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

JRCT ID: jRCT2031210198

Registered date:15/07/2021

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Stomach Neoplasms, Esophageal Neoplasms
• Date of first enrollment: 08/09/2021
• Target sample size: 79
• Study type: Interventional

Intervention(s)

Amivantamab
Amivantamab will be administered intravenously.
Participants in Phase 2a GC/EC 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/EC expansion cohorts will be initiated if activity is observed within Phase 2a cohorts.

Outcome(s)

Primary Outcome

Objective Response Rate (ORR)
Up to 1 year and 10 months
ORR is defined as the percentage of
participants who achieve either complete response (CR) or partial response (PR), determined by investigator assessment using response evaluation criteria in solid tumors (RECIST) version 1.1.

Secondary Outcome

Disease Control Rate (DCR)
Up to 1 year and 10 months
DCR is defined as the percentage of participants achieving complete or partial response or stable disease for at least 6 weeks as defined by RECIST Version1.1.

Duration of Response (DOR)
Up to 1 year and 10 months
DOR is defined as the time from the date of first documented response (CR or PR) until the date of documented progression or death, whichever comes first.

Time to Response (TTR)
Up to 1 year and 10 months
TTR is defined as the time from the date of first amivantamab administration to the date of achieving objective response (CR or PR) by investigator assessment using RECIST Version 1.1 among participants who achieve objective response.

Progression-free Survival (PFS)
Up to 1 year and 10 months
PFS is defined as the time from first dose 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.

Phase 2b: Overall Survival (OS)
Up to 1 year and 10 months
OS is defined as the time from the date of first dose until the date of death due to any cause.

Number of Participants with Adverse Events (AEs)
Up to 1 year and 10 months
An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/ biological agent under study. Severity of AEs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event.

Maximum Serum Concentration (Cmax) of Amivantamab
Up to 1 year and 10 months
Cmax is defined as maximum concentration of amivantamab.

Time to Reach Maximum Concentration (Tmax) of Amivantamab
Up to 1 year and 10 months
Tmax is defined as time to reach maximum serum concentration of amivantamab.

Area Under the Serum Concentration-time Curve From t1 to t2 Time (AUC[t1-t2]) of Amivantamab
Up to 1 year and 10 months
AUC(t1-t2) is defined as the area under the serum concentration-time curve from time t1 to t2.

Area Under the Concentration-time Curve From Time Zero to End of Dosing Interval (AUCtau)
Up to 1 year and 10 months
AUCtau is the measure of the serum drug concentration from time zero to end of dosing interval.

Serum Concentration Immediately Prior to the Next Dose Administration (Ctrough)
Up to 1 year and 10 months
Ctrough is defined as the serum concentration of amivantamab immediately prior to the next drug administration.

Accumulation Ratio (RA) of Amivantamab
Up to 1 year and 10 months
RA is calculated as area under the plasma concentration-time curve from time zero to 24 hours (AUC [0-24]) value at steady state divided by AUC (0-24) value after first dose.

Number of Participants with Anti-Amivantamab Antibodies
Up to 1 year and 10 months
Serum samples will be collected to detect the anti-drug antibodies to amivantamab. The detection and characterization of antibodies to amivantamab will be performed using a validated immunoassay method.

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include 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)

Exclude 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

Related Information

• Primary Sponsor: Nakama Takahiro
• Secondary ID(s): NCT04945733