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Gastric and Gastroesophageal Junction AdenocarcinomaPhase 1NCT04260191

Study of AMG 910 in Subjects With CLDN18.2-Positive Gastric and Gastroesophageal Junction Adenocarcinoma

A Phase 1 study testing AMG 910 in people with Gastric and Gastroesophageal Junction Adenocarcinoma, run by Amgen at 20 sites in 9 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

To evaluate the safety and tolerability of AMG 910 in adult subjects, and to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) Read more about this study

Who is it for?
Ages 18 to 99 years
What is being tested?
AMG 910
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
20 sitesin 9 countries
Study dates
29 Jun 2020to 2 Jun 2022
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 99 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Subjects with histologically or cytologically confirmed metastatic or locally advanced unresectable gastric or GEJ adenocarcinoma positive for CLDN18.2.
  • Subjects should not be eligible for curative surgery and should have been refractory to or have relapsed after two or more prior lines of standard systemic therapy that included a platinum, a fluoropyrimidine, either a taxane or irinotecan, and an approved vascular endothelial growth factor receptor (VEGFR) antibody/tyrosine kinase inhibitor (TKI) and depending on country-specific standards and approvals.
  • For subjects eligible for human epidermal growth factor receptor 2 (HER2) directed therapy, prior systemic therapy should have included a HER2 targeting antibody approved for treatment of gastric cancer.
  • Subjects may also be included if the aforementioned therapeutic options were medically not appropriate for them. In these cases, the reason(s) why required prior therapies for gastric cancer were medically not appropriate should be documented in the subject's electronic case report form (eCRF).
  • For dose-expansion only: Subjects with at least 1 measurable lesion greater than or equal to 10mm which has not undergone biopsy within 3 months of screening scan. This lesion cannot be biopsied at any time during the study.
  • Subjects with stable condition and anti-coagulative therapy ongoing for at least 1 month, no obvious signs and symptoms of bleeding, and coagulation parameters are fulfilled.
  • Subjects should be able to use proton pump inhibitors.

Who cannot join

  • Any anticancer therapy or immunotherapy within 4 weeks of start of first dose (14 days for palliative radiation).
  • Untreated or symptomatic central nervous system (CNS) metastases, leptomeningeal disease, or spinal cord compression
  • Autoimmune disorders requiring chronic systemic steroid therapy or any other form of immunosuppressive therapy while on study, eg, ulcerative colitis, Crohn's disease, or any other gastrointestinal autoimmune disorder causing chronic nausea, vomiting, or diarrhea. Recent or current use of inhaled steroids or physiological substitution in case of adrenal insufficiency is not exclusionary.
  • Evidence or history within last 3 months of gastrointestinal inflammatory conditions not associated with the underlying cancer disease including gastrinomas, duodenitis, proven gastric ulcer, duodenal ulcer, pancreatitis, or subjects with recent gastric bleeding. Subjects may be included if the symptomatic/immunosuppressive treatment is discontinued more than 4 weeks prior to the first dose of AMG 910, symptoms have resolved, and gastroscopy does not indicate signs of active disease.
  • Subjects with inherited bleeding disorders (eg, Willebrand's disease, hemophilia A and other clotting factor deficiency) and subjects with known heparin-induced thrombocytopenia.
  • Subjects requiring non-steroidal anti-inflammatory drugs (NSAIDs) during study treatment. The NSAID(s) should be stopped within 7 days prior to start of treatment.

Trial locations and contacts

20 sites in 9 countries.

