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

Gastric and Gastroesophageal Junction Adenocarcinoma Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04260191
• Other study ID #: 20180292
• Status: Terminated
• Phase: Phase 1
• Start date: June 29, 2020
• Est. completion date: June 2, 2022

Study information

• Verified date: April 2023
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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)

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 15
• Est. completion date: June 2, 2022
• Est. primary completion date: June 2, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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.

Related Conditions & MeSH terms

• Adenocarcinoma
• Esophageal Neoplasms
• Gastric and Gastroesophageal Junction Adenocarcinoma

Intervention

Drug:
• AMG 910
IV Infusion

Locations

Country	Name	City	State
Austria	Landeskrankenhaus Salzburg	Salzburg
France	Institut Gustave Roussy	Villejuif
Germany	Universitaetsklinikum Hamburg Eppendorf Onkologisches Zentrum	Hamburg
Germany	Universitätsklinikum Leipzig	Leipzig
Germany	Klinikum der Universität München Campus Grosshadern	München
Germany	Klinikum rechts der Isar	München
Japan	National Cancer Center Hospital	Chuo-ku	Tokyo
Japan	National Cancer Center Hospital East	Kashiwa-shi	Chiba
Japan	Aichi Cancer Center	Nagoya-shi	Aichi
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital Yonsei University Health System	Seoul
Netherlands	Amsterdam UMC - location VUmc	Amsterdam
Spain	Hospital Universitari Vall d Hebron	Barcelona	Cataluña
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
United States	City of Hope National Medical Center	Duarte	California
United States	University of California at Irvine Medical Center	Orange	California
United States	Wake Forest Baptist Health	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Austria,  France,  Germany,  Japan,  Korea, Republic of,  Netherlands,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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)
Secondary	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)
Secondary	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
Secondary	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
Secondary	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	PFS Per iRECIST	Data was not collected due to early termination of study, therefore data are not available.	6 months and 1 year
Secondary	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

External Links

•   AmgenTrials clinical trials website