Esophageal Neoplasms, Stomach Neoplasms
Conditions
Brief summary
The purpose of this study is to investigate the activity of amivantamab in gastric cancer (GC) and esophageal cancer (EC) participants (Phase 2a), and to characterize the preliminary antitumor activity of amivantamab in selected GC and EC population (Phase 2b).
Interventions
DRUGAmivantamab
Amivantamab will be administered intravenously.
Sponsors
Janssen Pharmaceutical K.K.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participant must have histologically or cytologically confirmed gastric (including gastroesophageal junction \[GEJ\]) or esophageal cancer (EC) that is locally advanced, unresectable, or metastatic, and not eligible for curative treatment * Participant must have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. If only 1 measurable lesion exists, it may be used for the screening biopsy if the baseline tumor assessment scans are performed greater than or equal to (\>=) 7 days after the biopsy * Participant must have Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 Gastric or GEJ Cancer Only - Must be refractory or ineligible to at least 2 prior lines of standard of care systemic therapy. Prior therapies must include fluoropyrimidine- and platinum-based chemotherapy. Participants with known human epidermal growth factor receptor (HER) 2 expression must have had HER2 targeting therapy as part of the prior therapy Esophageal Cancer Only \- Must be refractory or intolerant to at least 1 prior line of systemic therapy. Prior therapies must include fluoropyrimidine-, and platinum-based chemotherapy (including chemoradiation therapy given as stage intravenous \[IV\] setting)
Exclusion criteria
* Participant has an uncontrolled illness, including but not limited to the following: diabetes; ongoing or active bacterial infection (includes infection requiring treatment with antimicrobial therapy \[participants will be required to complete antibiotics 1 week before enrollment\]), symptomatic viral infection, or any other clinically significant infection; active bleeding diathesis and psychiatric illness/social situation that would limit compliance with study requirements * Participant has received prior epidermal growth factor receptor (EGFR) or tyrosine-protein kinase mesenchymal-epithelial transition (cMet)-directed therapies * Participant has had prior chemotherapy, targeted cancer therapy, immunotherapy, or treatment with an investigational anticancer agent within 2 weeks or 4 half-lives whichever is longer or had radiation therapy within 4 weeks before the first administration of study treatment. For agents with long half-lives, the maximum required time since last dose is 28 days. Toxicities from previous anticancer therapies should have resolved to baseline levels or to Grade 1 or less, (except for alopecia or post-radiation skin changes \[any grade\], Grade less than or equal to \[\<=\] 2 peripheral neuropathy, and Grade \<=2 hypothyroidism stable on hormone replacement) * Participant has untreated brain metastases (a participant with definitively, locally treated metastases who is clinically stable, asymptomatic, and off corticosteroid treatment for at least 2 weeks prior to the first administration of study treatment is eligible), history of leptomeningeal disease or spinal cord compression that has not been treated definitively with surgery or radiation. If brain metastases are diagnosed on screening imaging, the participant may be rescreened for eligibility after definitive treatment * Participant has a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, or has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening. Esophageal cancer participants with history of completely resolved radiation pneumonitis (defined as radiographically stable for 3 months prior to enrollment without need of any treatment) may be enrolled
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 | From start of the treatment (Day 1) up to 30 days after the last dose of study drug (up to 9 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 target and non-target lesions and normalization of tumor markers. Pathological lymph nodes must have short axis measures less than (\<)10 millimeter (mm). PR was defined as at least a 30 percent (%) decrease in the sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of target lesions, taking as reference baseline sum of diameters. Non-target lesions must be non-progressive disease (PD). For non-target lesions, PD: unequivocal progression of existing non-target lesions. The appearance of one or more new lesions was also considered progression. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 9 months) | DOR was defined as time between date of first documented response (CR/PR) and date of first documented progression or death, whichever occurred first. CR was defined as disappearance of target and non-target lesions and normalization of tumor markers. Pathological lymph nodes short axis measures \<10 mm. PR was defined as \>=30% decrease in sum of measures (tumor lesions-longest diameter and nodes-short axis) of target lesions, taking as reference baseline sum of diameters. Non-target lesions must be non-PD. For non-target lesions, PD: unequivocal progression of existing non-target lesions. The appearance of one or more new lesions was also considered progression. There was no participant who had event (CR/PR) in Phase 2a EC higher dose cohort, hence data could not be collected and analyzed for this cohort. |
| Time to Response (TTR) as Per RECIST Version 1.1 | From first dose of study treatment until first documentation of CR or PR (up to 9 months) | TTR was defined as time from date of first amivantamab administration to date of achieving objective response (CR/PR) as assessed by investigator per RECIST v1.1 among participants who achieved objective response. Per RECIST v1.1, CR: disappearance of target and non-target lesions and normalization of tumor markers. Pathological lymph nodes must have short axis measures \<10 mm. PR: \>=30% decrease in sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of target lesions, taking as reference baseline sum of diameters. Non-target lesions must be non-PD. For non-target lesions, PD: unequivocal progression of existing non-target lesions. The appearance of one or more new lesions was also considered progression. There was no participant who had event (CR/PR) in Phase 2a EC higher dose cohort, hence data could not be collected and analyzed for this cohort. |
| Progression Free Survival (PFS) as Per RECIST Version 1.1 | From day of first dose (Day 1) until PD or death (up to 9 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 in the absence of progression), whichever comes first, based on investigator assessment using RECIST Version 1.1. |
| 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 or start of new anticancer therapy, whichever occurred first (up to 9 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 v5.0. 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 are reported in this outcome measure. |
