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

Janssen Research & Development, LLC13 sites in 1 country18 target enrollmentDecember 8, 2022

ConditionsCarcinoma, Hepatocellular

InterventionsAmivantamab

DrugsAmivantamab

Overview

Phase: Phase 2
Intervention: Amivantamab
Conditions: Carcinoma, Hepatocellular
Sponsor: Janssen Research & Development, LLC
Enrollment: 18
Locations: 13
Primary Endpoint: Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 by Investigator Assessment
Status: Terminated
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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)

Registry

clinicaltrials.gov

Start Date

December 8, 2022

End Date

October 10, 2023

Last Updated

last year

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

Janssen Research & Development, LLC

Responsible Party

Sponsor

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.
•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
•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

Arms & Interventions

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.

Intervention: Amivantamab

Outcomes

Primary Outcomes

Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 by Investigator Assessment

Time Frame: 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 Outcomes

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))
Disease Control Rate (DCR) as Per RECIST Version 1.1(From start of treatment on Day 1 up to 3.8 months)
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))
Overall Survival (OS)(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(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(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(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(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(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(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(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(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(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(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(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(From start of the treatment (Day 1) up to 30 days after the last dose of study drug (up to 3.8 months))