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

NCT04260191 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: 20180292
• Study Type: interventional
• Target: 15
• Locations: 9 countries
• Sites: 20

Brief 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)

Conditions

Gastric and Gastroesophageal Junction Adenocarcinoma

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (14)

• Maximum Serum Concentration (Cmax) of AMG 910

  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

  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)

  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

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

• Half-life (t1/2) of AMG 910

  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)

Study Arms (3)

Cohort 1: AMG 910 6.5 μg

EXPERIMENTAL

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

Cohort 1b: AMG 910 6.5 μg

EXPERIMENTAL

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

Cohort 2b: AMG 910 15 μg

EXPERIMENTAL

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

Interventions

AMG 910 DRUG

IV Infusion

Cohort 1: AMG 910 6.5 μg; Cohort 1b: AMG 910 6.5 μg; Cohort 2b: AMG 910 15 μg

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Amgen: lead

Study Sites (20)

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

University of California at Irvine Medical Center

Orange, California, 92868, United States

Location

Wake Forest Baptist Health

Winston-Salem, North Carolina, 27157, United States

Location

Landeskrankenhaus Salzburg

Salzburg, 5020, Austria

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

Universitaetsklinikum Hamburg Eppendorf Onkologisches Zentrum

Hamburg, 20246, Germany

Location

Universitätsklinikum Leipzig

Leipzig, 04103, Germany

Location

Klinikum der Universität München Campus Grosshadern

München, 81377, Germany

Location

Klinikum rechts der Isar

München, 81675, Germany

Location

Aichi Cancer Center

Nagoya, Aichi-ken, 464-8681, Japan

Location

National Cancer Center Hospital East

Kashiwa-shi, Chiba, 277-8577, Japan

Location

National Cancer Center Hospital

Chuo-ku, Tokyo, 104-0045, Japan

Location

Amsterdam UMC - location VUmc

Amsterdam, 1081HV, Netherlands

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital Yonsei University Health System

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Hospital Universitari Vall d Hebron

Barcelona, Catalonia, 08035, Spain

Location

National Taiwan University Hospital

Taipei, 10002, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

Location

Related Links

• AmgenTrials clinical trials website

Limitations and Caveats

The study was discontinued due to a strategic decision to end clinical development for AMG 910 that was unrelated to safety.

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2020
• First Posted: February 7, 2020
• Study Start: June 29, 2020
• Primary Completion: June 2, 2022
• Study Completion: June 2, 2022
• Last Updated: January 25, 2024
• Results First Posted: January 25, 2024

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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.
• 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.

Locations

AU (1); US (3); FR (1); JP (3); ES (1); DE (4); NL (1); TW (2); KR (4)