20 sites in 9 countries

Germany4 sites
  • Universitaetsklinikum Hamburg Eppendorf Onkologisches Zentrum

    Hamburg, 20246

  • Universitätsklinikum Leipzig

    Leipzig, 04103

  • Klinikum der Universität München Campus Grosshadern

    München, 81377

  • Klinikum rechts der Isar

    München, 81675

Other trials in Germany

South Korea4 sites
  • Seoul National University Hospital

    Seoul, 03080

  • Severance Hospital Yonsei University Health System

    Seoul, 03722

  • Asan Medical Center

    Seoul, 05505

  • Samsung Medical Center

    Seoul, 06351

Other trials in South Korea

United States3 sites
  • City of Hope National Medical Center

    Duarte, California, 91010

  • University of California at Irvine Medical Center

    Orange, California, 92868

  • Wake Forest Baptist Health

    Winston-Salem, North Carolina, 27157

Other trials in United States

Japan3 sites
  • National Cancer Center Hospital

    Chuo-ku, Tokyo, 104-0045

  • National Cancer Center Hospital East

    Kashiwa-shi, Chiba, 277-8577

  • Aichi Cancer Center

    Nagoya, Aichi-ken, 464-8681

Other trials in Japan

Taiwan2 sites
  • National Taiwan University Hospital

    Taipei, 10002

  • Taipei Veterans General Hospital

    Taipei, 11217

Other trials in Taiwan

Austria1 site
  • Landeskrankenhaus Salzburg

    Salzburg, 5020

Other trials in Austria

France1 site
  • Institut Gustave Roussy

    Villejuif, 94805

Other trials in France

Netherlands1 site
  • Amsterdam UMC - location VUmc

    Amsterdam, 1081HV

Other trials in Netherlands

Spain1 site
  • Hospital Universitari Vall d Hebron

    Barcelona, Catalonia, 08035

Other trials in Spain

About this study

Official title: A Global Phase 1 Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of the Half-life Extended Bispecific T-cell Engager AMG 910 in Subjects With Claudin 18.2-Positive Gastric and Gastroesophageal Junction Adenocarcinoma

To evaluate the safety and tolerability of AMG 910 in adult subjects, and to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D)

Being tested
AMG 910

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AMG 910Drug

    IV Infusion

Study groups in NCT04260191
Study groupRoleWhat they receive
Cohort 1: AMG 910 6.5 μgExperimentalFor Cycles 1 and 2, participants received AMG 910 as a short-term intravenous (IV) infusion (approximately 60 minutes) at a dose of 6.5 μg twice a week on Days 1 and 3 of each week in a 28-day cycle. For Cycles 3 to 6, participants received AMG 910 as a short-term IV infusion (approximately 60 minutes) at a dose of 6.5 μg weekly, ie, Days 1, 8, 15 and 22 in a 28-day cycle.
Receives: Drug: AMG 910
Cohort 1b: AMG 910 6.5 μgExperimentalFor Cycle 1 Week 1, participants received AMG 910 as an extended IV (eIV) infusion (approximately 96 hours) at a dose of 6.5 μg. For the remainder of Cycles 1 and 2, participants received AMG 910 as a short-term IV infusion (approximately 60 minutes) at a dose of 6.5 μg twice a week on Days 1 and 3 of each week in a 28-day cycle. For Cycles 3 to 6, participants received AMG 910 as a short-term IV infusion (approximately 60 minutes) at a dose of 6.5 μg weekly, ie, Days 1, 8, 15 and 22 in a 28-day cycle.
Receives: Drug: AMG 910
Cohort 2b: AMG 910 15 μgExperimentalFor Cycle 1 Week 1, participants received AMG 910 as an eIV infusion (approximately 96 hours) at a dose of 15 μg. For the remainder of Cycles 1 and 2, participants received AMG 910 as a short-term IV infusion (approximately 60 minutes) at a dose of 15 μg twice a week on Days 1 and 3 of each week in a 28-day cycle. For Cycles 3 to 6, participants received AMG 910 as a short-term IV infusion (approximately 60 minutes) at a dose of 15 μg weekly, ie, Days 1, 8, 15 and 22 in a 28-day cycle.
Receives: Drug: AMG 910

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT)

    All DLTs were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. DLTs were defined as any AEs at least possibly related to AMG 910 with an onset within the first 28 days following first dose with any of the following:

