Clinical trial NCT04945733: A Study of Amivantamab in Participants With Previously Treated Advanced or Metastatic Gastric or Esophageal Cancer
Official title: A Phase 2, Open-label Study of Amivantamab in Subjects With Previously Treated Advanced or Metastatic Gastric or Esophageal Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Stomach Neoplasms
Esophageal Neoplasms
Lead sponsor: Janssen Pharmaceutical K.K.
Sponsor class: INDUSTRY
First posted: 2021-06-30
Enrollment: 62
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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

Primary outcomes:
measure: Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1
timeFrame: From start of the treatment (Day 1) up to 30 days after the last dose of study drug (up to 9 months)
Secondary outcomes:
measure: Disease Control Rate (DCR) Per RECIST Version 1.1
timeFrame: From start of the treatment (Day 1) up to 30 days after the last dose of study drug (up to 9 months)
measure: Duration of Response (DOR) as Per RECIST Version 1.1
timeFrame: From the date of first documented response up to date of first documented PD or death (up to 9 months)
measure: Time to Response (TTR) as Per RECIST Version 1.1
timeFrame: From first dose of study treatment until first documentation of CR or PR (up to 9 months)
measure: Progression Free Survival (PFS) as Per RECIST Version 1.1
timeFrame: From day of first dose (Day 1) until PD or death (up to 9 months)
measure: 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
timeFrame: 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)
measure: Maximum Observed Serum Concentration (Cmax) for Amivantamab
timeFrame: 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)
measure: Time to Reach Maximum Observed Serum Concentration (Tmax) for Amivantamab
timeFrame: 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)
measure: Area Under the Curve From Time (0) to Time (168h) (AUC [0-168h]) for Amivantamab
timeFrame: 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)
measure: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Amivantamab
timeFrame: 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)
measure: Phase 2a Gastric Cancer and Esophageal Cancer Cohorts: Serum Trough Concentrations (Ctrough) of Amivantamab
timeFrame: 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)
measure: Phase 2a Esophageal Cancer Higher Dose Cohort: Serum Trough Concentrations (Ctrough) of Amivantamab
timeFrame: 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)
measure: Phase 2a Gastric Cancer Cohort: Terminal Elimination Half-Life (t1/2) for Amivantamab
timeFrame: 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)
measure: Phase 2a Esophageal Cancer and Overall Combined Cohorts: Terminal Elimination Half-Life (t1/2) for Amivantamab
timeFrame: 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)
measure: Apparent Clearance at Steady State (CLss) of Amivantamab
timeFrame: 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)
measure: Apparent Volume of Distribution at Steady State (Vss) of Amivantamab
timeFrame: 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)
measure: Accumulation Ratio (AR) of AUCtau for Amivantamab
timeFrame: 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)
measure: Number of Participants With Anti-Amivantamab Antibodies
timeFrame: From start of the treatment (Day 1) up to 30 days after the last dose of study drug (up to 9 months)
Other outcomes:
Locations:
city: Chuo Ku
country: Japan
facility: National Cancer Center Hospital
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
city: Kitaadachi-gun
country: Japan
facility: Saitama Cancer center
city: Niigata
country: Japan
facility: Niigata Cancer Center Hospital
city: Sapporo-shi
country: Japan
facility: Hokkaido University Hospital
city: Sendai
country: Japan
facility: Tohoku University Hospital
city: Suita-shi
country: Japan
facility: Osaka University Hospital
city: Tokyo
country: Japan
facility: Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital
city: Tokyo
country: Japan
facility: The Cancer Institute Hospital of JFCR
city: Yokohama
country: Japan
facility: Yokohama City University Medical Center
Study officials:
affiliation: Janssen Pharmaceutical K.K.
name: Janssen Pharmaceutical K.K., Japan Clinical Trial
role: STUDY_DIRECTOR
References: