Colorectal Cancer, Locally Advanced, Metastatic Cancer, Non-Small Cell Lung Cancer, Ovarian Cancer, Pancreatic Cancer, Sarcoma, Solid Tumors
Conditions
Keywords
AMG 655, AMG 479, Apoptosis, Monoclonal Antibody, Tumor Necrosis Factor, Insulin-like Growth Factor
Brief summary
This is a multi-center, 2-part phase 1b/2 study of AMG 655 in combination with AMG 479 to be conducted in the United States and Spain. Part 1 is a dose escalation segment to identify a dose of AMG 655 in combination with AMG 479 that is safe and tolerable. Part 2 will evaluate the safety and estimate the efficacy of AMG 655 at the dose selected in Part 1 in combination with AMG 479 for the treatment of patients with advanced NSCLC (non-squamous histology; squamous histology), CRC, pancreatic cancer, ovarian cancer, and sarcoma.
Interventions
Sponsors
NantCell, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Part 1: Histologically or cytologically confirmed, locally advanced or metastatic, treatment-refractory solid tumors * Part 2: Histologically or cytologically confirmed, locally advanced or metastatic: NSCLC (squamous or non-squamous cell carcinoma; up to 2 prior treatment regimens), Colorectal Cancer (up to 2 prior treatment regimens), Pancreatic Cancer (up to 1 prior treatment regimen), Ovarian cancer (up to 2 prior treatment regimens), or Sarcoma (up to 2 prior treatment regimens), according to cohort availability * Eastern Cooperative Group (ECOG performance status of 0 or 1 * Women or men ≥16 years of age * Adequate hematology, renal, hepatic, coagulation and glycemic function.
Exclusion criteria
* Presence of uncontrolled central nervous system (CNS) disease * Systemic chemotherapy, hormonal therapy, immunotherapy, experimental or approved anticancer proteins/antibodies therapy ≤28 days before enrollment. * Prior treatment with death receptor agonists (including but not limited to rhApo2L/TRAIL \[AMG951\], apomab, mapatumumab, lexatumumab, CS-1008) * Prior treatment with IGF receptor antagonists (including but not limited to CP-751, 871, MK0646, AVE1642 or IMC-A12)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose-limiting Toxicities | Time from first dose up to 24 months | Incidence of adverse events and clinical laboratory abnormalities defined as DLTs. Dose-limiting toxicities included any grade 3 or higher hematologic or nonhematologic toxicity related to conatumumab or the combination of conatumumab with ganitumab except for lymphocytopenia and anemia. |
| Objective Response Rate | Time from first dose up to 24 months | The objective response rate (ORR) is defined as confirmed complete response or partial response using modified Response Evaluation Criteria in Solid Tumors \[RECIST\]: a complete response is the disappearance of all target lesions; a partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To Evaluate the Concentration Level of AMG 655 | Cycle 1 Day 1 end of infusion; Cycle 3 Day 1 end of infusion (each cycle is 28 days, each infusion is up to 1 hour) | Median, minimum, and maximum concentration of AMG 655 at specified time points. |
| To Evaluate the Concentration Level of AMG 479 | Cycle 1 Day 1 end of infusion; Cycle 3 Day 1 end of infusion (each cycle is 28 days, each infusion is up to 1 hour) | Median, minimum, and maximum concentration of AMG 479 at specified time points. |
| Progression Free Survival | Time from first dose up to 24 months | Progression-free survival is defined as the number of days from study day 1 (first dose of investigational product) to the first observation of disease progression (by modified RECIST; or clinical progression, whichever came first) or death due to any cause. Disease progression by RECIST is defined as at least a 20% increase in the sum of diameters of target lesions in reference to the smallest sum on study and an absolute increase of at least 5 mm; the appearance of any new lesions is also considered progression. |