| Maximum Observed Serum Concentration (Cmax) for Amivantamab | Pre-dose, 0, 24, 26, 48, 72, 96 and 168 hours post-dose on Day 1 of Cycle 1; pre-dose, 0, 2, 24, 48, 72, 168 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. Data for this outcome measure was planned to be collected and analyzed for each cancer type (GC and EC) and overall participants (GC and EC combined cohorts: Amivantamab \[1050/1400 mg\]). As planned, data for Cmax was not collected and analyzed for Phase 2a EC higher dose cohort. |
| Time to Reach Maximum Observed Serum Concentration (Tmax) for Amivantamab | Pre-dose, 0, 24, 26, 48, 72, 96 and 168 hours post-dose on Day 1 of Cycle 1; pre-dose, 0, 2, 24, 48, 72, 168 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. Data for this outcome measure was planned to be collected and analyzed for each cancer type (GC and EC) and overall participants (GC and EC combined cohorts: Amivantamab \[1050/1400 mg\]). As planned, data for Tmax was not collected and analyzed for Phase 2a EC higher dose cohort. |
| Area Under the Curve From Time (0) to Time (168h) (AUC [0-168h]) for Amivantamab | Pre-dose, 0, 24, 26, 48, 72, 96 and 168 hours post-dose on Day 1 of Cycle 1 (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. Data for this outcome measure was planned to be collected and analyzed for each cancer type (GC and EC) and overall participants (GC and EC combined cohorts: Amivantamab \[1050/1400 mg\]). As planned, data for AUC (0-168h) was not collected and analyzed for Phase 2a EC higher dose cohort. |
| Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Amivantamab | Pre-dose, 0, 2, 24, 48, 72, 168 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 was 336 hours was reported. The concentrations of amivantamab were measured using a validated, specific, and sensitive ELISA method. Data for this outcome measure was planned to be collected and analyzed for each cancer type (GC and EC) and overall participants (GC and EC combined cohorts: Amivantamab \[1050/1400 mg\]). As planned, data for AUCtau was not collected and analyzed for Phase 2a EC higher dose cohort. |
| Disease Control Rate (DCR) Per RECIST Version 1.1 | From start of the treatment (Day 1) up to 30 days after the last dose of study drug (up to 9 months) | DCR was defined as the percentage of participants achieving CR or PR or stable disease (SD) for at least 6 weeks as defined by RECIST version 1.1. As per RECIST version 1.1 CR was defined as disappearance of target and non-target lesions and normalization of tumor markers. Pathological lymph nodes must have short axis measures \<10 mm. PR was defined as \>=30% decrease in sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of target lesions, taking as reference baseline sum of diameters. Non-target lesions must be non-PD. For non-target lesions, PD: unequivocal progression of existing non-target lesions. The appearance of one or more new lesions was also considered progression. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, and no appearance of new lesion(s). |
| Phase 2a Esophageal Cancer Higher Dose Cohort: Serum Trough Concentrations (Ctrough) of Amivantamab | Pre-dose at 0 hour: Day 15 of Cycle 1; Days 1 and 15 of Cycles 2 and 3; Day 1 of Cycles 6 and 8 (each cycle was of 28 days) | Ctrough of amivantamab in phase 2a EC higher dose cohort was reported. Ctrough was defined as pre-dose serum drug concentration. The concentrations of amivantamab were measured using a validated, specific, and sensitive ELISA method. |
| Phase 2a Gastric Cancer Cohort: Terminal Elimination Half-Life (t1/2) for Amivantamab | Pre-dose, 0, 2, 24, 48, 72, 168 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. |
| Phase 2a Esophageal Cancer and Overall Combined Cohorts: Terminal Elimination Half-Life (t1/2) for Amivantamab | Pre-dose, 0, 2, 24, 48, 72, 168 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. Data for this outcome measure was planned to be collected and analyzed for EC cohort and overall participants (GC and EC combined cohorts: Amivantamab \[1050/1400 mg\]). As planned, data for t1/2 was not collected and analyzed for Phase 2a EC higher dose cohort. |
| Apparent Clearance at Steady State (CLss) of Amivantamab | Pre-dose, 0, 2, 24, 48, 72, 168 and 336 hours post-dose on Day 1 of Cycle 2 (each cycle was of 28 days) | Clearance was a measure of the rate at which a drug was metabolized or eliminated by normal biological processes. The concentrations of amivantamab were measured using a validated, specific, and sensitive ELISA method. Data for this outcome measure was planned to be collected and analyzed for each cancer type (GC and EC) and overall participants (GC and EC combined cohorts: Amivantamab \[1050/1400 mg\]). As planned, data for CLss was not collected and analyzed for Phase 2a EC higher dose cohort. |
| Apparent Volume of Distribution at Steady State (Vss) of Amivantamab | Pre-dose, 0, 2, 24, 48, 72, 168 and 336 hours post-dose on Day 1 of Cycle 2 (each cycle was of 28 days) | Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug. The concentrations of amivantamab were measured using a validated, specific, and sensitive ELISA method. Data for this outcome measure was planned to be collected and analyzed for each cancer type (GC and EC) and overall participants (GC and EC combined cohorts: Amivantamab \[1050/1400 mg\]). As planned, data for Vss was not collected and analyzed for Phase 2a EC higher dose cohort. |
| Accumulation Ratio (AR) of AUCtau for Amivantamab | Pre-dose, 0, 24, 26, 48, 72, 96 and 168 hours post-dose on Day 1 of Cycle 1; pre-dose, 0, 2, 24, 48, 72, 168 and 336 hours post-dose on Day 1 of Cycle 2 (each cycle was of 28 days) | Accumulation ratio for AUC was calculated as AUC (0-336h) for Cycle 2 Day 1 divided by AUC (0-168h) for Cycle 1 Day 1. The concentrations of amivantamab were measured using a validated, specific, and sensitive ELISA method. Data for this outcome measure was planned to be collected and analyzed for each cancer type (GC and EC) and overall participants (GC and EC combined cohorts: Amivantamab \[1050/1400 mg\]). As planned, data for AR of AUCtau was not collected and analyzed for Phase 2a EC higher dose cohort. |
| 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 9 months) | Number of participants with anti-amivantamab antibodies were reported. Serum samples were assessed for anti-drug antibodies. |
| Phase 2a Gastric Cancer and Esophageal Cancer Cohorts: Serum Trough Concentrations (Ctrough) of Amivantamab | Pre-dose at 0 hour: Days 8 and 15 of Cycle 1; Days 1 and 15 of Cycles 2, 3 and 4; Day 1 of Cycles 6 and 8 (each cycle was of 28 days) | Ctrough of amivantamab in GC and EC cohorts 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. Data for this outcome measure was planned to be collected and analyzed for each cancer type (GC and EC) and overall participants (GC and EC combined cohorts: Amivantamab \[1050/1400 mg\]). |
Countries
Japan
Participant flow
Pre-assignment details
The study was planned to be conducted in 2 cohorts: Phase 2a cohorts (including Phase 2a extension cohort) and Phase 2b expansion cohort in participants with previously treated advanced or metastatic gastric or esophageal cancer. However, due to study termination, no participants were enrolled in Phase 2a extension cohorts and Phase 2b cohorts. Hence the results were only presented for Phase 2a cohorts.
