Gastric and Gastroesophageal Junction Adenocarcinoma
Conditions
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)
Interventions
DRUGAMG 910
IV Infusion
Sponsors
Amgen
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | Day 1 to Day 28 | 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 |
| Number of Participants Who Experienced a Treatment-emergent AE (TEAE) | Day 1 to 30 days post-last dose; maximum duration was 10.97 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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. |
| Cohort 1 Only: Accumulation Ratio (AR) of AMG 910 | Cycle 1 Day 8 pre-infusion and Cycle 1 Day 22 pre-infusion | Calculated as AR = Cycle 1 Day 22 pre-infusion concentration/Cycle 1 Day 8 pre-infusion concentration. |
| 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) | 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. |
| Number of Participants With an Objective Response (OR) Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 | Day 1 to end of study (EOS); maximum time on study was 18.76 months | 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 Per Immune RECIST (iRECIST) | Day 1 to EOS; maximum time on study was 18.76 months | 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. |
| Duration of Response (DOR) Per RECIST 1.1 | Day 1 to EOS; maximum time on study was 18.76 months | As no participants experienced an objective response, data were not available. |
| 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) | 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. |
| Time to Progression Per RECIST 1.1 | Day 1 to EOS; maximum time on study was 18.76 months | Data was not collected due to early termination of study, therefore data are not available. |
| Time to Progression Per iRECIST | Day 1 to EOS; maximum time on study was 18.76 months | Data was not collected due to early termination of study, therefore data are not available. |
| Progression-free Survival (PFS) Per RECIST 1.1 | 6 months and 1 year | Data was not collected due to limited follow up time due to study termination, therefore data are not available. |
| PFS Per iRECIST | 6 months and 1 year | Data was not collected due to early termination of study, therefore data are not available. |
| Overall Survival | 1 year and 2 years | Data was not collected due to limited follow up time due to study termination, therefore data are not available. |
| DOR Per iRECIST | Day 1 to EOS; maximum time on study was 18.76 months | Data was not collected due to early termination of study, therefore data are not available. |
| 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) | 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. |
Countries
Austria, France, Germany, Japan, Netherlands, South Korea, Spain, Taiwan, United States
Participant flow
Recruitment details
A total of 15 participants were enrolled and received AMG 910 at 10 centers in Europe, South Korea, Taiwan and the United States between 29 June 2020 and 02 June 2022.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 6 |
| 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 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. | 4 |
| 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 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. | 5 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 4 | 3 | 2 |
| Overall Study | Decision by Sponsor | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 3 |
Baseline characteristics
| Characteristic | Total | Cohort 1: AMG 910 6.5 µg | Cohort 1b: AMG 910 6.5 µg | Cohort 2b: AMG 910 15 µg |
|---|---|---|---|---|
| Age, Continuous | 57.9 years STANDARD_DEVIATION 15.6 | 55.5 years STANDARD_DEVIATION 14.9 | 54.3 years STANDARD_DEVIATION 22.9 | 63.6 years STANDARD_DEVIATION 10.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants | 6 Participants | 3 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 4 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 8 Participants | 4 Participants | 2 Participants | 2 Participants |
| Sex: Female, Male Female | 4 Participants | 2 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 11 Participants | 4 Participants | 3 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 4 / 6 | 3 / 4 | 2 / 5 |
| other Total, other adverse events | 6 / 6 | 4 / 4 | 5 / 5 |
| serious Total, serious adverse events | 4 / 6 | 3 / 4 | 2 / 5 |
Outcome results
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
Time frame: Day 1 to Day 28
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: AMG 910 6.5 µg | Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | 2 Participants |
| Cohort 1b: AMG 910 6.5 µg | Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | 0 Participants |
| Cohort 2b: AMG 910 15 µg | Number of Participants Who Experienced a Dose-Limiting Toxicity (DLT) | 1 Participants |
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.
Time frame: Day 1 to 30 days post-last dose; maximum duration was 10.97 months
Population: Safety Analysis Set: All participants that were enrolled and received at least 1 dose of AMG 910.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: AMG 910 6.5 µg | Number of Participants Who Experienced a Treatment-emergent AE (TEAE) | TEAEs | 6 Participants |
| Cohort 1: AMG 910 6.5 µg | Number of Participants Who Experienced a Treatment-emergent AE (TEAE) | Treatment-related TEAEs | 4 Participants |
| Cohort 1b: AMG 910 6.5 µg | Number of Participants Who Experienced a Treatment-emergent AE (TEAE) | Treatment-related TEAEs | 4 Participants |
| Cohort 1b: AMG 910 6.5 µg | Number of Participants Who Experienced a Treatment-emergent AE (TEAE) | TEAEs | 4 Participants |
| Cohort 2b: AMG 910 15 µg | Number of Participants Who Experienced a Treatment-emergent AE (TEAE) | Treatment-related TEAEs | 5 Participants |
| Cohort 2b: AMG 910 15 µg | Number of Participants Who Experienced a Treatment-emergent AE (TEAE) | TEAEs | 5 Participants |
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.