| Duration of Response | Time from objective response to 24 months | Duration of response is defined as the number of days between the date of first objective response to the time of the first progressive disease (per modified Response Evaluation Criteria in Solid Tumors \[RECIST\] or clinical progression, whichever occurs first) or death due to any cause. Objective response is defined as a tumor response assessment of either complete response or partial response per modified RECIST where a complete response is the disappearance of all target lesions and a partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Per RECIST v 1.1, disease progression is defined as at least a 20% increase in the sum of diameters of target lesions in reference to the smallest sum on study and an absolute increase of at least 5 mm; the appearance of any new lesions is also considered progression. |
| Time to Response | Time from first dose up to 24 months | Time to response is the time from study day 1 to the first observation of an objective response. Subjects without an objective response are excluded from the analysis of this endpoint. Objective response is defined as a tumor response assessment of either complete response or partial response per modified Response Evaluation Criteria in Solid Tumors (RECIST) and will be determined based on the Investigator-reported assessment only for subjects with measurable disease at baseline. Per RECIST v 1.1: a complete response is the disappearance of all target lesions; a partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
| To Evaluate Anti-AMG 655 Antibody Formation and Anti-AMG 479 Antibody Formation | Time from first dose up to 24 months | — |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Part 1 Cohort 1 AMG 479 18 mg/kg IV plus AMG 655 1 mg/kg IV (day 1 of each Q3W cycle)
AMG 479: AMG 479 is an investigational, fully human, monoclonal antibody that binds with Insulin-like growth factor receptor type 1.
AMG 655: AMG 655 is an investigational, fully human, monoclonal antibody that binds with TNF-related apoptosis-inducing ligand, DR 5. | 3 |
| Part 1 Cohort 2 AMG 479 18 mg/kg IV plus AMG 655 3 mg/kg IV (day 1 of each Q3W cycle)
AMG 479: AMG 479 is an investigational, fully human, monoclonal antibody that binds with Insulin-like growth factor receptor type 1.
AMG 655: AMG 655 is an investigational, fully human, monoclonal antibody that binds with TNF-related apoptosis-inducing ligand, DR 5. | 3 |
| Part 1 Cohort 3 AMG 479 18 mg/kg IV plus AMG 655 15 mg/kg IV (day 1 of each Q3W cycle)
AMG 479: AMG 479 is an investigational, fully human, monoclonal antibody that binds with Insulin-like growth factor receptor type 1.
AMG 655: AMG 655 is an investigational, fully human, monoclonal antibody that binds with TNF-related apoptosis-inducing ligand, DR 5. | 3 |
| Part 2 Cohort 1 AMG 479 18 mg/kg (Q3W) with AMG 655 15 mg/kg (Q3W) Non-squamous NSCLC | 15 |
| Part 2 Cohort 2 AMG 479 18 mg/kg (Q3W) with AMG 655 15 mg/kg (Q3W) Squamous NSCLC | 8 |
| Part 2 Cohort 3 AMG 479 18 mg/kg (Q3W) with AMG 655 15 mg/kg (Q3W) CRC | 16 |
| Part 2 Cohort 4 AMG 479 18 mg/kg (Q3W) with AMG 655 15 mg/kg (Q3W) Pancreatic Cancer | 16 |
| Part 2 Cohort 5 AMG 479 18 mg/kg (Q3W) with AMG 655 15 mg/kg (Q3W) Ovarian Cancer | 9 |
| Part 2 Cohort 6 AMG 479 18 mg/kg (Q3W) with AMG 655 15 mg/kg (Q3W) Sarcoma | 16 |
| Total | 89 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Administrative Decision | 0 | 0 | 0 | 0 | 1 | 2 | 0 | 2 | 0 |
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Death | 1 | 1 | 3 | 8 | 5 | 7 | 9 | 4 | 7 |
| Overall Study | Ineligibility determined | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 2 | 0 | 1 | 0 | 6 | 2 | 2 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 0 | 0 | 1 | 1 | 1 | 5 | 1 | 4 |
Baseline characteristics
| Characteristic | Total | Part 1 Cohort 3 | Part 1 Cohort 2 | Part 1 Cohort 1 | Part 2 Cohort 3 | Part 2 Cohort 2 | Part 2 Cohort 1 | Part 2 Cohort 6 | Part 2 Cohort 5 | Part 2 Cohort 4 |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous Part 1 | 53.1 years STANDARD_DEVIATION 14.1 | 46.0 years STANDARD_DEVIATION 4.4 | 65.3 years STANDARD_DEVIATION 1.2 | 48.0 years STANDARD_DEVIATION 20.9 | — | — | — | — | — | — |
| Age, Continuous Part 2 | 58.8 years STANDARD_DEVIATION 11.1 | — | — | — | 59.1 years STANDARD_DEVIATION 11 | 67.0 years STANDARD_DEVIATION 7.3 | 61.0 years STANDARD_DEVIATION 10.3 | 51.3 years STANDARD_DEVIATION 9.8 | 58.0 years STANDARD_DEVIATION 15.8 | 60.2 years STANDARD_DEVIATION 8.8 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 73 Participants | 3 Participants | 3 Participants | 2 Participants | 13 Participants | 5 Participants | 12 Participants | 14 Participants | 8 Participants | 13 Participants |
| Sex: Female, Male Female | 44 Participants | 2 Participants | 1 Participants | 2 Participants | 5 Participants | 2 Participants | 8 Participants | 10 Participants | 9 Participants | 5 Participants |
| Sex: Female, Male Male | 43 Participants | 1 Participants | 2 Participants | 1 Participants | 11 Participants | 5 Participants | 7 Participants | 5 Participants | 0 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 3 | 1 / 3 | 3 / 3 | 8 / 15 | 5 / 8 | 7 / 16 | 9 / 16 | 4 / 9 | 7 / 16 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 3 / 3 | 15 / 15 | 7 / 7 | 15 / 16 | 14 / 16 | 9 / 9 | 11 / 15 |
| serious Total, serious adverse events | 2 / 3 | 0 / 3 | 2 / 3 | 3 / 15 | 6 / 7 | 2 / 16 | 3 / 16 | 3 / 9 | 2 / 15 |
Outcome results
Primary
Number of Participants With Dose-limiting Toxicities
Incidence of adverse events and clinical laboratory abnormalities defined as DLTs. Dose-limiting toxicities included any grade 3 or higher hematologic or nonhematologic toxicity related to conatumumab or the combination of conatumumab with ganitumab except for lymphocytopenia and anemia.
Time frame: Time from first dose up to 24 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1 Cohort 1 | Number of Participants With Dose-limiting Toxicities | 0 Participants |
| Part 1 Cohort 2 | Number of Participants With Dose-limiting Toxicities | 0 Participants |
| Part 1 Cohort 3 | Number of Participants With Dose-limiting Toxicities | 0 Participants |
Primary
Objective Response Rate
The objective response rate (ORR) is defined as confirmed complete response or partial response using modified Response Evaluation Criteria in Solid Tumors \[RECIST\]: a complete response is the disappearance of all target lesions; a partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: Time from first dose up to 24 months
Population: A subject was included in the analysis if they received at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1 Cohort 1 | Objective Response Rate | 1 Participants |
| Part 1 Cohort 2 | Objective Response Rate | 0 Participants |
| Part 1 Cohort 3 | Objective Response Rate | 0 Participants |
| Part 2 Cohort 1 | Objective Response Rate | 0 Participants |
| Part 2 Cohort 2 | Objective Response Rate | 0 Participants |
| Part 2 Cohort 3 | Objective Response Rate | 0 Participants |
| Part 2 Cohort 4 | Objective Response Rate | 0 Participants |
| Part 2 Cohort 5 | Objective Response Rate | 0 Participants |
| Part 2 Cohort 6 | Objective Response Rate | 0 Participants |
Secondary
Duration of Response
Duration of response is defined as the number of days between the date of first objective response to the time of the first progressive disease (per modified Response Evaluation Criteria in Solid Tumors \[RECIST\] or clinical progression, whichever occurs first) or death due to any cause. Objective response is defined as a tumor response assessment of either complete response or partial response per modified RECIST where a complete response is the disappearance of all target lesions and a partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Per RECIST v 1.1, disease progression is defined as at least a 20% increase in the sum of diameters of target lesions in reference to the smallest sum on study and an absolute increase of at least 5 mm; the appearance of any new lesions is also considered progression.