Participants by arm
| Arm | Count |
|---|---|
| Phase 2a Gastric Cancer Cohort: Amivantamab (1050/1400 mg) Participants with previously treated advanced or metastatic gastric/gastroesophageal junction cancer (GC) exhibiting varying degrees of epidermal growth factor receptor (EGFR), tyrosine-protein kinase mesenchymal-epithelial transition (MET), or both as determined by immunohistochemistry (IHC) 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 disease progression, unacceptable toxicity, withdrawal of consent, initiation of subsequent anticancer therapy, lost to follow-up or death whichever comes first. Participants were followed up for safety up to 30 days after the last dose. | 29 |
| Phase 2a Esophageal Cancer Cohort: Amivantamab (1050/1400 mg) Participants with previously treated advanced or metastatic esophageal cancer (EC) exhibiting varying degrees of EGFR, MET, or both as determined by IHC received amivantamab 1050 mg for body weight \<80 kg or 1400 mg for body weight \>=80 kg as an IV infusion in each 28-day cycles. During Cycle 1, amivantamab was administered once weekly on Days 1, 8, 15 and 22 with the first dose split over Day 1 (350 mg) and Day 2 (700 mg for body weight \<80 kg or 1050 mg for body weight \>=80 kg). From Cycle 2 onwards, amivantamab was administered on Days 1 and 15 until disease progression, unacceptable toxicity, withdrawal of consent, initiation of subsequent anticancer therapy, lost to follow-up or death whichever comes first. Participants were followed up for safety up to 30 days after the last dose. | 30 |
| Phase 2a Esophageal Cancer Higher Dose Cohort: Amivantamab (1750/2100 mg) Participants with previously treated advanced or metastatic EC exhibiting varying degrees of EGFR, MET, or both as determined by IHC received amivantamab 1750 mg for body weight \<80 kg or 2100 mg for body weight \>=80 kg as an IV infusion in each 28-day cycles. During Cycle 1, amivantamab was administered once weekly on Days 1, 8, 15 and 22 with the first dose split over Day 1 (350 mg) and Day 2 (1400 mg for body weight \<80 kg or 1750 mg for body weight \>=80 kg). From Cycle 2 onwards, amivantamab was administered on Days 1 and 15 until disease progression, unacceptable toxicity, withdrawal of consent, initiation of subsequent anticancer therapy, lost to follow-up or death whichever comes first. Participants were followed up for safety up to 30 days after the last dose. | 3 |
| Total | 62 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Physician Decision | 1 | 3 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 3 | 0 |
Baseline characteristics
| Characteristic | Phase 2a Gastric Cancer Cohort: Amivantamab (1050/1400 mg) | Phase 2a Esophageal Cancer Cohort: Amivantamab (1050/1400 mg) | Phase 2a Esophageal Cancer Higher Dose Cohort: Amivantamab (1750/2100 mg) | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 16 Participants | 12 Participants | 1 Participants | 29 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants | 18 Participants | 2 Participants | 33 Participants |
| Age, Continuous | 64 years STANDARD_DEVIATION 11.97 | 62.7 years STANDARD_DEVIATION 10.35 | 60 years STANDARD_DEVIATION 9 | 63.2 years STANDARD_DEVIATION 10.97 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 29 Participants | 30 Participants | 3 Participants | 62 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 29 Participants | 30 Participants | 3 Participants | 62 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment JAPAN | 29 Participants | 30 Participants | 3 Participants | 62 Participants |
| Sex: Female, Male Female | 5 Participants | 6 Participants | 0 Participants | 11 Participants |
| Sex: Female, Male Male | 24 Participants | 24 Participants | 3 Participants | 51 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 5 / 29 | 2 / 30 | 0 / 3 |
| other Total, other adverse events | 28 / 29 | 30 / 30 | 3 / 3 |
| serious Total, serious adverse events | 9 / 29 | 7 / 30 | 0 / 3 |
Outcome results
Primary
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1
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 target and non-target lesions and normalization of tumor markers. Pathological lymph nodes must have short axis measures less than (\<)10 millimeter (mm). PR was defined as at least a 30 percent (%) decrease in the sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of target lesions, taking as reference baseline sum of diameters. Non-target lesions must be non-progressive disease (PD). For non-target lesions, PD: unequivocal progression of existing non-target lesions. The appearance of one or more new lesions was also considered progression.
Time frame: From start of the treatment (Day 1) up to 30 days after the last dose of study drug (up to 9 months)
Population: Response evaluable analysis set included all participants who received at least 1 dose of study treatment, met all eligibility criteria for the study and had a baseline and at least 1 post-baseline efficacy disease assessments, or had disease progression/death due to disease progression prior to the first post-baseline disease assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 2a Gastric Cancer Cohort: Amivantamab (1050/1400 mg) | Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 | 4.3 Percentage of Participants |
| Phase 2a Esophageal Cancer Cohort: Amivantamab (1050/1400 mg) | Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 | 10.7 Percentage of Participants |
| Phase 2a Esophageal Cancer Higher Dose Cohort: Amivantamab (1750/2100 mg) | Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 | 0 Percentage of Participants |
Secondary
Accumulation Ratio (AR) of AUCtau for Amivantamab
Accumulation ratio for AUC was calculated as AUC (0-336h) for Cycle 2 Day 1 divided by AUC (0-168h) for Cycle 1 Day 1. The concentrations of amivantamab were measured using a validated, specific, and sensitive ELISA method. Data for this outcome measure was planned to be collected and analyzed for each cancer type (GC and EC) and overall participants (GC and EC combined cohorts: Amivantamab \[1050/1400 mg\]). As planned, data for AR of AUCtau was not collected and analyzed for Phase 2a EC higher dose cohort.
Time frame: Pre-dose, 0, 24, 26, 48, 72, 96 and 168 hours post-dose on Day 1 of Cycle 1; pre-dose, 0, 2, 24, 48, 72, 168 and 336 hours post-dose on Day 1 of Cycle 2 (each cycle was of 28 days)
Population: The PK analysis set included all participants who received at least 1 dose of study treatment and had at least 1 evaluable post-baseline measurement. Here 'N' (overall number of participants analyzed) refers to the participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase 2a Gastric Cancer Cohort: Amivantamab (1050/1400 mg) | Accumulation Ratio (AR) of AUCtau for Amivantamab | 4.32 Ratio | Standard Deviation 0.51 |
| Phase 2a Esophageal Cancer Cohort: Amivantamab (1050/1400 mg) | Accumulation Ratio (AR) of AUCtau for Amivantamab | 5.12 Ratio | Standard Deviation 0.72 |
| Overall: Phase 2a GC and EC Combined Cohorts: Amivantamab (1050/1400 mg) | Accumulation Ratio (AR) of AUCtau for Amivantamab | 4.85 Ratio | Standard Deviation 0.74 |
Secondary
Apparent Clearance at Steady State (CLss) of Amivantamab
Clearance was a measure of the rate at which a drug was metabolized or eliminated by normal biological processes. The concentrations of amivantamab were measured using a validated, specific, and sensitive ELISA method. Data for this outcome measure was planned to be collected and analyzed for each cancer type (GC and EC) and overall participants (GC and EC combined cohorts: Amivantamab \[1050/1400 mg\]). As planned, data for CLss was not collected and analyzed for Phase 2a EC higher dose cohort.
Time frame: Pre-dose, 0, 2, 24, 48, 72, 168 and 336 hours post-dose on Day 1 of Cycle 2 (each cycle was of 28 days)
Population: The PK analysis set included all participants who received at least 1 dose of study treatment and had at least 1 evaluable post-baseline measurement. Here 'N' (overall number of participants analyzed) refers to the participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase 2a Gastric Cancer Cohort: Amivantamab (1050/1400 mg) | Apparent Clearance at Steady State (CLss) of Amivantamab | 0.00775 Liters/hour (L/h) | Standard Deviation 0.00122 |
| Phase 2a Esophageal Cancer Cohort: Amivantamab (1050/1400 mg) | Apparent Clearance at Steady State (CLss) of Amivantamab | 0.00695 Liters/hour (L/h) | Standard Deviation 0.002 |
| Overall: Phase 2a GC and EC Combined Cohorts: Amivantamab (1050/1400 mg) | Apparent Clearance at Steady State (CLss) of Amivantamab | 0.00722 Liters/hour (L/h) | Standard Deviation 0.00176 |
Secondary
Apparent Volume of Distribution at Steady State (Vss) of Amivantamab
Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug. The concentrations of amivantamab were measured using a validated, specific, and sensitive ELISA method. Data for this outcome measure was planned to be collected and analyzed for each cancer type (GC and EC) and overall participants (GC and EC combined cohorts: Amivantamab \[1050/1400 mg\]). As planned, data for Vss was not collected and analyzed for Phase 2a EC higher dose cohort.
