECIST Version 1.1
timeFrame: From the date of first documented response up to date of first documented PD or death (up to 3.8 months)
measure: Disease Control Rate (DCR) as Per RECIST Version 1.1
timeFrame: From start of treatment on Day 1 up to 3.8 months
measure: Progression Free Survival (PFS) as Per RECIST Version 1.1
timeFrame: From start of the treatment (Day 1) until disease progression or death (up to 3.8 months)
measure: Overall Survival (OS)
timeFrame: From start of the treatment (Day 1) until death due to any cause (up to 3.8 months)
measure: 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
timeFrame: 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)
measure: Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters
timeFrame: 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)
measure: Number of Participants With Clinically Significant Abnormalities in Vital Signs Values
timeFrame: 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)
measure: Maximum Observed Serum Concentration (Cmax) of Amivantamab
timeFrame: 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)
measure: Time to Reach Maximum Observed Serum Concentration (Tmax) of Amivantamab
timeFrame: 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)
measure: Area Under the Serum Concentration Time Curve From Time Zero to Time 168 Hours (h) (AUC [0-168h]) of Amivantamab
timeFrame: 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)
measure: Area Under the Serum Concentration Time Curve From Time Zero to End of Dosing Interval (AUCtau) of Amivantamab
timeFrame: 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)
measure: 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
timeFrame: 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)
measure: Serum Trough Concentrations (Ctrough) of Amivantamab: on Day 1 of Cycle 3
timeFrame: Pre-dose at 0 hour on Day 1 of Cycle 3 (each cycle was of 28 days)
measure: Terminal Elimination Half-Life (t1/2) of Amivantamab
timeFrame: 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)
measure: Accumulation Ratio (AR) of AUC (0-168 h) of Amivantamab
timeFrame: 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)
measure: Number of Participants With Anti-Amivantamab Antibodies
timeFrame: From start of the treatment (Day 1) up to 30 days after the last dose of study drug (up to 3.8 months)
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Chang Chun Shi
country: China
facility: The First Hospital of Jilin University
city: Changsha
country: China
facility: The Third Xiangya Hospital, Central South University
city: Chengdu
country: China
facility: West China Hospital
city: Chong Qing
country: China
facility: Chongqing Cancer Hospital
city: Dalian
country: China
facility: The Second Affiliated Hospital of Dalian Medical University
city: Fu Zhou Shi
country: China
facility: Mengchao Hepatobiliary Hospital of Fujian Medical University
city: Guang Zhou Shi
country: China
facility: Nanfang Hospital
city: Hang Zhou Shi
country: China
facility: Zhejiang University First Hospital
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
city: Nan Chang Shi
country: China
facility: The Second Affiliatde Hospital To Nanchang University
city: Wuhan
country: China
facility: Union Hospital Tongji Medical College of Huazhong University of Science and Technology
city: XI An
country: China
facility: Xi An International Medical Center Hospital
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical trial
role: STUDY_DIRECTOR
References: