Carcinoma, Hepatocellular
Conditions
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)
Interventions
DRUGAmivantamab
Amivantamab will be administered intravenously.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
Countries
China
Participant flow
Pre-assignment details
The study was planned to be conducted in 3 parts: Part 1, main Part 2 and expansion Part 3. However, due to the early termination of study, the enrollment was discontinued before planned enrollment was achieved in Part 2. Due to changes in the planned analysis, efficacy and safety data were analyzed together for Part 1 and Part 2 and Part 3 was not conducted. As a result, combined results for both parts were presented.
Participants by arm
| Arm | Count |
|---|---|
| Amivantamab Monotherapy (1050/1400 mg) Participants with previously treated advanced hepatocellular carcinoma (HCC) received amivantamab 1050 milligrams (mg) for body weight less than (\<) 80 kilograms (kg) or 1400 mg for body weight greater than or equal to (\>=) 80 kg as an intravenous (IV) infusion in each 28-day cycles. During Cycle 1, amivantamab was administered once weekly on Days 1, 8, 15 and 22 with first dose split over Day 1 (350 mg) and Day 2 (700 mg for body weight \<80 kg/1050 mg for body weight \>=80 kg). From Cycle 2 onwards, amivantamab was administered on Days 1 and 15 until documented clinical or radiographic disease progression or until the participant discontinued study treatment due to withdrawal of consent, safety reasons, noncompliance with study drug administration or procedural requirements with treatment continuing for a maximum of up to 2.8 months. Participants were followed up for safety every 12 weeks after the last dose of study treatment or disease progression until the end of study, death, lost to follow-up, or withdrawal of consent, whichever comes first. | 18 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Study Terminated by Sponsor | 13 |
Baseline characteristics
| Characteristic | Amivantamab Monotherapy (1050/1400 mg) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 3 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants |
| Age, Continuous | 49.9 Years STANDARD_DEVIATION 12 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 18 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Region of Enrollment CHINA | 18 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 5 / 18 |
| other Total, other adverse events | 18 / 18 |
| serious Total, serious adverse events | 4 / 18 |
Outcome results
Primary
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.
Time frame: From start of treatment on Day 1 up to 3.8 months
Population: Response evaluable analysis set included all participants who received at least 1 dose of study treatment; had at least 1 post-baseline efficacy disease assessment, or discontinued treatment for any reason, or had disease progression/death prior to the first post-baseline disease assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Amivantamab Monotherapy (1050/1400 mg) | Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 by Investigator Assessment | 0.0 Percentage of participants |
Secondary
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.
Time frame: 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)
Population: PK analysis set included all participants who received at least 1 dose of study treatment and had at least 1 evaluable postbaseline measurement. Here 'N' (overall number of participants analyzed) refers to the participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Amivantamab Monotherapy (1050/1400 mg) | Accumulation Ratio (AR) of AUC (0-168 h) of Amivantamab | 2.85 Ratio | Standard Deviation 0.46 |
Secondary
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.
Time frame: 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)
Population: PK analysis set included all participants who received at least 1 dose of study treatment and had at least 1 evaluable postbaseline measurement. Here 'N' (overall number of participants analyzed) refers to the participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Amivantamab Monotherapy (1050/1400 mg) | Area Under the Serum Concentration Time Curve From Time Zero to End of Dosing Interval (AUCtau) of Amivantamab | 117913 mcg*hr/mL | Standard Deviation 19426 |
Secondary
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.
Time frame: 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)
Population: PK analysis set included all participants who received at least 1 dose of study treatment and had at least 1 evaluable postbaseline measurement. Here 'N' (overall number of participants analyzed) refers to the participants evaluable for this outcome measure and 'n' (number analyzed) refers to the participants evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Amivantamab Monotherapy (1050/1400 mg) | Area Under the Serum Concentration Time Curve From Time Zero to Time 168 Hours (h) (AUC [0-168h]) of Amivantamab | Cycle 1 Day 1 | 29084 micrograms*hours/milliliter (mcg*hr/mL) | Standard Deviation 3772 |
| Amivantamab Monotherapy (1050/1400 mg) | Area Under the Serum Concentration Time Curve From Time Zero to Time 168 Hours (h) (AUC [0-168h]) of Amivantamab | Cycle 2 Day 1 | 80434 micrograms*hours/milliliter (mcg*hr/mL) | Standard Deviation 11319 |
Secondary
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.