Time frame: 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
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: AMG 910 6.5 µg | Area Under the Concentration-time Curve (AUC) Over the Dosing Interval (AUC0_168hr) | 359 hr•ng/mL | Standard Deviation 262 |
| Cohort 1b: AMG 910 6.5 µg | Area Under the Concentration-time Curve (AUC) Over the Dosing Interval (AUC0_168hr) | 251 hr•ng/mL | Standard Deviation 98.6 |
| Cohort 2b: AMG 910 15 µg | Area Under the Concentration-time Curve (AUC) Over the Dosing Interval (AUC0_168hr) | 1710 hr•ng/mL | Standard Deviation 1160 |
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.
Time frame: Cycle 1 Day 8 pre-infusion and Cycle 1 Day 22 pre-infusion
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: AMG 910 6.5 µg | Cohort 1 Only: Accumulation Ratio (AR) of AMG 910 | 1.48 ratio |
Secondary
DOR Per iRECIST
Data was not collected due to early termination of study, therefore data are not available.
Time frame: Day 1 to EOS; maximum time on study was 18.76 months
Population: Data were not collected.
Secondary
Duration of Response (DOR) Per RECIST 1.1
As no participants experienced an objective response, data were not available.
Time frame: Day 1 to EOS; maximum time on study was 18.76 months
Population: 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.
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.
Time frame: 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)
Population: 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.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Cohort 1: AMG 910 6.5 µg | Half-life (t1/2) of AMG 910 | Cycle 1 Day 10 | 45.6 hr |
| Cohort 1: AMG 910 6.5 µg | Half-life (t1/2) of AMG 910 | Cycle 1 Day 3 | 47.4 hr |
| Cohort 1b: AMG 910 6.5 µg | Half-life (t1/2) of AMG 910 | Cycle 1 Day 7 | 39.3 hr |
| Cohort 1b: AMG 910 6.5 µg | Half-life (t1/2) of AMG 910 | Cycle 1 Day 8 | 63.2 hr |
| Cohort 2b: AMG 910 15 µg | Half-life (t1/2) of AMG 910 | Cycle 1 Day 8 | 66.9 hr |
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.
Time frame: 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)
Population: 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.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Cohort 1: AMG 910 6.5 µg | Maximum Serum Concentration (Cmax) of AMG 910 | Cycle 1 Day 17 | 2.17 ng/mL |
| Cohort 1: AMG 910 6.5 µg | Maximum Serum Concentration (Cmax) of AMG 910 | Cycle 1 Day 24 | 2.38 ng/mL |
| Cohort 1: AMG 910 6.5 µg | Maximum Serum Concentration (Cmax) of AMG 910 | Cycle 1 Day 1 | 3.78 ng/mL |
| Cohort 1: AMG 910 6.5 µg | Maximum Serum Concentration (Cmax) of AMG 910 | Cycle 1 Day 3 | 5.89 ng/mL |
| Cohort 1: AMG 910 6.5 µg | Maximum Serum Concentration (Cmax) of AMG 910 | Cycle 1 Day 8 | 2.92 ng/mL |
| Cohort 1: AMG 910 6.5 µg | Maximum Serum Concentration (Cmax) of AMG 910 | Cycle 1 Day 10 | 3.62 ng/mL |
| Cohort 1: AMG 910 6.5 µg | Maximum Serum Concentration (Cmax) of AMG 910 | Cycle 1 Day 15 | 1.82 ng/mL |
| Cohort 1: AMG 910 6.5 µg | Maximum Serum Concentration (Cmax) of AMG 910 | Cycle 1 Day 22 | 2.22 ng/mL |
| Cohort 1b: AMG 910 6.5 µg | Maximum Serum Concentration (Cmax) of AMG 910 | Cycle 1 Day 8 | 13.6 ng/mL |
| Cohort 1b: AMG 910 6.5 µg | Maximum Serum Concentration (Cmax) of AMG 910 | Cycle 1 Day 7 | 2.91 ng/mL |
| Cohort 1b: AMG 910 6.5 µg | Maximum Serum Concentration (Cmax) of AMG 910 | Cycle 1 Day 15 | 4.99 ng/mL |
| Cohort 2b: AMG 910 15 µg | Maximum Serum Concentration (Cmax) of AMG 910 | Cycle 1 Day 7 | 15.8 ng/mL |
| Cohort 2b: AMG 910 15 µg | Maximum Serum Concentration (Cmax) of AMG 910 | Cycle 1 Day 8 | 22.3 ng/mL |
| Cohort 2b: AMG 910 15 µg | Maximum Serum Concentration (Cmax) of AMG 910 | Cycle 1 Day 15 | 10.5 ng/mL |
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.