Time frame: Pre-dose, 0, 2, 24, 48, 72, 168 and 336 hours post-dose on Day 1 of Cycle 2 (each cycle was of 28 days)
Population: The PK analysis set included all participants who received at least 1 dose of study treatment and had at least 1 evaluable post-baseline measurement. Here 'N' (overall number of participants analyzed) refers to the participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase 2a Gastric Cancer Cohort: Amivantamab (1050/1400 mg) | Apparent Volume of Distribution at Steady State (Vss) of Amivantamab | 3.59 Liters | — |
| Phase 2a Esophageal Cancer Cohort: Amivantamab (1050/1400 mg) | Apparent Volume of Distribution at Steady State (Vss) of Amivantamab | 2.61 Liters | Standard Deviation 1.04 |
| Overall: Phase 2a GC and EC Combined Cohorts: Amivantamab (1050/1400 mg) | Apparent Volume of Distribution at Steady State (Vss) of Amivantamab | 2.75 Liters | Standard Deviation 1.02 |
Secondary
Area Under the Curve From Time (0) to Time (168h) (AUC [0-168h]) for 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. Data for this outcome measure was planned to be collected and analyzed for each cancer type (GC and EC) and overall participants (GC and EC combined cohorts: Amivantamab \[1050/1400 mg\]). As planned, data for AUC (0-168h) was not collected and analyzed for Phase 2a EC higher dose cohort.
Time frame: Pre-dose, 0, 24, 26, 48, 72, 96 and 168 hours post-dose on Day 1 of Cycle 1 (each cycle was of 28 days)
Population: The PK analysis set included all participants who received at least 1 dose of study treatment and had at least 1 evaluable post-baseline measurement. Here 'N' (overall number of participants analyzed) refers to the participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase 2a Gastric Cancer Cohort: Amivantamab (1050/1400 mg) | Area Under the Curve From Time (0) to Time (168h) (AUC [0-168h]) for Amivantamab | 30990 micrograms*hours/milliliter (mcg*hr/mL) | Standard Deviation 8346 |
| Phase 2a Esophageal Cancer Cohort: Amivantamab (1050/1400 mg) | Area Under the Curve From Time (0) to Time (168h) (AUC [0-168h]) for Amivantamab | 31548 micrograms*hours/milliliter (mcg*hr/mL) | Standard Deviation 7854 |
| Overall: Phase 2a GC and EC Combined Cohorts: Amivantamab (1050/1400 mg) | Area Under the Curve From Time (0) to Time (168h) (AUC [0-168h]) for Amivantamab | 31269 micrograms*hours/milliliter (mcg*hr/mL) | Standard Deviation 7930 |
Secondary
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Amivantamab
Area under the serum concentration curve from time 0 to end of dosing interval (AUCtau), where dosing interval was 336 hours was reported. The concentrations of amivantamab were measured using a validated, specific, and sensitive ELISA method. Data for this outcome measure was planned to be collected and analyzed for each cancer type (GC and EC) and overall participants (GC and EC combined cohorts: Amivantamab \[1050/1400 mg\]). As planned, data for AUCtau was not collected and analyzed for Phase 2a EC higher dose cohort.
Time frame: Pre-dose, 0, 2, 24, 48, 72, 168 and 336 hours post-dose on Day 1 of Cycle 2 (each cycle was of 28 days)
Population: The PK analysis set included all participants who received at least 1 dose of study treatment and had at least 1 evaluable post-baseline measurement. Here 'N' (overall number of participants analyzed) refers to the participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase 2a Gastric Cancer Cohort: Amivantamab (1050/1400 mg) | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Amivantamab | 137806 micrograms*hours/milliliter (mcg*hr/mL) | Standard Deviation 19006 |
| Phase 2a Esophageal Cancer Cohort: Amivantamab (1050/1400 mg) | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Amivantamab | 162171 micrograms*hours/milliliter (mcg*hr/mL) | Standard Deviation 45328 |
| Overall: Phase 2a GC and EC Combined Cohorts: Amivantamab (1050/1400 mg) | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Amivantamab | 154049 micrograms*hours/milliliter (mcg*hr/mL) | Standard Deviation 39369 |
Secondary
Disease Control Rate (DCR) Per RECIST Version 1.1
DCR was defined as the percentage of participants achieving CR or PR or stable disease (SD) for at least 6 weeks as defined by RECIST version 1.1. As per RECIST version 1.1 CR was defined as disappearance of target and non-target lesions and normalization of tumor markers. Pathological lymph nodes must have short axis measures \<10 mm. PR was defined as \>=30% decrease in sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of target lesions, taking as reference baseline sum of diameters. Non-target lesions must be non-PD. For non-target lesions, PD: unequivocal progression of existing non-target lesions. The appearance of one or more new lesions was also considered progression. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, and no appearance of new lesion(s).
Time frame: From start of the treatment (Day 1) up to 30 days after the last dose of study drug (up to 9 months)
Population: Response evaluable analysis set included all participants who received at least 1 dose of study treatment, met all eligibility criteria for the study and had a baseline and at least 1 post-baseline efficacy disease assessments, or had disease progression/death due to disease progression prior to the first post-baseline disease assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Phase 2a Gastric Cancer Cohort: Amivantamab (1050/1400 mg) | Disease Control Rate (DCR) Per RECIST Version 1.1 | 26.1 Percentage of Participants |
| Phase 2a Esophageal Cancer Cohort: Amivantamab (1050/1400 mg) | Disease Control Rate (DCR) Per RECIST Version 1.1 | 67.9 Percentage of Participants |
| Phase 2a Esophageal Cancer Higher Dose Cohort: Amivantamab (1750/2100 mg) | Disease Control Rate (DCR) Per RECIST Version 1.1 | 100 Percentage of Participants |
Secondary
Duration of Response (DOR) as Per RECIST Version 1.1
DOR was defined as time between date of first documented response (CR/PR) and date of first documented progression or death, whichever occurred first. CR was defined as disappearance of target and non-target lesions and normalization of tumor markers. Pathological lymph nodes short axis measures \<10 mm. PR was defined as \>=30% decrease in sum of measures (tumor lesions-longest diameter and nodes-short axis) of target lesions, taking as reference baseline sum of diameters. Non-target lesions must be non-PD. For non-target lesions, PD: unequivocal progression of existing non-target lesions. The appearance of one or more new lesions was also considered progression. There was no participant who had event (CR/PR) in Phase 2a EC higher dose cohort, hence data could not be collected and analyzed for this cohort.
Time frame: From the date of first documented response up to date of first documented PD or death (up to 9 months)
Population: Response evaluable analysis set included all participants who received at least 1 dose of study treatment, met all eligibility criteria for study and had a baseline and at least 1 post-baseline efficacy disease assessments, or had disease progression/death due to disease progression prior to first post-baseline disease assessment. Here 'N' (overall number of participants analyzed) = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 2a Gastric Cancer Cohort: Amivantamab (1050/1400 mg) | Duration of Response (DOR) as Per RECIST Version 1.1 | NA Months |
| Phase 2a Esophageal Cancer Cohort: Amivantamab (1050/1400 mg) | Duration of Response (DOR) as Per RECIST Version 1.1 | 2.86 Months |
Secondary
Maximum Observed Serum Concentration (Cmax) for 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. Data for this outcome measure was planned to be collected and analyzed for each cancer type (GC and EC) and overall participants (GC and EC combined cohorts: Amivantamab \[1050/1400 mg\]). As planned, data for Cmax was not collected and analyzed for Phase 2a EC higher dose cohort.