Time frame: From start of treatment on Day 1 up to 3.8 months
Population: Response evaluable analysis set included all participants who received at least 1 dose of study treatment; had at least 1 post-baseline efficacy disease assessment, or discontinued treatment for any reason, or had disease progression/death prior to the first post-baseline disease assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Amivantamab Monotherapy (1050/1400 mg) | Disease Control Rate (DCR) as Per RECIST Version 1.1 | 0.0 Percentage of participants |
Secondary
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.
Time frame: From the date of first documented response up to date of first documented PD or death (up to 3.8 months)
Population: Response evaluable analysis set included all participants who received at least 1 dose of study treatment; had at least 1 post-baseline efficacy disease assessment, or discontinued treatment for any reason, or had disease progression/death prior to the first post-baseline disease assessment. Here 'N' (overall number of participants analyzed) refers to the number of participants evaluable for this outcome measure.
Secondary
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.
Time frame: 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)
Population: Pharmacokinetics (PK) analysis set included all participants who received at least 1 dose of study treatment and had at least 1 evaluable postbaseline measurement. Here 'N' (overall number of participants analyzed) refers to the participants evaluable for this outcome measure and 'n' (number analyzed) refers to the participants evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Amivantamab Monotherapy (1050/1400 mg) | Maximum Observed Serum Concentration (Cmax) of Amivantamab | Cycle 1 Day 1 | 339 Micrograms per milliliter (mcg/mL) | Standard Deviation 57 |
| Amivantamab Monotherapy (1050/1400 mg) | Maximum Observed Serum Concentration (Cmax) of Amivantamab | Cycle 2 Day 1 | 711 Micrograms per milliliter (mcg/mL) | Standard Deviation 79 |
Secondary
Number of Participants With Anti-Amivantamab Antibodies
Number of participants with anti-amivantamab antibodies were reported. Serum samples were assessed for anti-drug antibodies.
Time frame: From start of the treatment (Day 1) up to 30 days after the last dose of study drug (up to 3.8 months)
Population: Immunogenicity analysis set included all participants who received at least 1 dose of study treatment and had at least 1 evaluable postbaseline measurement. Here 'N' (overall number of participants analyzed) refers to the participants with appropriate samples had 1 or more samples obtained after their first amivantamab administration.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Amivantamab Monotherapy (1050/1400 mg) | Number of Participants With Anti-Amivantamab Antibodies | 0 Participants |
Secondary
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.
Time frame: 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)
Population: All treated analysis set included all participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Amivantamab Monotherapy (1050/1400 mg) | Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters | 3 Participants |
Secondary
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.
Time frame: 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)
Population: All treated analysis set included all participants who received at least 1 dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Amivantamab Monotherapy (1050/1400 mg) | Number of Participants With Clinically Significant Abnormalities in Vital Signs Values | 0 Participants |
Secondary
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.
Time frame: 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)
Population: All treated analysis set included all participants who received at least 1 dose of study treatment.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Amivantamab Monotherapy (1050/1400 mg) | 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 | Grade 1 | 5 Participants |
| Amivantamab Monotherapy (1050/1400 mg) | 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 | Grade 2 | 9 Participants |
| Amivantamab Monotherapy (1050/1400 mg) | 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 | Grade 3 | 3 Participants |
| Amivantamab Monotherapy (1050/1400 mg) | 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 | Grade 4 | 0 Participants |
| Amivantamab Monotherapy (1050/1400 mg) | 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 | Grade 5 | 1 Participants |
Secondary
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.
