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

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)

Study Overview

• Status: Terminated
• Conditions: Gastric and Gastroesophageal Junction Adenocarcinoma
• Intervention / Treatment: Drug: AMG 910

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• Austria
  • Salzburg, Austria, 5020
    • Landeskrankenhaus Salzburg
• France
  • Villejuif, France, 94805
    • Institut Gustave Roussy
• Germany
  • Hamburg, Germany, 20246
    • Universitaetsklinikum Hamburg Eppendorf Onkologisches Zentrum
  • Leipzig, Germany, 04103
    • Universitatsklinikum Leipzig
  • München, Germany, 81377
    • Klinikum der Universität München Campus Großhadern
  • München, Germany, 81675
    • Klinikum rechts der Isar
• Japan
  • Aichi
    • Nagoya-shi, Aichi, Japan, 464-8681
      • Aichi Cancer Center
  • Chiba
    • Kashiwa-shi, Chiba, Japan, 277-8577
      • National Cancer Center Hospital East
  • Tokyo
    • Chuo-ku, Tokyo, Japan, 104-0045
      • National Cancer Center Hospital
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital Yonsei University Health System
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
• Netherlands
  • Amsterdam, Netherlands, 1081HV
    • Amsterdam UMC - location VUmc
• Spain
  • Cataluña
    • Barcelona, Cataluña, Spain, 08035
      • Hospital Universitari Vall d Hebron
• Taiwan
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital
  • Taipei, Taiwan, 11217
    • Taipei Veterans General Hospital
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope National Medical Center
    • Orange, California, United States, 92868
      • University of California at Irvine Medical Center
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: AMG 910 6.5 μg; For 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.	Drug: AMG 910; IV Infusion
Experimental: Cohort 1b: AMG 910 6.5 μg; For 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.	Drug: AMG 910; IV Infusion
Experimental: Cohort 2b: AMG 910 15 μg; For 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.	Drug: AMG 910; IV Infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Day 1 to Day 28
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.	Day 1 to 30 days post-last dose; maximum duration was 10.97 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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)
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.	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)
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.	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
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.	Cycle 1 Day 8 pre-infusion and Cycle 1 Day 22 pre-infusion
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.	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)
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).	Day 1 to end of study (EOS); maximum time on study was 18.76 months
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.	Day 1 to EOS; maximum time on study was 18.76 months
Duration of Response (DOR) Per RECIST 1.1	As no participants experienced an objective response, data were not available.	Day 1 to EOS; maximum time on study was 18.76 months
DOR Per iRECIST	Data was not collected due to early termination of study, therefore data are not available.	Day 1 to EOS; maximum time on study was 18.76 months
Time to Progression Per RECIST 1.1	Data was not collected due to early termination of study, therefore data are not available.	Day 1 to EOS; maximum time on study was 18.76 months
Time to Progression Per iRECIST	Data was not collected due to early termination of study, therefore data are not available.	Day 1 to EOS; maximum time on study was 18.76 months
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.	6 months and 1 year
PFS Per iRECIST	Data was not collected due to early termination of study, therefore data are not available.	6 months and 1 year
Overall Survival	Data was not collected due to limited follow up time due to study termination, therefore data are not available.	1 year and 2 years

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): June 29, 2020
• Primary Completion (Actual): June 2, 2022
• Study Completion (Actual): June 2, 2022

Study Registration Dates

• First Submitted: February 5, 2020
• First Submitted That Met QC Criteria: February 5, 2020
• First Posted (Actual): February 7, 2020

Study Record Updates

• Last Update Posted (Estimated): January 25, 2024
• Last Update Submitted That Met QC Criteria: April 24, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Head and Neck Neoplasms; Esophageal Diseases; Adenocarcinoma; Esophageal Neoplasms
• Other Study ID Numbers: 20180292

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
• IPD Sharing Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• IPD Sharing Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No