A Study of Amivantamab in Participants With Previously Treated Advanced or Metastatic Gastric or Esophageal Cancer

Phase 2

Terminated

• Conditions: Stomach Neoplasms; Esophageal Neoplasms
• Interventions: Drug: Amivantamab

• Registration Number: NCT04945733
• Lead Sponsor: Janssen Pharmaceutical K.K.

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-06-23
• Study First Submitted QC: 2021-06-23
• Study First Posted: 2021-06-30
• Study Start: 2021-08-30
• Primary Completion: 2023-07-03
• Study Completion: 2023-07-03
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-28
• Last Update Posted: 2024-04-01

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 62

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Amivantamab: Gastric Cancer (GC) Cohorts	Amivantamab	Participants in Phase 2a GC cohorts will receive intravenous (IV) infusion of weight-based dose of amivantamab in 28-day cycles. Participants with body weight less than (\<) 80 kilograms (kg) will receive IV infusion of amivantamab 1,050 milligrams (mg) and participants with body weight greater than or equal to (\>=) 80 kg will receive IV infusion of amivantamab 1,400 mg once weekly in Cycle 1 and then every 2 weeks in subsequent cycles (on Days 1 and 15 of each cycle), followed by additional dosing based on body weight if recommended by clinical trial management team (CTMT) (amivantamab 1750 mg for body weight \<80 kg and 2100 mg for body weight \>=80 kg as IV infusion) every 2 weeks on Days 1 and 15 of 28 day cycle. Phase 2b GC expansion cohorts will be initiated if activity is observed within Phase 2a cohorts.
Amivantamab: Esophageal Cancer (EC) Cohorts	Amivantamab	Participants in Phase 2a EC cohorts will receive IV infusion of weight-based dose of amivantamab in 28-day cycles. Participants with body weight \<80 kg will receive IV infusion of amivantamab 1,050 mg and participants with body weight \>=80 kg will receive IV infusion of amivantamab 1,400 mg once weekly in Cycle 1 and then every 2 weeks in subsequent cycles (on Days 1 and 15 of each cycle) followed by additional dosing based on body weight if recommended by CTMT (amivantamab 1750 mg for body weight \<80 kg and 2100 mg for body weight \>=80 kg as IV infusion) every 2 weeks on Days 1 and 15 of 28 day cycle. Phase 2b EC expansion cohorts will be initiated if activity is observed within Phase 2a cohorts.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	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.
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.
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).
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.
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 \[1050/1400 mg\]).
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.
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.

Trial Locations

Locations (10)

National Cancer Center Hospital; 🇯🇵 Chuo Ku, Japan

National Cancer Center Hospital East; 🇯🇵 Kashiwa, Japan

Saitama Cancer center; 🇯🇵 Kitaadachi-gun, Japan

Niigata Cancer Center Hospital; 🇯🇵 Niigata, Japan

Hokkaido University Hospital; 🇯🇵 Sapporo-shi, Japan

Tohoku University Hospital; 🇯🇵 Sendai, Japan

Osaka University Hospital; 🇯🇵 Suita-shi, Japan

Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital; 🇯🇵 Tokyo, Japan

The Cancer Institute Hospital of JFCR; 🇯🇵 Tokyo, Japan

Yokohama City University Medical Center; 🇯🇵 Yokohama, Japan