    • Grade 2 gastric perforation or fistula
    • Grade ≥ 3 non-hematologic AEs including laboratory abnormalities
    • Re-challenge with AMG 910 after treatment interruption due to any stomach toxicity results in at least same stomach toxicity and is of CTCAE grade ≥ 3 or grade 2 and ongoing for more than 3 days despite optimal supportive treatment
    • Grade 4 thrombocytopenia or grade 3 thrombocytopenia with bleeding
    • Grade 4 neutropenia lasting > 28 days
    • Febrile neutropenia of any grade
    • Anemia requiring transfusion per local or international guidelines in the absence of bleeding
    • Grade 5 toxicity
    • Any other toxicity related to AMG 910 considered significant enough to be qualified as DLT in the opinion of the investigator

    Measured: Day 1 to Day 28

  2. Number of Participants Who Experienced a Treatment-emergent AE (TEAE)

    A TEAE was defined as any adverse event starting on or after the first administration of investigational product, as determined by the flag indicating if the adverse event started prior to the first dose on the Events case report form, and up to and including 30 days after the last investigational product dose date.

    Evaluation of TEAEs included the number of participants with at least 1 TEAE or treatment-related TEAE. Clinically significant changes in vital signs, electrocardiogram (ECG) and clinical laboratory tests were recorded as TEAEs.

    Measured: Day 1 to 30 days post-last dose; maximum duration was 10.97 months

Secondary outcomes (14)
  1. Maximum Serum Concentration (Cmax) of AMG 910

    Mean Cmax values for the dosing intervals following short-term IV infusion (Cohort 1) and following extended IV infusions (Cohorts 1b and 2b) for Cycle 1 Week 1, and for short-term IV infusions in subsequent dosing intervals in Cycle 1. The timing of the pharmacokinetic (PK) sampling for Week 1 (Days 1 - 7) was based on hours after the start of the infusion and from Day 8 onwards was based on hours after the end of infusion (EOI). Due to the limited number of samples obtained and early termination of the study, PK data are summarized for Cycle 1 only.

    Measured: Cycle 1: Days 1-7 at pre-infusion, 1, 2, 4, 24, 48, 72, 96, 120 and 144 hr; Days 8 and 10* at pre-infusion, EOI, 4 and 24 hr post-EOI; Days 15, 17* and 22* at pre-infusion and EOI; Day 24* at pre-infusion, EOI, 2, 4 and 24 hr post-EOI (*=Cohort 1 only)

  2. Minimum Serum Concentration (Ctrough) of AMG 910

    Mean Ctrough values for the dosing intervals following short-term IV infusion (Cohort 1) and following extended IV infusions (Cohorts 1b and 2b) for Cycle 1 Week 1, and for short-term IV infusions in subsequent dosing intervals in Cycle 1 are presented. The timing of the PK sampling for Week 1 (Days 1-7) was based on hours after the start of infusion and from Day 8 onwards was based on hours after EOI. Due to the limited number of samples obtained and early termination of the study, PK data are summarized for Cycle 1 only.

    Measured: Cycle 1: Days 1-7 at pre-infusion, 1, 2, 4, 24, 48, 72, 96, 120 and 144 hr; Days 8 and 10* at pre-infusion, EOI, 4 and 24 hr post-EOI; Days 15, 17* and 22* at pre-infusion and EOI; Day 24* at pre-infusion, EOI, 2, 4 and 24 hr post-EOI (*=Cohort 1 only)

  3. Area Under the Concentration-time Curve (AUC) Over the Dosing Interval (AUC0_168hr)

    The timing of the PK sampling for Week 1 (Days 1-7) was based on hours after the start of infusion, and for Day 8 after EOI.