Time frame: Time from objective response to 24 months
Population: Because no subjects in Part 2, and only one subject in Part 1, had an objective response the analysis of duration of response was not calculated.
Secondary
Progression Free Survival
Progression-free survival is defined as the number of days from study day 1 (first dose of investigational product) to the first observation of disease progression (by modified RECIST; or clinical progression, whichever came first) or death due to any cause. Disease progression by RECIST is defined as at least a 20% increase in the sum of diameters of target lesions in reference to the smallest sum on study and an absolute increase of at least 5 mm; the appearance of any new lesions is also considered progression.
Time frame: Time from first dose up to 24 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1 Cohort 1 | Progression Free Survival | 1.4 months |
| Part 1 Cohort 2 | Progression Free Survival | 4.9 months |
| Part 1 Cohort 3 | Progression Free Survival | 1.3 months |
| Part 2 Cohort 1 | Progression Free Survival | 1.6 months |
| Part 2 Cohort 2 | Progression Free Survival | 3.3 months |
| Part 2 Cohort 3 | Progression Free Survival | 1.5 months |
| Part 2 Cohort 4 | Progression Free Survival | 1.4 months |
| Part 2 Cohort 5 | Progression Free Survival | 2.8 months |
| Part 2 Cohort 6 | Progression Free Survival | 1.3 months |
Secondary
Time to Response
Time to response is the time from study day 1 to the first observation of an objective response. Subjects without an objective response are excluded from the analysis of this endpoint. Objective response is defined as a tumor response assessment of either complete response or partial response per modified Response Evaluation Criteria in Solid Tumors (RECIST) and will be determined based on the Investigator-reported assessment only for subjects with measurable disease at baseline. Per RECIST v 1.1: a complete response is the disappearance of all target lesions; a partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: Time from first dose up to 24 months
Population: Because no subjects in Part 2, and only one subject in Part 1, had an objective response the analyses of time to response was not calculated.
Secondary
To Evaluate Anti-AMG 655 Antibody Formation and Anti-AMG 479 Antibody Formation
Time frame: Time from first dose up to 24 months
Population: Antibody Population = All subjects in the full analysis set tested for antibodies during the study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1 Cohort 1 | To Evaluate Anti-AMG 655 Antibody Formation and Anti-AMG 479 Antibody Formation | AMG 479 - Binding antibody positive at any time | 0 Participants |
| Part 1 Cohort 1 | To Evaluate Anti-AMG 655 Antibody Formation and Anti-AMG 479 Antibody Formation | AMG 655 - Binding antibody positive at any time | 0 Participants |
| Part 1 Cohort 1 | To Evaluate Anti-AMG 655 Antibody Formation and Anti-AMG 479 Antibody Formation | AMG 655 - Neutralizing antibody positive at any time | 0 Participants |
| Part 1 Cohort 1 | To Evaluate Anti-AMG 655 Antibody Formation and Anti-AMG 479 Antibody Formation | AMG 479 - Neutralizing antibody positive at any time | 0 Participants |
| Part 1 Cohort 2 | To Evaluate Anti-AMG 655 Antibody Formation and Anti-AMG 479 Antibody Formation | AMG 655 - Neutralizing antibody positive at any time | 0 Participants |
| Part 1 Cohort 2 | To Evaluate Anti-AMG 655 Antibody Formation and Anti-AMG 479 Antibody Formation | AMG 479 - Binding antibody positive at any time | 0 Participants |
| Part 1 Cohort 2 | To Evaluate Anti-AMG 655 Antibody Formation and Anti-AMG 479 Antibody Formation | AMG 479 - Neutralizing antibody positive at any time | 0 Participants |