Time frame: Pre-dose, 0, 24, 26, 48, 72, 96 and 168 hours post-dose on Day 1 of Cycle 1; pre-dose, 0, 2, 24, 48, 72, 168 and 336 hours post-dose on Day 1 of Cycle 2 (each cycle was of 28 days)
Population: The pharmacokinetics (PK) analysis set included all participants who received at least 1 dose of study treatment and had at least 1 evaluable post-baseline measurement. Here 'N' (overall number of participants analyzed) = participants evaluable for this outcome measure and 'n' (number analyzed) = refers to participants evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 2a Gastric Cancer Cohort: Amivantamab (1050/1400 mg) | Maximum Observed Serum Concentration (Cmax) for Amivantamab | Cycle 1 Day 1 | 356 Micrograms per milliliter (mcg/mL) | Standard Deviation 91.6 |
| Phase 2a Gastric Cancer Cohort: Amivantamab (1050/1400 mg) | Maximum Observed Serum Concentration (Cmax) for Amivantamab | Cycle 2 Day 1 | 820 Micrograms per milliliter (mcg/mL) | Standard Deviation 221 |
| Phase 2a Esophageal Cancer Cohort: Amivantamab (1050/1400 mg) | Maximum Observed Serum Concentration (Cmax) for Amivantamab | Cycle 1 Day 1 | 370 Micrograms per milliliter (mcg/mL) | Standard Deviation 78.2 |
| Phase 2a Esophageal Cancer Cohort: Amivantamab (1050/1400 mg) | Maximum Observed Serum Concentration (Cmax) for Amivantamab | Cycle 2 Day 1 | 866 Micrograms per milliliter (mcg/mL) | Standard Deviation 196 |
| Overall: Phase 2a GC and EC Combined Cohorts: Amivantamab (1050/1400 mg) | Maximum Observed Serum Concentration (Cmax) for Amivantamab | Cycle 1 Day 1 | 363 Micrograms per milliliter (mcg/mL) | Standard Deviation 84 |
| Overall: Phase 2a GC and EC Combined Cohorts: Amivantamab (1050/1400 mg) | Maximum Observed Serum Concentration (Cmax) for Amivantamab | Cycle 2 Day 1 | 845 Micrograms per milliliter (mcg/mL) | Standard Deviation 202 |
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 9 months)
Population: The immunogenicity analysis set included all participants who received at least 1 dose of study treatment and had at least 1 evaluable post-baseline measurement.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 2a Gastric Cancer Cohort: Amivantamab (1050/1400 mg) | Number of Participants With Anti-Amivantamab Antibodies | 0 Participants |
| Phase 2a Esophageal Cancer Cohort: Amivantamab (1050/1400 mg) | Number of Participants With Anti-Amivantamab Antibodies | 0 Participants |
| Phase 2a Esophageal Cancer Higher Dose Cohort: Amivantamab (1750/2100 mg) | Number of Participants With Anti-Amivantamab Antibodies | 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 v5.0. 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 are reported in this outcome measure.
Time frame: From start of the treatment (Day 1) up to 30 days after last dose or start of new anticancer therapy, whichever occurred first (up to 9 months)
Population: The safety analysis set included all participants who took at least 1 dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 2a Gastric Cancer Cohort: Amivantamab (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 |
| Phase 2a Gastric Cancer Cohort: Amivantamab (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 | 8 Participants |
| Phase 2a Gastric Cancer Cohort: Amivantamab (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 | 4 Participants |
| Phase 2a Gastric Cancer Cohort: Amivantamab (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 | 14 Participants |
| Phase 2a Gastric Cancer Cohort: Amivantamab (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 | 3 Participants |
| Phase 2a Esophageal Cancer Cohort: Amivantamab (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 | 9 Participants |
| Phase 2a Esophageal Cancer Cohort: Amivantamab (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 | 3 Participants |
| Phase 2a Esophageal Cancer Cohort: Amivantamab (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 | 17 Participants |
| Phase 2a Esophageal Cancer Cohort: Amivantamab (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 |
| Phase 2a Esophageal Cancer Cohort: Amivantamab (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 |
| Phase 2a Esophageal Cancer Higher Dose Cohort: Amivantamab (1750/2100 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 | 0 Participants |
| Phase 2a Esophageal Cancer Higher Dose Cohort: Amivantamab (1750/2100 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 |
| Phase 2a Esophageal Cancer Higher Dose Cohort: Amivantamab (1750/2100 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 | 1 Participants |
| Phase 2a Esophageal Cancer Higher Dose Cohort: Amivantamab (1750/2100 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 | 1 Participants |
| Phase 2a Esophageal Cancer Higher Dose Cohort: Amivantamab (1750/2100 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 | 1 Participants |
Secondary
Phase 2a Esophageal Cancer and Overall Combined Cohorts: Terminal Elimination Half-Life (t1/2) for 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. Data for this outcome measure was planned to be collected and analyzed for EC cohort and overall participants (GC and EC combined cohorts: Amivantamab \[1050/1400 mg\]). As planned, data for t1/2 was not collected and analyzed for Phase 2a EC higher dose cohort.