Time frame: 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)
Population: 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.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Cohort 1: AMG 910 6.5 µg | Minimum Serum Concentration (Ctrough) of AMG 910 | Cycle 1 Day 3 | 0.698 ng/mL |
| Cohort 1: AMG 910 6.5 µg | Minimum Serum Concentration (Ctrough) of AMG 910 | Cycle 1 Day 10 | 0.979 ng/mL |
| Cohort 1: AMG 910 6.5 µg | Minimum Serum Concentration (Ctrough) of AMG 910 | Cycle 1 Day 15 | 0.836 ng/mL |
| Cohort 1: AMG 910 6.5 µg | Minimum Serum Concentration (Ctrough) of AMG 910 | Cycle 1 Day 17 | 0.664 ng/mL |
| Cohort 1: AMG 910 6.5 µg | Minimum Serum Concentration (Ctrough) of AMG 910 | Cycle 1 Day 22 | 1.05 ng/mL |
| Cohort 1: AMG 910 6.5 µg | Minimum Serum Concentration (Ctrough) of AMG 910 | Cycle 1 Day 1 | 0.952 ng/mL |
| Cohort 1: AMG 910 6.5 µg | Minimum Serum Concentration (Ctrough) of AMG 910 | Cycle 1 Day 24 | 0.540 ng/mL |
| Cohort 1: AMG 910 6.5 µg | Minimum Serum Concentration (Ctrough) of AMG 910 | Cycle 1 Day 8 | 1.48 ng/mL |
| Cohort 1b: AMG 910 6.5 µg | Minimum Serum Concentration (Ctrough) of AMG 910 | Cycle 1 Day 7 | 0.813 ng/mL |
| Cohort 1b: AMG 910 6.5 µg | Minimum Serum Concentration (Ctrough) of AMG 910 | Cycle 1 Day 8 | 1.54 ng/mL |
| Cohort 1b: AMG 910 6.5 µg | Minimum Serum Concentration (Ctrough) of AMG 910 | Cycle 1 Day 15 | 1.02 ng/mL |
| Cohort 2b: AMG 910 15 µg | Minimum Serum Concentration (Ctrough) of AMG 910 | Cycle 1 Day 7 | 7.27 ng/mL |
| Cohort 2b: AMG 910 15 µg | Minimum Serum Concentration (Ctrough) of AMG 910 | Cycle 1 Day 15 | 2.54 ng/mL |
| Cohort 2b: AMG 910 15 µg | Minimum Serum Concentration (Ctrough) of AMG 910 | Cycle 1 Day 8 | 3.70 ng/mL |
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).
Time frame: Day 1 to end of study (EOS); maximum time on study was 18.76 months
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: AMG 910 6.5 µg | Number of Participants With an Objective Response (OR) Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 | 0 Participants |
| Cohort 1b: AMG 910 6.5 µg | Number of Participants With an Objective Response (OR) Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 | 0 Participants |
| Cohort 2b: AMG 910 15 µg | Number of Participants With an Objective Response (OR) Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 | 0 Participants |
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.
Time frame: Day 1 to EOS; maximum time on study was 18.76 months
Population: Data were not collected.
Secondary
Overall Survival
Data was not collected due to limited follow up time due to study termination, therefore data are not available.
Time frame: 1 year and 2 years
Population: Data were not collected.
Secondary
PFS Per iRECIST
Data was not collected due to early termination of study, therefore data are not available.
Time frame: 6 months and 1 year
Population: Data were not collected.
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.
Time frame: 6 months and 1 year
Population: Data were not collected.
Secondary
Time to Progression Per iRECIST
Data was not collected due to early termination of study, therefore data are not available.
Time frame: Day 1 to EOS; maximum time on study was 18.76 months
Population: Data were not collected.
Secondary
Time to Progression Per RECIST 1.1
Data was not collected due to early termination of study, therefore data are not available.
Time frame: Day 1 to EOS; maximum time on study was 18.76 months
Population: Data were not collected.