| Part 1 Cohort 2 | To Evaluate Anti-AMG 655 Antibody Formation and Anti-AMG 479 Antibody Formation | AMG 655 - Binding antibody positive at any time | 0 Participants |
| Part 1 Cohort 3 | To Evaluate Anti-AMG 655 Antibody Formation and Anti-AMG 479 Antibody Formation | AMG 655 - Neutralizing antibody positive at any time | 0 Participants |
| Part 1 Cohort 3 | To Evaluate Anti-AMG 655 Antibody Formation and Anti-AMG 479 Antibody Formation | AMG 479 - Binding antibody positive at any time | 0 Participants |
| Part 1 Cohort 3 | To Evaluate Anti-AMG 655 Antibody Formation and Anti-AMG 479 Antibody Formation | AMG 655 - Binding antibody positive at any time | 0 Participants |
| Part 1 Cohort 3 | To Evaluate Anti-AMG 655 Antibody Formation and Anti-AMG 479 Antibody Formation | AMG 479 - Neutralizing antibody positive at any time | 0 Participants |
| Part 2 Cohort 1 | To Evaluate Anti-AMG 655 Antibody Formation and Anti-AMG 479 Antibody Formation | AMG 655 - Binding antibody positive at any time | 0 Participants |
| Part 2 Cohort 1 | To Evaluate Anti-AMG 655 Antibody Formation and Anti-AMG 479 Antibody Formation | AMG 479 - Neutralizing antibody positive at any time | 0 Participants |
| Part 2 Cohort 1 | To Evaluate Anti-AMG 655 Antibody Formation and Anti-AMG 479 Antibody Formation | AMG 655 - Neutralizing antibody positive at any time | 0 Participants |
| Part 2 Cohort 1 | To Evaluate Anti-AMG 655 Antibody Formation and Anti-AMG 479 Antibody Formation | AMG 479 - Binding antibody positive at any time | 2 Participants |
| Part 2 Cohort 2 | To Evaluate Anti-AMG 655 Antibody Formation and Anti-AMG 479 Antibody Formation | AMG 655 - Neutralizing antibody positive at any time | 0 Participants |
| Part 2 Cohort 2 | To Evaluate Anti-AMG 655 Antibody Formation and Anti-AMG 479 Antibody Formation | AMG 655 - Binding antibody positive at any time | 0 Participants |
| Part 2 Cohort 2 | To Evaluate Anti-AMG 655 Antibody Formation and Anti-AMG 479 Antibody Formation | AMG 479 - Binding antibody positive at any time | 0 Participants |
| Part 2 Cohort 2 | To Evaluate Anti-AMG 655 Antibody Formation and Anti-AMG 479 Antibody Formation | AMG 479 - Neutralizing antibody positive at any time | 0 Participants |
| Part 2 Cohort 3 | To Evaluate Anti-AMG 655 Antibody Formation and Anti-AMG 479 Antibody Formation | AMG 479 - Neutralizing antibody positive at any time | 0 Participants |
| Part 2 Cohort 3 | To Evaluate Anti-AMG 655 Antibody Formation and Anti-AMG 479 Antibody Formation | AMG 479 - Binding antibody positive at any time | 0 Participants |
| Part 2 Cohort 3 | To Evaluate Anti-AMG 655 Antibody Formation and Anti-AMG 479 Antibody Formation | AMG 655 - Binding antibody positive at any time | 0 Participants |
| Part 2 Cohort 3 | To Evaluate Anti-AMG 655 Antibody Formation and Anti-AMG 479 Antibody Formation | AMG 655 - Neutralizing antibody positive at any time | 0 Participants |
| Part 2 Cohort 4 | To Evaluate Anti-AMG 655 Antibody Formation and Anti-AMG 479 Antibody Formation | AMG 479 - Binding antibody positive at any time | 0 Participants |
| Part 2 Cohort 4 | To Evaluate Anti-AMG 655 Antibody Formation and Anti-AMG 479 Antibody Formation | AMG 655 - Neutralizing antibody positive at any time | 0 Participants |
| Part 2 Cohort 4 | To Evaluate Anti-AMG 655 Antibody Formation and Anti-AMG 479 Antibody Formation | AMG 655 - Binding antibody positive at any time | 1 Participants |
| Part 2 Cohort 4 | To Evaluate Anti-AMG 655 Antibody Formation and Anti-AMG 479 Antibody Formation | AMG 479 - Neutralizing antibody positive at any time | 0 Participants |