Time frame: Pre-dose, 0, 2, 24, 48, 72, 168 and 336 hours post-dose on Day 1 of Cycle 2 (each cycle was of 28 days)
Population: The PK analysis set included all participants who received at least 1 dose of study treatment and had at least 1 evaluable post-baseline measurement. Here 'N' (overall number of participants analyzed) refers to the participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase 2a Gastric Cancer Cohort: Amivantamab (1050/1400 mg) | Phase 2a Esophageal Cancer and Overall Combined Cohorts: Terminal Elimination Half-Life (t1/2) for Amivantamab | 254.7 Hours | Standard Deviation 43 |
| Phase 2a Esophageal Cancer Higher Dose Cohort: Amivantamab (1750/2100 mg) | Phase 2a Esophageal Cancer and Overall Combined Cohorts: Terminal Elimination Half-Life (t1/2) for Amivantamab | 252.6 Hours | Standard Deviation 38.7 |
Secondary
Phase 2a Esophageal Cancer Higher Dose Cohort: Serum Trough Concentrations (Ctrough) of Amivantamab
Ctrough of amivantamab in phase 2a EC higher dose cohort was 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: Day 15 of Cycle 1; Days 1 and 15 of Cycles 2 and 3; Day 1 of Cycles 6 and 8 (each cycle was of 28 days)
Population: The PK analysis set included all participants who received at least 1 dose of study treatment and had at least 1 evaluable post-baseline measurement. Here 'N' (overall number of participants analyzed) = the participants evaluable for this outcome measure and 'n' (number analyzed) = participants evaluable at specified time points. As planned participant wise data was collected and analyzed when n was less than (\<) 3.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Phase 2a Gastric Cancer Cohort: Amivantamab (1050/1400 mg) | Phase 2a Esophageal Cancer Higher Dose Cohort: Serum Trough Concentrations (Ctrough) of Amivantamab | Pre-dose Cycle 1 Day 15: Participant 1 | 333 Micrograms per milliliter (mcg/mL) |
| Phase 2a Gastric Cancer Cohort: Amivantamab (1050/1400 mg) | Phase 2a Esophageal Cancer Higher Dose Cohort: Serum Trough Concentrations (Ctrough) of Amivantamab | Pre-dose Cycle 1 Day 15: Participant 2 | 337 Micrograms per milliliter (mcg/mL) |
| Phase 2a Gastric Cancer Cohort: Amivantamab (1050/1400 mg) | Phase 2a Esophageal Cancer Higher Dose Cohort: Serum Trough Concentrations (Ctrough) of Amivantamab | Pre-dose Cycle 2 Day 1: Participant 1 | 657 Micrograms per milliliter (mcg/mL) |
| Phase 2a Gastric Cancer Cohort: Amivantamab (1050/1400 mg) | Phase 2a Esophageal Cancer Higher Dose Cohort: Serum Trough Concentrations (Ctrough) of Amivantamab | Pre-dose Cycle 2 Day 1: Participant 2 | 779 Micrograms per milliliter (mcg/mL) |
| Phase 2a Gastric Cancer Cohort: Amivantamab (1050/1400 mg) | Phase 2a Esophageal Cancer Higher Dose Cohort: Serum Trough Concentrations (Ctrough) of Amivantamab | Pre-dose Cycle 2 Day 15: Participant 1 | 590 Micrograms per milliliter (mcg/mL) |
| Phase 2a Gastric Cancer Cohort: Amivantamab (1050/1400 mg) | Phase 2a Esophageal Cancer Higher Dose Cohort: Serum Trough Concentrations (Ctrough) of Amivantamab | Pre-dose Cycle 2 Day 15: Participant 2 | 604 Micrograms per milliliter (mcg/mL) |
| Phase 2a Gastric Cancer Cohort: Amivantamab (1050/1400 mg) | Phase 2a Esophageal Cancer Higher Dose Cohort: Serum Trough Concentrations (Ctrough) of Amivantamab | Pre-dose Cycle 3 Day 1: Participant 1 | 433 Micrograms per milliliter (mcg/mL) |
| Phase 2a Gastric Cancer Cohort: Amivantamab (1050/1400 mg) | Phase 2a Esophageal Cancer Higher Dose Cohort: Serum Trough Concentrations (Ctrough) of Amivantamab | Pre-dose Cycle 3 Day 1: Participant 2 | 600 Micrograms per milliliter (mcg/mL) |
| Phase 2a Gastric Cancer Cohort: Amivantamab (1050/1400 mg) | Phase 2a Esophageal Cancer Higher Dose Cohort: Serum Trough Concentrations (Ctrough) of Amivantamab | Pre-dose Cycle 3 Day 15: Participant 1 | 460 Micrograms per milliliter (mcg/mL) |
| Phase 2a Gastric Cancer Cohort: Amivantamab (1050/1400 mg) | Phase 2a Esophageal Cancer Higher Dose Cohort: Serum Trough Concentrations (Ctrough) of Amivantamab | Pre-dose Cycle 6 Day 1: Participant 1 | 295 Micrograms per milliliter (mcg/mL) |
| Phase 2a Gastric Cancer Cohort: Amivantamab (1050/1400 mg) | Phase 2a Esophageal Cancer Higher Dose Cohort: Serum Trough Concentrations (Ctrough) of Amivantamab | Pre-dose Cycle 8 Day 1: Participant 1 | 314 Micrograms per milliliter (mcg/mL) |
Secondary
Phase 2a Gastric Cancer and Esophageal Cancer Cohorts: Serum Trough Concentrations (Ctrough) of Amivantamab
Ctrough of amivantamab in GC and EC cohorts 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. Data for this outcome measure was planned to be collected and analyzed for each cancer type (GC and EC) and overall participants (GC and EC combined cohorts: Amivantamab \[1050/1400 mg\]).
Time frame: Pre-dose at 0 hour: Days 8 and 15 of Cycle 1; Days 1 and 15 of Cycles 2, 3 and 4; Day 1 of Cycles 6 and 8 (each cycle was of 28 days)
Population: The PK analysis set included all participants who received at least 1 dose of study treatment and had at least 1 evaluable post-baseline measurement. Here 'N' (overall number of participants analyzed) = participants evaluable for this outcome measure and 'n' (number analyzed) = refers to participants evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 2a Gastric Cancer Cohort: Amivantamab (1050/1400 mg) | Phase 2a Gastric Cancer and Esophageal Cancer Cohorts: Serum Trough Concentrations (Ctrough) of Amivantamab | Pre-dose Cycle 1 Day 15 | 214 Micrograms per milliliter (mcg/mL) | Standard Deviation 73.7 |
| Phase 2a Gastric Cancer Cohort: Amivantamab (1050/1400 mg) | Phase 2a Gastric Cancer and Esophageal Cancer Cohorts: Serum Trough Concentrations (Ctrough) of Amivantamab | Pre-dose Cycle 4 Day 15 | 139.0 Micrograms per milliliter (mcg/mL) | — |
| Phase 2a Gastric Cancer Cohort: Amivantamab (1050/1400 mg) | Phase 2a Gastric Cancer and Esophageal Cancer Cohorts: Serum Trough Concentrations (Ctrough) of Amivantamab | Pre-dose Cycle 6 Day 1 | 122.3 Micrograms per milliliter (mcg/mL) | — |
| Phase 2a Gastric Cancer Cohort: Amivantamab (1050/1400 mg) | Phase 2a Gastric Cancer and Esophageal Cancer Cohorts: Serum Trough Concentrations (Ctrough) of Amivantamab | Pre-dose Cycle 8 Day 1 | 111.4 Micrograms per milliliter (mcg/mL) | — |