    Measured: Cycle 1 Day 1 at pre-infusion, 1, 2, 4, 24, 48, 72, 96, 120 and 144 hr after infusion start and Cycle 1 Day 8 pre-infusion through 168 hr post-EOI

  4. Cohort 1 Only: Accumulation Ratio (AR) of AMG 910

    Calculated as AR = Cycle 1 Day 22 pre-infusion concentration/Cycle 1 Day 8 pre-infusion concentration.

    Measured: Cycle 1 Day 8 pre-infusion and Cycle 1 Day 22 pre-infusion

  5. Half-life (t1/2) of AMG 910

    Mean t1/2 values for the dosing intervals following short-term IV infusion (Cohort 1) and following extended IV infusions (Cohorts 1b and 2b) for Cycle 1 Week 1, and for short-term IV infusions in subsequent dosing intervals in Cycle 1 are presented. The timing of the PK sampling for Week 1 (Days 1-7) was based on hours after the start of infusion and from Day 8 onwards was based on hours after EOI. Due to the limited number of samples obtained and early termination of the study, PK data are summarized for Cycle 1 only.

    Measured: Cycle 1: Days 1-7 at pre-infusion, 1, 2, 4, 24, 48, 72, 96, 120 and 144 hr; Days 8 and 10* at pre-infusion, EOI, 4 and 24 hr post-EOI (*=Cohort 1 only)

  6. Number of Participants With an Objective Response (OR) Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

    OR was defined as a best overall response (BOR) of complete response (CR) or partial response (PR) per RECIST v1.1:

    • CR: Disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have had a reduction in short axis to < 10 mm.
    • PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Non target lesions must be non-progressive Disease (non-PD).

    Measured: Day 1 to end of study (EOS); maximum time on study was 18.76 months

  7. ORR Per Immune RECIST (iRECIST)

    ORR was defined as the incidence of a BOR of immune complete response (iCR) or immune partial response (iPR) per iRECIST:

    • iCR: Disappearance of all non-nodal target and non-target lesions and normalization of pathological lymph nodes (whether target or non-target) to <10 mm in short axis.
    • iPR: At least a 30% decrease in the sum of measures of target lesions, taking as reference the baseline target lesion sum.

    Data was not collected due to early termination of study, therefore data are not available.

    Measured: Day 1 to EOS; maximum time on study was 18.76 months

  8. Duration of Response (DOR) Per RECIST 1.1

    As no participants experienced an objective response, data were not available.

    Measured: Day 1 to EOS; maximum time on study was 18.76 months

  9. DOR Per iRECIST

    Data was not collected due to early termination of study, therefore data are not available.

    Measured: Day 1 to EOS; maximum time on study was 18.76 months

  10. Time to Progression Per RECIST 1.1

    Data was not collected due to early termination of study, therefore data are not available.

    Measured: Day 1 to EOS; maximum time on study was 18.76 months

  11. Time to Progression Per iRECIST

    Data was not collected due to early termination of study, therefore data are not available.

    Measured: Day 1 to EOS; maximum time on study was 18.76 months

  12. Progression-free Survival (PFS) Per RECIST 1.1

    Data was not collected due to limited follow up time due to study termination, therefore data are not available.

    Measured: 6 months and 1 year

  13. PFS Per iRECIST

    Data was not collected due to early termination of study, therefore data are not available.

    Measured: 6 months and 1 year

  14. Overall Survival

    Data was not collected due to limited follow up time due to study termination, therefore data are not available.

    Measured: 1 year and 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Feb 2020
  2. Study start29 Jun 2020
  3. Primary completion2 Jun 2022
  4. Study completion2 Jun 2022

Why it stopped: Business Decision

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04260191
Sponsor's protocol ID
20180292
Status last verified
Apr 2023
First submitted
5 Feb 2020
Last updated
25 Jan 2024
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing AMG 910 in people with Gastric and Gastroesophageal Junction Adenocarcinoma, run by Amgen at 20 sites in 9 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 25 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 20 sites in Germany, South Korea, United States, Japan, Taiwan and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Jan 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) (time frame: Day 1 to Day 28). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jan 2024.

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