| Part 2 Cohort 5 | To Evaluate Anti-AMG 655 Antibody Formation and Anti-AMG 479 Antibody Formation | AMG 655 - Binding antibody positive at any time | 0 Participants |
| Part 2 Cohort 5 | To Evaluate Anti-AMG 655 Antibody Formation and Anti-AMG 479 Antibody Formation | AMG 479 - Binding antibody positive at any time | 0 Participants |
| Part 2 Cohort 5 | To Evaluate Anti-AMG 655 Antibody Formation and Anti-AMG 479 Antibody Formation | AMG 655 - Neutralizing antibody positive at any time | 0 Participants |
| Part 2 Cohort 5 | To Evaluate Anti-AMG 655 Antibody Formation and Anti-AMG 479 Antibody Formation | AMG 479 - Neutralizing antibody positive at any time | 0 Participants |
| Part 2 Cohort 6 | To Evaluate Anti-AMG 655 Antibody Formation and Anti-AMG 479 Antibody Formation | AMG 479 - Neutralizing antibody positive at any time | 0 Participants |
| Part 2 Cohort 6 | To Evaluate Anti-AMG 655 Antibody Formation and Anti-AMG 479 Antibody Formation | AMG 655 - Binding antibody positive at any time | 0 Participants |
| Part 2 Cohort 6 | To Evaluate Anti-AMG 655 Antibody Formation and Anti-AMG 479 Antibody Formation | AMG 655 - Neutralizing antibody positive at any time | 0 Participants |
| Part 2 Cohort 6 | To Evaluate Anti-AMG 655 Antibody Formation and Anti-AMG 479 Antibody Formation | AMG 479 - Binding antibody positive at any time | 0 Participants |
Secondary
To Evaluate the Concentration Level of AMG 479
Median, minimum, and maximum concentration of AMG 479 at specified time points.
Time frame: Cycle 1 Day 1 end of infusion; Cycle 3 Day 1 end of infusion (each cycle is 28 days, each infusion is up to 1 hour)
Population: PK population = All subjects in the full analysis set who underwent blood sampling for PK evaluation during the study.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1 Cohort 1 | To Evaluate the Concentration Level of AMG 479 | Cycle 1-End of infusion | 272 μg/mL |
| Part 1 Cohort 1 | To Evaluate the Concentration Level of AMG 479 | Cycle 3-End of Infusion | 308 μg/mL |
| Part 1 Cohort 2 | To Evaluate the Concentration Level of AMG 479 | Cycle 1-End of infusion | 268 μg/mL |
| Part 1 Cohort 3 | To Evaluate the Concentration Level of AMG 479 | Cycle 3-End of Infusion | 338 μg/mL |
| Part 1 Cohort 3 | To Evaluate the Concentration Level of AMG 479 | Cycle 1-End of infusion | 303 μg/mL |
| Part 2 Cohort 1 | To Evaluate the Concentration Level of AMG 479 | Cycle 1-End of infusion | 215 μg/mL |
| Part 2 Cohort 1 | To Evaluate the Concentration Level of AMG 479 | Cycle 3-End of Infusion | 404 μg/mL |
| Part 2 Cohort 2 | To Evaluate the Concentration Level of AMG 479 | Cycle 1-End of infusion | 297 μg/mL |
| Part 2 Cohort 3 | To Evaluate the Concentration Level of AMG 479 | Cycle 3-End of Infusion | 262 μg/mL |
| Part 2 Cohort 3 | To Evaluate the Concentration Level of AMG 479 | Cycle 1-End of infusion | 227 μg/mL |
| Part 2 Cohort 4 | To Evaluate the Concentration Level of AMG 479 | Cycle 1-End of infusion | 236 μg/mL |
| Part 2 Cohort 4 | To Evaluate the Concentration Level of AMG 479 | Cycle 3-End of Infusion | 249 μg/mL |
| Part 2 Cohort 5 | To Evaluate the Concentration Level of AMG 479 | Cycle 1-End of infusion | 324 μg/mL |
| Part 2 Cohort 5 | To Evaluate the Concentration Level of AMG 479 | Cycle 3-End of Infusion | 323 μg/mL |
| Part 2 Cohort 6 | To Evaluate the Concentration Level of AMG 479 | Cycle 3-End of Infusion | 365 μg/mL |
| Part 2 Cohort 6 | To Evaluate the Concentration Level of AMG 479 | Cycle 1-End of infusion | 254 μg/mL |
Secondary
To Evaluate the Concentration Level of AMG 655
Median, minimum, and maximum concentration of AMG 655 at specified time points.