| Phase 2a Gastric Cancer Cohort: Amivantamab (1050/1400 mg) | Phase 2a Gastric Cancer and Esophageal Cancer Cohorts: Serum Trough Concentrations (Ctrough) of Amivantamab | Pre-dose Cycle 2 Day 1 | 308 Micrograms per milliliter (mcg/mL) | Standard Deviation 99.5 |
| Phase 2a Gastric Cancer Cohort: Amivantamab (1050/1400 mg) | Phase 2a Gastric Cancer and Esophageal Cancer Cohorts: Serum Trough Concentrations (Ctrough) of Amivantamab | Pre-dose Cycle 2 Day 15 | 231 Micrograms per milliliter (mcg/mL) | Standard Deviation 85.6 |
| Phase 2a Gastric Cancer Cohort: Amivantamab (1050/1400 mg) | Phase 2a Gastric Cancer and Esophageal Cancer Cohorts: Serum Trough Concentrations (Ctrough) of Amivantamab | Pre-dose Cycle 3 Day 1 | 166 Micrograms per milliliter (mcg/mL) | Standard Deviation 86.6 |
| Phase 2a Gastric Cancer Cohort: Amivantamab (1050/1400 mg) | Phase 2a Gastric Cancer and Esophageal Cancer Cohorts: Serum Trough Concentrations (Ctrough) of Amivantamab | Pre-dose Cycle 1 Day 8 | 119 Micrograms per milliliter (mcg/mL) | Standard Deviation 34.9 |
| Phase 2a Gastric Cancer Cohort: Amivantamab (1050/1400 mg) | Phase 2a Gastric Cancer and Esophageal Cancer Cohorts: Serum Trough Concentrations (Ctrough) of Amivantamab | Pre-dose Cycle 3 Day 15 | 154 Micrograms per milliliter (mcg/mL) | Standard Deviation 83.3 |
| Phase 2a Gastric Cancer Cohort: Amivantamab (1050/1400 mg) | Phase 2a Gastric Cancer and Esophageal Cancer Cohorts: Serum Trough Concentrations (Ctrough) of Amivantamab | Pre-dose Cycle 4 Day 1 | 105 Micrograms per milliliter (mcg/mL) | Standard Deviation 73.2 |
| Phase 2a Esophageal Cancer Cohort: Amivantamab (1050/1400 mg) | Phase 2a Gastric Cancer and Esophageal Cancer Cohorts: Serum Trough Concentrations (Ctrough) of Amivantamab | Pre-dose Cycle 3 Day 15 | 210 Micrograms per milliliter (mcg/mL) | Standard Deviation 87.1 |
| Phase 2a Esophageal Cancer Cohort: Amivantamab (1050/1400 mg) | Phase 2a Gastric Cancer and Esophageal Cancer Cohorts: Serum Trough Concentrations (Ctrough) of Amivantamab | Pre-dose Cycle 3 Day 1 | 234 Micrograms per milliliter (mcg/mL) | Standard Deviation 58.5 |
| Phase 2a Esophageal Cancer Cohort: Amivantamab (1050/1400 mg) | Phase 2a Gastric Cancer and Esophageal Cancer Cohorts: Serum Trough Concentrations (Ctrough) of Amivantamab | Pre-dose Cycle 4 Day 15 | 203 Micrograms per milliliter (mcg/mL) | Standard Deviation 54.1 |
| Phase 2a Esophageal Cancer Cohort: Amivantamab (1050/1400 mg) | Phase 2a Gastric Cancer and Esophageal Cancer Cohorts: Serum Trough Concentrations (Ctrough) of Amivantamab | Pre-dose Cycle 1 Day 15 | 222 Micrograms per milliliter (mcg/mL) | Standard Deviation 74.6 |
| Phase 2a Esophageal Cancer Cohort: Amivantamab (1050/1400 mg) | Phase 2a Gastric Cancer and Esophageal Cancer Cohorts: Serum Trough Concentrations (Ctrough) of Amivantamab | Pre-dose Cycle 2 Day 15 | 259 Micrograms per milliliter (mcg/mL) | Standard Deviation 80.7 |
| Phase 2a Esophageal Cancer Cohort: Amivantamab (1050/1400 mg) | Phase 2a Gastric Cancer and Esophageal Cancer Cohorts: Serum Trough Concentrations (Ctrough) of Amivantamab | Pre-dose Cycle 6 Day 1 | 190 Micrograms per milliliter (mcg/mL) | Standard Deviation 35.7 |
| Phase 2a Esophageal Cancer Cohort: Amivantamab (1050/1400 mg) | Phase 2a Gastric Cancer and Esophageal Cancer Cohorts: Serum Trough Concentrations (Ctrough) of Amivantamab | Pre-dose Cycle 2 Day 1 | 342 Micrograms per milliliter (mcg/mL) | Standard Deviation 77.4 |
| Phase 2a Esophageal Cancer Cohort: Amivantamab (1050/1400 mg) | Phase 2a Gastric Cancer and Esophageal Cancer Cohorts: Serum Trough Concentrations (Ctrough) of Amivantamab | Pre-dose Cycle 4 Day 1 | 236 Micrograms per milliliter (mcg/mL) | Standard Deviation 82.8 |
| Phase 2a Esophageal Cancer Cohort: Amivantamab (1050/1400 mg) | Phase 2a Gastric Cancer and Esophageal Cancer Cohorts: Serum Trough Concentrations (Ctrough) of Amivantamab | Pre-dose Cycle 8 Day 1 | 100.0 Micrograms per milliliter (mcg/mL) | — |
| Phase 2a Esophageal Cancer Cohort: Amivantamab (1050/1400 mg) | Phase 2a Gastric Cancer and Esophageal Cancer Cohorts: Serum Trough Concentrations (Ctrough) of Amivantamab | Pre-dose Cycle 1 Day 8 | 136 Micrograms per milliliter (mcg/mL) | Standard Deviation 45.1 |
| Phase 2a Esophageal Cancer Higher Dose Cohort: Amivantamab (1750/2100 mg) | Phase 2a Gastric Cancer and Esophageal Cancer Cohorts: Serum Trough Concentrations (Ctrough) of Amivantamab | Pre-dose Cycle 8 Day 1 | NA Micrograms per milliliter (mcg/mL) | — |
| Phase 2a Esophageal Cancer Higher Dose Cohort: Amivantamab (1750/2100 mg) | Phase 2a Gastric Cancer and Esophageal Cancer Cohorts: Serum Trough Concentrations (Ctrough) of Amivantamab | Pre-dose Cycle 1 Day 15 | 218 Micrograms per milliliter (mcg/mL) | Standard Deviation 73.5 |
| Phase 2a Esophageal Cancer Higher Dose Cohort: Amivantamab (1750/2100 mg) | Phase 2a Gastric Cancer and Esophageal Cancer Cohorts: Serum Trough Concentrations (Ctrough) of Amivantamab | Pre-dose Cycle 2 Day 1 | 327 Micrograms per milliliter (mcg/mL) | Standard Deviation 88.5 |
| Phase 2a Esophageal Cancer Higher Dose Cohort: Amivantamab (1750/2100 mg) | Phase 2a Gastric Cancer and Esophageal Cancer Cohorts: Serum Trough Concentrations (Ctrough) of Amivantamab | Pre-dose Cycle 2 Day 15 | 250 Micrograms per milliliter (mcg/mL) | Standard Deviation 82 |
| Phase 2a Esophageal Cancer Higher Dose Cohort: Amivantamab (1750/2100 mg) | Phase 2a Gastric Cancer and Esophageal Cancer Cohorts: Serum Trough Concentrations (Ctrough) of Amivantamab | Pre-dose Cycle 3 Day 1 | 217 Micrograms per milliliter (mcg/mL) | Standard Deviation 70.3 |
| Phase 2a Esophageal Cancer Higher Dose Cohort: Amivantamab (1750/2100 mg) | Phase 2a Gastric Cancer and Esophageal Cancer Cohorts: Serum Trough Concentrations (Ctrough) of Amivantamab | Pre-dose Cycle 3 Day 15 | 198 Micrograms per milliliter (mcg/mL) | Standard Deviation 87.1 |
| Phase 2a Esophageal Cancer Higher Dose Cohort: Amivantamab (1750/2100 mg) | Phase 2a Gastric Cancer and Esophageal Cancer Cohorts: Serum Trough Concentrations (Ctrough) of Amivantamab | Pre-dose Cycle 4 Day 1 | 210 Micrograms per milliliter (mcg/mL) | Standard Deviation 95.4 |
| Phase 2a Esophageal Cancer Higher Dose Cohort: Amivantamab (1750/2100 mg) | Phase 2a Gastric Cancer and Esophageal Cancer Cohorts: Serum Trough Concentrations (Ctrough) of Amivantamab | Pre-dose Cycle 4 Day 15 | 198 Micrograms per milliliter (mcg/mL) | Standard Deviation 54.8 |
| Phase 2a Esophageal Cancer Higher Dose Cohort: Amivantamab (1750/2100 mg) | Phase 2a Gastric Cancer and Esophageal Cancer Cohorts: Serum Trough Concentrations (Ctrough) of Amivantamab | Pre-dose Cycle 6 Day 1 | 173 Micrograms per milliliter (mcg/mL) | Standard Deviation 44.7 |
| Phase 2a Esophageal Cancer Higher Dose Cohort: Amivantamab (1750/2100 mg) | Phase 2a Gastric Cancer and Esophageal Cancer Cohorts: Serum Trough Concentrations (Ctrough) of Amivantamab | Pre-dose Cycle 1 Day 8 | 128 Micrograms per milliliter (mcg/mL) | Standard Deviation 40.5 |
Secondary
Phase 2a Gastric Cancer Cohort: Terminal Elimination Half-Life (t1/2) for 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, 24, 48, 72, 168 and 336 hours post-dose on Day 1 of Cycle 2 (each cycle was of 28 days)
Population: The PK analysis set included all participants who received at least 1 dose of study treatment and had at least 1 evaluable post-baseline measurement. Here 'N' (overall number of participants analyzed) = the participants evaluable for this outcome measure and 'n' (number analyzed) = participants evaluable at specified row. As planned participant wise data was collected and analyzed when n was \<3.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Phase 2a Gastric Cancer Cohort: Amivantamab (1050/1400 mg) | Phase 2a Gastric Cancer Cohort: Terminal Elimination Half-Life (t1/2) for Amivantamab | Participant 1 | 226.0 Hours |
| Phase 2a Gastric Cancer Cohort: Amivantamab (1050/1400 mg) | Phase 2a Gastric Cancer Cohort: Terminal Elimination Half-Life (t1/2) for Amivantamab | Participant 2 | 264.5 Hours |
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 in the absence of progression), whichever comes first, based on investigator assessment using RECIST Version 1.1.
Time frame: From day of first dose (Day 1) until PD or death (up to 9 months)
Population: All treated analysis set included all participants who took at least 1 dose of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 2a Gastric Cancer Cohort: Amivantamab (1050/1400 mg) | Progression Free Survival (PFS) as Per RECIST Version 1.1 | 1.45 Months |
| Phase 2a Esophageal Cancer Cohort: Amivantamab (1050/1400 mg) | Progression Free Survival (PFS) as Per RECIST Version 1.1 | 4.11 Months |
| Phase 2a Esophageal Cancer Higher Dose Cohort: Amivantamab (1750/2100 mg) | Progression Free Survival (PFS) as Per RECIST Version 1.1 | 2.99 Months |
Secondary
Time to Reach Maximum Observed Serum Concentration (Tmax) for 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. Data for this outcome measure was planned to be collected and analyzed for each cancer type (GC and EC) and overall participants (GC and EC combined cohorts: Amivantamab \[1050/1400 mg\]). As planned, data for Tmax was not collected and analyzed for Phase 2a EC higher dose cohort.
Time frame: Pre-dose, 0, 24, 26, 48, 72, 96 and 168 hours post-dose on Day 1 of Cycle 1; pre-dose, 0, 2, 24, 48, 72, 168 and 336 hours post-dose on Day 1 of Cycle 2 (each cycle was of 28 days)
Population: The PK analysis set included all participants who received at least 1 dose of study treatment and had at least 1 evaluable post-baseline measurement. Here 'N' (overall number of participants analyzed) = participants evaluable for this outcome measure and 'n' (number analyzed) = refers to participants evaluable at specified time points.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Phase 2a Gastric Cancer Cohort: Amivantamab (1050/1400 mg) | Time to Reach Maximum Observed Serum Concentration (Tmax) for Amivantamab | Cycle 1 Day 1 | 28.42 Hours (h) |
| Phase 2a Gastric Cancer Cohort: Amivantamab (1050/1400 mg) | Time to Reach Maximum Observed Serum Concentration (Tmax) for Amivantamab | Cycle 2 Day 1 | 4.23 Hours (h) |
| Phase 2a Esophageal Cancer Cohort: Amivantamab (1050/1400 mg) | Time to Reach Maximum Observed Serum Concentration (Tmax) for Amivantamab | Cycle 1 Day 1 | 29.65 Hours (h) |
| Phase 2a Esophageal Cancer Cohort: Amivantamab (1050/1400 mg) | Time to Reach Maximum Observed Serum Concentration (Tmax) for Amivantamab | Cycle 2 Day 1 | 2.53 Hours (h) |
| Overall: Phase 2a GC and EC Combined Cohorts: Amivantamab (1050/1400 mg) | Time to Reach Maximum Observed Serum Concentration (Tmax) for Amivantamab | Cycle 1 Day 1 | 29.23 Hours (h) |
| Overall: Phase 2a GC and EC Combined Cohorts: Amivantamab (1050/1400 mg) | Time to Reach Maximum Observed Serum Concentration (Tmax) for Amivantamab | Cycle 2 Day 1 | 3.46 Hours (h) |
Secondary
Time to Response (TTR) as Per RECIST Version 1.1
TTR was defined as time from date of first amivantamab administration to date of achieving objective response (CR/PR) as assessed by investigator per RECIST v1.1 among participants who achieved objective response. Per RECIST v1.1, CR: disappearance of target and non-target lesions and normalization of tumor markers. Pathological lymph nodes must have short axis measures \<10 mm. PR: \>=30% decrease in sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of target lesions, taking as reference baseline sum of diameters. Non-target lesions must be non-PD. For non-target lesions, PD: unequivocal progression of existing non-target lesions. The appearance of one or more new lesions was also considered progression. There was no participant who had event (CR/PR) in Phase 2a EC higher dose cohort, hence data could not be collected and analyzed for this cohort.
Time frame: From first dose of study treatment until first documentation of CR or PR (up to 9 months)
Population: Response evaluable analysis set included all participants who received at least 1 dose of study treatment, met all eligibility criteria for study and had a baseline and at least 1 post-baseline efficacy disease assessments, or had disease progression/death due to disease progression prior to first post-baseline disease assessment. Here 'N' (overall number of participants analyzed) = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 2a Gastric Cancer Cohort: Amivantamab (1050/1400 mg) | Time to Response (TTR) as Per RECIST Version 1.1 | 1.45 Months |
| Phase 2a Esophageal Cancer Cohort: Amivantamab (1050/1400 mg) | Time to Response (TTR) as Per RECIST Version 1.1 | 1.41 Months |