Time frame: From start of the treatment (Day 1) until death due to any cause (up to 3.8 months)
Population: Response evaluable analysis set included all participants who received at least 1 dose of study treatment; had at least 1 post-baseline efficacy disease assessment, or discontinued treatment for any reason, or had disease progression/death prior to the first post-baseline disease assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Amivantamab Monotherapy (1050/1400 mg) | Overall Survival (OS) | NA Months |
Secondary
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.
Time frame: From start of the treatment (Day 1) until disease progression or death (up to 3.8 months)
Population: Response evaluable analysis set included all participants who received at least 1 dose of study treatment; had at least 1 post-baseline efficacy disease assessment, or discontinued treatment for any reason, or had disease progression/death prior to the first post-baseline disease assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Amivantamab Monotherapy (1050/1400 mg) | Progression Free Survival (PFS) as Per RECIST Version 1.1 | 1.48 Months |
Secondary
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.
Time frame: Pre-dose at 0 hour on Day 1 of Cycle 3 (each cycle was of 28 days)
Population: PK analysis set included all participants who received at least 1 dose of study treatment and had at least 1 evaluable postbaseline measurement. Here 'N' (overall number of participants analyzed) refers to the participants evaluable for this outcome measure and 'n' (number analyzed) refers to the participants evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Amivantamab Monotherapy (1050/1400 mg) | Serum Trough Concentrations (Ctrough) of Amivantamab: on Day 1 of Cycle 3 | Participant 1 | 104 mcg/mL |
| Amivantamab Monotherapy (1050/1400 mg) | Serum Trough Concentrations (Ctrough) of Amivantamab: on Day 1 of Cycle 3 | Participant 2 | 162 mcg/mL |
Secondary
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.
Time frame: 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)
Population: PK analysis set included all participants who received at least 1 dose of study treatment and had at least 1 evaluable postbaseline measurement. Here 'N' (overall number of participants analyzed) refers to the participants evaluable for this outcome measure and 'n' (number analyzed) refers to the participants evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Amivantamab Monotherapy (1050/1400 mg) | 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 Cycle 1 Day 8 | 145 mcg/mL | Standard Deviation 103 |
| Amivantamab Monotherapy (1050/1400 mg) | 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 Cycle 1 Day 15 | 229 mcg/mL | Standard Deviation 117 |
| Amivantamab Monotherapy (1050/1400 mg) | 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 Cycle 2 Day 1 | 326 mcg/mL | Standard Deviation 76 |
| Amivantamab Monotherapy (1050/1400 mg) | 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 Cycle 2 Day 15 | 216 mcg/mL | Standard Deviation 71.3 |
| Amivantamab Monotherapy (1050/1400 mg) | 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 Cycle 3 Day 15 | 87.7 mcg/mL | — |
| Amivantamab Monotherapy (1050/1400 mg) | 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 Cycle 4 Day 1 | 87.6 mcg/mL | — |
Secondary
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.
Time frame: 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)
Population: PK analysis set included all participants who received at least 1 dose of study treatment and had at least 1 evaluable postbaseline measurement. Here 'N' (overall number of participants analyzed) refers to the participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Amivantamab Monotherapy (1050/1400 mg) | Terminal Elimination Half-Life (t1/2) of Amivantamab | 201.3 Hours | Standard Deviation 39.8 |
Secondary
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.
Time frame: 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)
Population: PK analysis set included all participants who received at least 1 dose of study treatment and had at least 1 evaluable postbaseline measurement. Here 'N' (overall number of participants analyzed) refers to the participants evaluable for this outcome measure and 'n' (number analyzed) refers to the participants evaluable at specified time points.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Amivantamab Monotherapy (1050/1400 mg) | Time to Reach Maximum Observed Serum Concentration (Tmax) of Amivantamab | Cycle 1 Day 1 | 27.18 Hours |
| Amivantamab Monotherapy (1050/1400 mg) | Time to Reach Maximum Observed Serum Concentration (Tmax) of Amivantamab | Cycle 2 Day 1 | 5.87 Hours |