Neoplasms

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Digestive System Diseases

Rare Diseases

Adenocarcinoma

Esophageal Neoplasms

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Gastrointestinal Neoplasms

Digestive System Neoplasms

Head and Neck Neoplasms

Gastrointestinal Diseases

Esophageal Diseases

Esophageal Cancer

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.

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.

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.

AMG 910

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 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

De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request

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

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.

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.

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.

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.

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

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.

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).

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.

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

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

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

Amgen

For all-cause mortality, time frame is from enrollment through end of study including long term follow-up. For SAE and non-serious AEs, time frame is treatment emergent.

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.

Cohort 1: 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 Cycle 1 (from Day 8) and for Cycles 2 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.

Cohort 1b: AMG 910 6.5 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 Cycle 1 (from Day 8) and for Cycles 2 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.

Cohort 2b: AMG 910 15 µg

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race/Ethnicity, Customized

Safety Analysis Set: All participants that were enrolled and received at least 1 dose of AMG 910.

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

Study Director

Safety Analysis Set: All participants that were enrolled and received at least 1 dose of AMG 910. Only participants who received study treatment (at least 80% of the planned dose for Cycle 1) and remained on study through the DLT assessment window were considered DLT-evaluable.

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

TEAEs

Treatment-related TEAEs

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

Cycle 1 Day 1

Cycle 1 Day 3

Cycle 1 Day 7

Cycle 1 Day 8

Cycle 1 Day 10

Cycle 1 Day 15

Cycle 1 Day 17

Cycle 1 Day 22

Cycle 1 Day 24

PK Analysis Set: Includes all participants who have received at least 1 dose of the AMG 910 and have at least 1 PK sample collected. Participants with data available at each time point are included.

Maximum Serum Concentration (Cmax) of AMG 910

Minimum Serum Concentration (Ctrough) of AMG 910

PK Analysis Set: Includes all participants who have received at least 1 dose of the AMG 910 and have at least 1 PK sample collected. Participants with data available are included.

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

PK Analysis Set: Includes all participants who have received at least 1 dose of the AMG 910 and have at least 1 PK sample collected. Participants with data available at both time points are included.

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

Half-life (t1/2) of AMG 910

RECIST Evaluable Analysis Set: Included all participants that were enrolled and received at least 1 dose of AMG 910 with at least 1 tumor lesion that was measurable in contrast-enhanced computed tomography (CT) as defined by RECIST 1.1 at baseline.

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

ORR Per Immune RECIST (iRECIST)

RECIST Evaluable Analysis Set: Included all participants that were enrolled and received at least 1 dose of AMG 910 with at least 1 tumor lesion that was measurable in contrast-enhanced CT as defined by RECIST 1.1 at baseline.

Spots Global Cancer Trial Database for Study of AMG 910 in Subjects With CLDN18.2-Positive Gastric and Gastroesophageal Junction Adenocarcinoma

Trial Identification

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Study Description

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