Time frame: Cycle 1 Day 1 end of infusion; Cycle 3 Day 1 end of infusion (each cycle is 28 days, each infusion is up to 1 hour)
Population: PK population = All subjects in the full analysis set who underwent blood sampling for PK evaluation during the study.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1 Cohort 1 | To Evaluate the Concentration Level of AMG 655 | Cycle 3-End of infusion | 23.6 μg/mL |
| Part 1 Cohort 1 | To Evaluate the Concentration Level of AMG 655 | Cycle 1-End of Infusion | 17.5 μg/mL |
| Part 1 Cohort 2 | To Evaluate the Concentration Level of AMG 655 | Cycle 1-End of Infusion | 59.0 μg/mL |
| Part 1 Cohort 2 | To Evaluate the Concentration Level of AMG 655 | Cycle 3-End of infusion | 62.3 μg/mL |
| Part 1 Cohort 3 | To Evaluate the Concentration Level of AMG 655 | Cycle 1-End of Infusion | 313 μg/mL |
| Part 1 Cohort 3 | To Evaluate the Concentration Level of AMG 655 | Cycle 3-End of infusion | 302 μg/mL |
| Part 2 Cohort 1 | To Evaluate the Concentration Level of AMG 655 | Cycle 3-End of infusion | 448 μg/mL |
| Part 2 Cohort 1 | To Evaluate the Concentration Level of AMG 655 | Cycle 1-End of Infusion | 244 μg/mL |
| Part 2 Cohort 2 | To Evaluate the Concentration Level of AMG 655 | Cycle 1-End of Infusion | 266 μg/mL |
| Part 2 Cohort 3 | To Evaluate the Concentration Level of AMG 655 | Cycle 1-End of Infusion | 240 μg/mL |
| Part 2 Cohort 3 | To Evaluate the Concentration Level of AMG 655 | Cycle 3-End of infusion | 311 μg/mL |
| Part 2 Cohort 4 | To Evaluate the Concentration Level of AMG 655 | Cycle 1-End of Infusion | 224 μg/mL |
| Part 2 Cohort 4 | To Evaluate the Concentration Level of AMG 655 | Cycle 3-End of infusion | 253 μg/mL |
| Part 2 Cohort 5 | To Evaluate the Concentration Level of AMG 655 | Cycle 3-End of infusion | 423 μg/mL |
| Part 2 Cohort 5 | To Evaluate the Concentration Level of AMG 655 | Cycle 1-End of Infusion | 327 μg/mL |
| Part 2 Cohort 6 | To Evaluate the Concentration Level of AMG 655 | Cycle 1-End of Infusion | 247 μg/mL |
| Part 2 Cohort 6 | To Evaluate the Concentration Level of AMG 655 | Cycle 3-End of infusion | 371 μg/mL |